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<span class="paragraphSection">This is a correction to: Elias Gerges <span style="font-style:italic;">et al.</span>, Association of serum interferon alpha-2a levels with disease severity and prognosis in systemic sclerosis, <span style="font-style:italic;">Rheumatology</span>, 2024; <a href="https://doi.org/10.1093/rheumatology/keae546">https://doi.org/10.1093/rheumatology/keae546</a></span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Objective</div>To assess the phenotypic characteristics of the patients carrying variants of uncertain significance (VUS) in the Mediterranean fever (<span style="font-style:italic;">MEFV</span>) gene.<div class="boxTitle">Methods</div>The study included patients carrying only VUS in the <span style="font-style:italic;">MEFV</span> gene. Patients were excluded if they did not meet the paediatric criteria for familial Mediterranean fever (FMF). Patients were assigned to homozygous, compound heterozygous or heterozygous groups according to their genotype. Additionally, analyses were conducted based on specific genotypes.<div class="boxTitle">Results</div>A total of 2326 <span style="font-style:italic;">MEFV</span> gene records were reviewed. Of these, 310 (F: 152/M: 158) met the inclusion criteria for analysis. The mean age at diagnosis and symptom onset was 7.51 ± 3.9 and 6.03 ± 3.86 years, respectively. Among the patients, 75.5% had a single variant, 17.1% were compound heterozygous, and 7.4% were homozygous. The common VUS alleles accounted for 93% of the cohort: E148Q (65.7%), P369S (15.6%), R408Q (7.6%) and A744S (4.1%). Most cases exhibited mild disease severity, while those with multiple variants were more likely to experience moderate disease severity. Patients with a homozygous allele had a higher mean number of annual attacks (11.2/year), a higher Pras severity score (5.86) and a greater proportion of moderate disease severity (56.5%). The most common clinical manifestations were abdominal pain (90.6%), fever (84.2%) and arthralgia (58.7%).<div class="boxTitle">Conclusion</div>Individuals with VUS variants in the <span style="font-style:italic;">MEFV</span> gene may present with a classic FMF phenotype characterized by mild to moderate disease activity. Patients carrying various VUS genotypes in the <span style="font-style:italic;">MEFV</span> gene exhibit comparable clinical features with some degree of variation.</span>
<span class="paragraphSection"><div class="boxedTextSection">Rheumatology key message<ul><li class="bullet">Combination advanced therapy is infrequently used for spondyloarthritis and psoriatic arthritis in UK rheumatology practice.</li></ul></div></span>
<span class="paragraphSection"><strong>This editorial refers to ‘Impact of structural severity on outcomes in knee osteoarthritis: an analysis of data from phase 2 and phase 3 lorecivivint clinical trials’ by Jeyanesh Tambiah <span style="font-style:italic;">et al.</span> 2025;64:2583–90.</strong></span>
<span class="paragraphSection">Psoriasis and Psoriatic Arthritis Alliance10.13039/501100004248National Institute for Health Research10.13039/501100000272Academic Clinical FellowshipACF-2024–02-010National Institute for Health Research10.13039/501100000272Versus Arthritis10.13039/501100012041211732175421755NIHR10.13039/100006662Manchester Biomedical Research Centre10.13039/100014653NIHR203308</span>
<span class="paragraphSection">A 72-year-old woman with a 19-year history of seropositive rheumatoid arthritis (RA) was referred to our department for anterior chest pain that had persisted for 1 year. Despite treatment with etanercept and methotrexate for 17 years, the patient did not achieve remission over the past 2 years. She had no history of trauma. Physical examinations revealed a protrusion on the anterior sternum, and swelling and deformity in some finger joints. Positron emission tomography–computed tomography revealed a mass destructing manubriosternal joint (MSJ) with increased uptake of fluorodeoxyglucose (<a href="#keaf080-F1" class="reflinks">Fig. 1A</a> and <a href="#keaf080-F1" class="reflinks">B</a>). Incisional biopsy of the mass revealed a rheumatoid nodule (<a href="#keaf080-F1" class="reflinks">Fig. 1C</a>). No evidence of malignancy or infection was detected. A diagnosis of MSJ destruction with rheumatoid nodule was made. Etanercept was switched to upadacitinib. After 6 months, the RA and rheumatoid nodule significantly improved.</span>
<span class="paragraphSection">An otherwise healthy woman in her 70s presented with a 4-year history of disfiguring facial lesions. Physical examination revealed a large, indurated, erythematous plaque with prominent telangiectasias extending from the nasal bridge towards the medial canthus and left cheek (<a href="#keaf082-F1" class="reflinks">Fig. 1A</a>). She reported no itching or pain and denied symptoms such as dyspnea, cough, ocular discomfort, palpitations, or epistaxis. Histopathological examination of a skin biopsy showed superficial and deep dermal non-caseating granulomas. The laboratory results were unremarkable, with normal levels of angiotensin-converting enzyme, serum calcium, and urine calcium. Comprehensive examinations, including chest radiographs, pulmonary function tests, ECGs, and ophthalmologic evaluations, showed no abnormalities. The patient was diagnosed with an angiolupoid variant of isolated cutaneous sarcoidosis. Angiolupoid sarcoidosis typically presents as an erythematous plaque with prominent telangiectasias on the central face. Differential diagnoses include large basal cell carcinoma and rosacea. Angiolupoid sarcoidosis carries a high risk of ocular, pulmonary and lymphatic involvement, highlighting the need for prompt diagnosis and treatment [<a href="#keaf082-B1" class="reflinks">1</a>]. The patient received topical and intralesional CSs, oral CSs, doxycycline, HCQ, and MTX, but the response remained poor. She was subsequently treated with tofacitinib alone at a dose of 10 mg/day, resulting in the resolution of the erythema and induration after 8 months (<a href="#keaf082-F1" class="reflinks">Fig. 1B</a>). The patient gave consent for the publication of this case study.</span>
<span class="paragraphSection">University of Wisconsin-Madison10.13039/100007015Institute for Clinical and Translational Research10.13039/100005902National Institutes of Health10.13039/100000002National Center for Advancing Translational Sciences10.13039/100006108Clinical and Translational ScienceUL1TR002373NIH10.13039/1000000021K23AR084608-01</span>
<span class="paragraphSection"><span style="text-transform:lowercase;font-variant:small-caps;">Dear Editor</span>, We have read the article published by Garg <span style="font-style:italic;">et al.</span> [<a href="#keaf059-B1" class="reflinks">1</a>] with great interest. The authors evaluated renal arteriosclerosis in kidney biopsies of patients with lupus nephritis (LN) and examined its associations with the occurrence of atherosclerotic cardiovascular (CV) disease. They found that renal arteriosclerosis (>25%), high area deprivation index (>80) and use of angiotensin-converting enzyme inhibitors at the diagnosis of LN were associated with the risk of atherosclerotic CV disease.</span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Objectives</div>GCA is a granulomatous vasculitis affecting large vessels, leading to intimal occlusion accompanied by the accumulation of myofibroblasts. Histopathologically, GCA is characterized by destruction of the tunica media and hypertrophy of the intima with invasion of activated CD4+ T cells, macrophages and multinucleated giant cells (MNGCs). Despite these well-defined histopathological features, the molecular pathology of GCA has largely remained elusive. We aimed to characterize the pathologic features of GCA at the molecular level.<div class="boxTitle">Methods</div>To identify key molecules involved in GCA pathogenesis, we conducted genome-wide gene expression profiling on arterial lesions obtained through temporal artery biopsy of 16 patients who had not received any prior treatment. The resulting data were examined to reveal specific pathways and genes, and some of the molecules were followed up by immunohistochemistry.<div class="boxTitle">Results</div>Our analysis revealed a unique gene expression pattern in GCA lesions, including enrichment of immune cells and phagocytic pathways related to microglia and osteoclasts. Subsequent immunohistochemistry analysis identified the presence of MMP12 (macrophage elastase), HLA-DRA, and phagocytosis- and osteoclast-associated molecules in infiltrating macrophages and MNGCs. Additionally, we discovered LRRC15-expressing cells in the tunica intima, suggesting a myofibroblast subpopulation that suppresses cytotoxic CD8+ T cells. These molecules were upregulated in other granulomatous diseases affecting not only arteries but also lymph nodes.<div class="boxTitle">Conclusion</div>Our study revealed novel molecules associated with the pathological features of GCA, providing a foundation for better understanding of GCA pathogenesis and development of targeted therapeutic strategies.</span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Objectives</div>To investigate the occurrence and dynamics of secretory component-containing antibodies towards citrullinated proteins (SC ACPA) in plasma from pre-symptomatic individuals subsequently developing rheumatoid arthritis (RA).<div class="boxTitle">Methods</div>We studied 319 individuals who had donated plasma prior to RA onset (median predating time 4.7 years), whereof 181 also donated samples after diagnosis. One hundred individuals were randomly selected from the same biobank cohorts to serve as controls. SC ACPA, total secretory IgA (TSIgA) and IgG ACPA were analysed in plasma by enzyme-linked immunoassays.<div class="boxTitle">Results</div>Circulating SC ACPA levels in pre-symptomatic individuals and RA patients were significantly increased compared with controls [median (interquartile range) 108 (108), 179 (248) and 12.5 (537) AU/ml, respectively; <span style="font-style:italic;">P</span> < 0.001], and SC ACPA levels in RA patients were significantly increased compared with pre-symptomatic individuals (<span style="font-style:italic;">P</span> <span style="font-style:italic;"><</span> 0.001). SC ACPA increased, in terms of both levels and proportion of positive samples, closer to symptom onset and diagnosis. TSIgA was not elevated compared with controls either during the pre-dating time or after diagnosis. The earliest detected SC ACPA positive sample was 9 years before symptom onset, as compared with 11 years for IgG ACPA. Only two pre-dating samples were positive for SC ACPA and negative for IgG ACPA.<div class="boxTitle">Conclusions</div>Circulating SC ACPA responses arise and magnify during the asymptomatic phase of disease development in a subgroup of RA patients. This suggests mucosal involvement prior to both symptom onset and subsequent arthritis. As mirrored in the circulation, however, SC ACPA does not seem to precede the IgG ACPA response.</span>
<span class="paragraphSection"><div class="boxedTextSection">Rheumatology key message<ul><li class="bullet">Polyserositis can be an early manifestation of undifferentiated connective tissue disease in patients</li></ul></div></span>
<span class="paragraphSection"><div class="boxedTextSection">Rheumatology key message<ul><li class="bullet">A first description of a paediatric case of Susac Syndrome with spinal cord involvement.</li></ul></div></span>
<span class="paragraphSection">This is a correction to: Till Uhlig, Lars F Karoliussen, Joe Sexton, Sella A Provan, Espen A Haavardsholm, Nicola Dalbeth, Hilde Berner Hammer, Non-adherence to urate lowering therapy in gout after 5 years is related to poor outcomes: results from the NOR-Gout study, <span style="font-style:italic;">Rheumatology</span>, 2024, keae514, <a href="https://doi.org/10.1093/rheumatology/keae514">https://doi.org/10.1093/rheumatology/keae514</a></span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Objective</div>To explore thresholds for the Psoriatic Arthritis (PsA) Impact of Disease questionnaire (PsAID12) score against disease activity measures in an observational setting, in patients with PsA.<div class="boxTitle">Methods</div>The baseline data from the ReFlaP observational, prospective, multicentre and international study were used (NCT03119805). Cutoffs for PsAID12 were determined against disease activity scores, defining disease impact states (i.e. remission, low impact, moderate impact and high impact). Statistics used to assess the optimal cutoff point included Youden’s index and the 75th percentile method, with external anchors (i.e. Disease Activity index for Psoriatic Arthritis [DAPSA], very low disease activity [VLDA]/minimal disease activity [MDA] and single questions for both patients and physicians) serving as gold standards. The diagnostic performance of these cutoffs was evaluated using receiver operating characteristic (ROC) curve analyses.<div class="boxTitle">Results</div>A total of 410 patients were analysed. Mean (<span style="text-transform:lowercase;font-variant:small-caps;">s</span>.<span style="text-transform:lowercase;font-variant:small-caps;">d</span>.) PsAID12 score was 3.4 (2.5). The prevalence of remission varied between 12.4% and 36.1%, while low disease activity ranged from 37.8% to 59.8%. PsAID12 performed well against external anchors, with high areas under the ROC curves ranging from 0.75 to 0.94. Using the DAPSA as external anchor, the proposed PsAID12 cutoffs were <1.7 for remission, ≥1.7 to ≤3.1 for low impact, >3.1 to <4.8 for moderate impact and ≥4.8 for high impact. Compared with composite scores, patient and physician opinions performed less stringently.<div class="boxTitle">Conclusion</div>This study established cutoffs for PsAID12 in a clinical practice observational population, corresponding to remission and varying levels of disease impact. However, these proposed cutoffs need further validation, and an expert consensus is essential to confirm the most accurate thresholds for future use.</span>
<span class="paragraphSection"><strong>This editorial refers to Distinct clinical trajectories of gastrointestinal progression among patients with systemic sclerosis, by Perin <span style="font-style:italic;">et al</span>. <span style="font-style:italic;">Rheumatology</span>, 2025;64:2766–74.</strong></span>
<span class="paragraphSection"><div class="boxedTextSection">Rheumatology key message<ul><li class="bullet">DAH as a cause of dyspnoea should be ruled out in JDM.</li></ul></div></span>
<span class="paragraphSection"><div class="boxedTextSection">Rheumatology key message<ul><li class="bullet">Remission of lymphoma and rheumatoid arthritis with CD19 CAR T-cell therapy</li></ul></div></span>
<span class="paragraphSection"><strong>This editorial refers to ‘Temporal and regional variation in the use of biologic and targeted synthetic DMARDs for rheumatoid arthritis: a nationwide cohort study’, by Mark D. Russell <span style="font-style:italic;">et al</span>., 2025;64:2432–41.</strong></span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Objectives</div>To summarize and evaluate Cochrane reviews of pharmacological therapies for adults with fibromyalgia syndrome (FMS) pain.<div class="boxTitle">Methods</div>Systematic search of Cochrane Database of Systematic Reviews to May 2024. Generic quality assessment used AMSTAR-2 criteria, validity checks of potentially critical factors in evaluation of analgesic efficacy and assessment of susceptibility of results to publication bias. Pain outcomes were participant-reported pain relief of ≥30% or ≥50%, or PGIC much or very much improved.<div class="boxTitle">Results</div>Twenty-one reviews (87 trials, 17 631 patients) were included. All rated moderate (15) or high-quality (6) using AMSTAR-2 and at least seven of eight critical pain criteria were met by 13 of 21 reviews. Diagnosis of FMS used recognized criteria. Seven reviews found no trials (carbamazepine, clonazepam, lamotrigine, phenytoin, oxycodone, topiramate or valproate), seven had limited and inadequate data (antipsychotics, cannabinoids, combination therapy, gabapentin, lacosamide, monoamine oxidase inhibitors, NSAIDs) and two were subject to publication bias (amitriptyline, SSRI). Mirtazapine had moderate evidence of no effect. Duloxetine, milnacipran and pregabalin had moderate/good evidence of substantial pain relief for 4–12 weeks in around 1 in 10 adults with moderate or severe FMS pain, without evidence of efficacy beyond six months. Serious adverse events were no more common than with placebo. There was no evidence about who might benefit or experience adverse events. There was no substantial efficacy evidence for other medicines.<div class="boxTitle">Conclusions</div>Duloxetine, milnacipran and pregabalin had good evidence that about 1 person in 10 with moderate or severe pain experienced pain intensity reduction by at least 50%.</span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Objectives</div>The specificity of US for enthesitis in PsA is unclear. The objective was to analyse the specificity of US enthesitis in Mode B and using power Doppler for the diagnosis of PsA through a systematic review with meta-analysis.<div class="boxTitle">Methods</div>Systematic review in PubMed 2010 to June 2023 of studies of adult patients with confirmed PsA with or without a control group of non-PsA patients, reporting information on US enthesitis. Data were analysed on (i) the prevalence of US enthesitis (presence of at least one enthesitis) in PsA patients and non-PsA patients, (ii) specificity and sensitivity of US enthesitis and then specifically power Doppler for PsA diagnosis and (iii) most specific localizations of enthesitis in PsA patients. Pooled percentages and means were evaluated using univariate random effects meta-analysis.<div class="boxTitle">Results</div>In 76 articles, 5927 patients with PsA were compared with 3423 controls (59.0% of whom had psoriasis). The prevalence of US enthesitis was 73.7% (95% CI 56.6–90.9%) in PsA patients <span style="font-style:italic;">vs</span> 12.6% (2.6–22.3%) in controls. The pooled specificity and sensitivity of Mode B US were 73.2% (59.3–87.0%) and 62.1% (47.9–76.4%); and of power Doppler, were 97.9% (96.5–99.5%) and 14.7% (8.2–21.2%), respectively. The site most frequently involved in PsA but not in controls was the Achilles tendon, in which erosions and power Doppler activity were most discriminant.<div class="boxTitle">Conclusion</div>In this systematic review, US enthesitis was highly prevalent in PsA patients. Evidencing enthesitis by US was found to be reasonably specific and could contribute to the diagnosis of PsA; power Doppler was highly specific, however it was rarely present.</span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Objective</div>Patients with lupus nephritis (LN), including those below age 50, face significantly higher risk of atherosclerotic cardiovascular disease (ASCVD) <span style="font-style:italic;">vs</span> peers. This highlights the need for identifying specific ASCVD risk factors in LN. Renal arteriosclerosis in kidney biopsies (subclinical arteriosclerosis) may be able to predict future clinical ASCVD events. However, renal arteriosclerosis is under-reported in LN biopsies and is not taken into consideration when ASCVD risk is calculated. Therefore, we aimed to systematically grade renal arteriosclerosis in kidney biopsies at LN diagnosis and examined associations with 10-year and 20-year ASCVD occurrence.<div class="boxTitle">Methods</div>Adults with biopsy-proven LN were included. Clinical ASCVD, including fatal and non-fatal events, were adjudicated. Utilizing standard Banff grading criteria, all biopsies at LN diagnosis were re-read to grade renal arteriosclerosis. Covariables (e.g. socio-demographics, comorbidities, med exposure) were abstracted. Using Cox models, factors (including renal arteriosclerosis) associated with 10-year and 20-year clinical ASCVD were examined.<div class="boxTitle">Results</div>Among 209 patients, 36 and 49 clinical ASCVD occurred within 10 and 20 years. Renal arteriosclerosis (>25%) was associated with 3× higher 10-year ASCVD. High area deprivation index (>80) and longer angiotensin converting enzyme inhibitor (ACEi) exposure were associated with 4× higher and 0.65× lower ASCVD occurrence. Adding renal arteriosclerosis >25% improved model performance for 10-year ASCVD risk estimation from 65% to 80%. Similar associations were seen with 20-year ASCVD.<div class="boxTitle">Conclusion</div>Renal arteriosclerosis >25%, area deprivation and ACEi exposure could inform ASCVD risk stratification in LN. Prospective studies should validate findings and inform clinical use.</span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Objectives</div>The clinical manifestations of dermatomyositis (DM) are diverse, nailfold video-capillaroscopy (NVC) can reflect microangiopathy, a process believed to contribute significantly to the clinical manifestations of DM. We aimed to explore the distinctive alterations and implications of nailfold capillary for evaluating disease progression in individuals with DM.<div class="boxTitle">Methods</div>We gathered clinical data from 76 DM patients who underwent NVC in the Affiliated Hospital of Nantong University between September 2017 and September 2022. Additionally, we recruited 26 anti-synthase antibody syndrome (ASS) patients and 33 systemic sclerosis (SSc) patients as controls. Utilizing an unsupervised machine learning method (hierarchical clustering analysis) to categorized patients based on NVC results and compared clinical characteristics and survival outcomes. The follow-up period ended in December 2022.<div class="boxTitle">Results</div>Anomalous NVC patterns were detected in 73.7% of the 76 DM patients and manifested as diminished capillary density and abnormal capillary morphology. Patients displaying abnormal NVC findings exhibited a significantly higher prevalence of Raynaud's phenomenon and a greater likelihood of being managed with triple combination therapy. Compared with SSc patients, milder NVC changes were observed in patients with DM, nonetheless, NVC abnormalities were more prominent in DM patients when contrasted with individuals with ASS. Furthermore, the patients were classified into two different clusters according to NVC data. Patients in cluster 1 were more likely to develop interstitial lung disease (ILD). Survival outcomes did not differ significantly between the two clusters.<div class="boxTitle">Conclusion</div>DM patients can experience varying degrees of aberrant NVC patterns, which can impact ILD risk and warrant clinical vigilance.</span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Objectives</div>To compare treatment outcomes in patients with late-onset RA (LORA) and younger-onset RA (YORA).<div class="boxTitle">Methods</div>We analyzed patients diagnosed with early RA (disease duration < 2 years) between 2000 and 2016 in the Institute of Rheumatology, Rheumatoid Arthritis (IORRA) cohort. Patients were categorized into LORA (onset at ≥65 years) and YORA (onset at <65 years). The primary outcomes were changes in Clinical Disease Activity Index (CDAI) and Japanese version of the Health Assessment Questionnaire (J-HAQ) at Year 5. The secondary outcomes included the incidence of prespecified adverse events.<div class="boxTitle">Results</div>Methotrexate, biological disease-modifying anti-rheumatic drugs, and glucocorticoids were used in 70.6, 8.4 and 38.0% of the LORA group (<span style="font-style:italic;">n</span> = 813, median age: 71 years), and 81.6, 19.4 and 32.0% of the YORA group (<span style="font-style:italic;">n</span> = 2457, median age: 51 years). Both groups exhibited significant initial improvements in CDAI and J-HAQ scores. At Year 5, mean CDAI scores were 4.39 and 4.03 for the LORA and YORA groups, respectively. J-HAQ score for YORA remained stable below 0.5 after Year 2, whereas that for LORA worsened progressively. At Year 5, mean J-HAQ scores were 0.56 for LORA and 0.33 for YORA. Patients with LORA had a higher incidence of adverse events, with adjusted hazard ratios of 4.70 for death and 2.58 for malignancy.<div class="boxTitle">Conclusions</div>Patients with LORA and YORA exhibited similar improvements in disease activity over 5 years; however, those with LORA demonstrated a more pronounced decline in physical function.</span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Objectives</div>Convolutional neural networks (CNNs) are increasingly used to classify medical images, but few studies utilize smartphone photographs. The objective of this study was to assess CNNs for differentiating patients from controls and detecting joint inflammation.<div class="boxTitle">Methods</div>We included consecutive patients with early inflammatory arthritis and healthy controls, all examined by a rheumatologist (15% by two). Standardized hand photographs of the hands were taken, anonymized and cropped around joints. Pre-trained CNN models were fine-tuned on our dataset (80% training; 20% test set). We used an Inception-ResNet-v2 backbone CNN modified for two class outputs (patient <span style="font-style:italic;">vs</span> control) on uncropped photos. Separate Inception-ResNet-v2 CNNs were trained on cropped photos of middle finger proximal interphalangeal (MFPIP), index finger proximal interphalangeal (IFPIP) and wrist. We report accuracy, sensitivity, specificity and area under the receiver operating characteristic curve (AUC).<div class="boxTitle">Results</div>We analysed 800 hands from 200 controls (mean age 37.8 years) and 200 patients (mean age 49 years). Two rheumatologists showed 0.89 concordance. The wrist was commonly involved (173/400) followed by the MFPIP (134) and IFPIP (128). The screening CNN achieved 99% accuracy and specificity and 98% sensitivity in predicting a patient compared with controls. Joint-specific CNN accuracy, sensitivity, specificity and AUC were as follows: wrist (75%, 92%, 72% and 0.86, respectively), IFPIP (73%, 89%, 72% and 0.88, respectively) and MFPIP (71%, 91%, 70% and 0.87, respectively).<div class="boxTitle">Conclusion</div>Computer vision distinguishes patients and controls using smartphone photographs, showing promise as a screening tool. Future research will focus on validating findings in diverse populations and other joints and integrating this technology into clinical workflows.</span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Objective</div>To develop and validate a patient-reported definition of acute calcium pyrophosphate (CPP) crystal arthritis in people with crystal-proven CPP deposition (CPPD) disease.<div class="boxTitle">Methods</div>Consecutive patients with crystal-proven CPPD disease from seven centres across four countries were enrolled in a cross-sectional study. In each centre, patient-reported outcomes on the features of acute CPP crystal arthritis were collected. The expert opinion of an independent rheumatologist was the reference standard. We developed definitions based on multivariable logistic regression model with backward selection of predictors and classification and regression tree (CART) approaches.<div class="boxTitle">Results</div>Two hundred and forty-six patients [mean age 73.2 years (<span style="text-transform:lowercase;font-variant:small-caps;">s</span>.<span style="text-transform:lowercase;font-variant:small-caps;">d</span>. 10.7), 65.9% female] were enrolled. At the time of the assessment, acute CPP crystal arthritis was diagnosed in 96/246 (39.0%) participants.Patient-reported joint warmth, patient-reported joint swelling, time from pain onset to peak, and self-reported acute CPP crystal inflammatory arthritis were included in the multivariable logistic model. This model had good discrimination (optimism-adjusted c-index: 0.92; 95% CI: 0.89, 0.95) and calibration (optimism-adjusted calibration slope: 0.95; 95% CI: 0.71, 1.19; optimism-adjusted calibration-in-the-large: 0.005; 95% CI: −0.37, 0.37) in the internal validation. Probability threshold ≥0.53 had sensitivity of 0.83 (95% CI: 0.74, 0.90) and specificity of 0.86 (95% CI: 0.79, 0.91). Performances were similar in the internal–external cross-validation. The CART identified patient-reported acute CPP crystal inflammatory arthritis, followed by joint swelling and joint warmth as the most informative variables for ascertaining acute CPP crystal arthritis [sensitivity 0.83 (95% CI: 0.72, 0.91) and specificity 0.83 (95% CI: 0.74, 0.90)].<div class="boxTitle">Conclusion</div>We developed and initially validated easy-to-use patient-reported definitions for acute CPP crystal arthritis for use in clinical trials and observational research in CPPD.</span>
<span class="paragraphSection"><span style="text-transform:lowercase;font-variant:small-caps;">Dear Editor</span>, We read with interest the recent article by Snoeck Henkemans <span style="font-style:italic;">et al.</span> [<a href="#keae685-B1" class="reflinks">1</a>]. They aimed to investigate whether the presence of depression or anxiety could affect failure to achieve remission and components of disease activity in patients with RA and PsA. Administration of the Hospital Anxiety and Depression Scale at multiple time points during follow-up allowed assessment of the temporal changes between depression, anxiety and remission over time. They concluded that both depression and anxiety are associated with a lower likelihood of remission in both patient groups. Also, they reported that the presence of depression or anxiety was associated with more tender joints, worse general health and more pain [<a href="#keae685-B1" class="reflinks">1</a>].</span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Objectives</div>To evaluate the impact of thyroid diseases (TDs) on the comorbidities incidence and immune system of patients with primary SS (pSS).<div class="boxTitle">Methods</div>A total of 329 patients diagnosed with pSS who were admitted between January 2018 and September 2023 were evaluated. The patients were divided into two groups: those with and without TD. Clinical data at the onset of SS were recorded. Kaplan–Meier method and Cox proportional hazards model were utilized for survival analysis. Flow cytometry and immunofluorescence measurements were used to analyse the lymphocyte subtypes.<div class="boxTitle">Results</div>Of the 329 patients, 109 had TD. The most common types of TD were thyroid nodules (40.4%) and autoimmune thyroid diseases (AITDs) (28.4%). Patients with TD exhibited a significantly elevated incidence risk of malignancy (14.7% vs. 6.4%, <span style="font-style:italic;">P</span> = 0.01) and osteoporosis (OP) (23.9% vs. 14.1%, <span style="font-style:italic;">P</span> = 0.03). TD comorbidity was an independent risk factor of malignancy (HR 4.7, 95% CI 1.1–19.3, <span style="font-style:italic;">P</span> = 0.03) and OP (HR 3.7, 95% CI 1.3–10.2, <span style="font-style:italic;">P</span> = 0.01). Patients with SS and TD exhibited a higher ratio of programmed death-1 (PD1) + subsets of total CD3+ T cells, Th and Tc cells (all <span style="font-style:italic;">P</span> = 0.03), as well as a lower ratio of unswitched memory B cells (<span style="font-style:italic;">P</span> = 0.01) in peripheral blood. The ratio of PD1+ subsets of Th cells in salivary glands also exhibited a significantly increase in these patients compared with those without TD (<span style="font-style:italic;">P</span> = 0.03) and the controls (<span style="font-style:italic;">P</span> < 0.01).<div class="boxTitle">Conclusion</div>The incidence risk of malignancy and OP was significantly elevated in pSS patients with TD. The significant elevated proportions of PD1+ T cells may influence the occurrence of this process.</span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Objectives</div>To evaluate the combination of novel colour Doppler US (CDUS), greyscale US (GSUS), and oscillometric indices of macroangiopathy in patients with idiopathic inflammatory myopathies (IIM). Second, to explore the associations between these imaging markers and both patient-related and disease-related characteristics, as well as traditional cardiovascular (CV) risk factors.<div class="boxTitle">Methods</div>We conducted CDUS to evaluate arterial compliance markers, specifically the resistance (RI) and pulsatility (PI) indices, both in the common (CCA) and internal carotid arteries (ICA) of patients with IIM and healthy controls. Additionally, we performed GSUS examinations to measure carotid intima-media thickness (cIMT), identify plaques, and quantify cumulative carotid calcification surface. Oscillometric assessments determined aortic stiffness using carotid-femoral pulse wave velocity (cfPWV).<div class="boxTitle">Results</div>We recruited 82 IIM patients and 88 healthy controls. Patients showed significantly higher cIMT (<span style="font-style:italic;">P</span><sub>adj</sub> = 0.032), CCA-RI (<span style="font-style:italic;">P</span><sub>adj</sub> = 0.015), CCA-PI (<span style="font-style:italic;">P</span><sub>adj</sub> = 0.013), ICA-RI (<span style="font-style:italic;">P</span><sub>adj</sub> = 0.012), and ICA-PI (<span style="font-style:italic;">P</span><sub>adj</sub> = 0.039), compared with controls. RI and PI of CCA and ICA were higher in patients with lower lung function vital capacity, respectively (all <span style="font-style:italic;">P</span>s < 0.05). cfPWV correlated positively with traditional CV risk factors including age (ρ = 0.546, <span style="font-style:italic;">P</span> < 0.001), mean arterial pressure (ρ = 0.331, <span style="font-style:italic;">P</span> = 0.003), diabetes (<span style="font-style:italic;">P</span> = 0.007), and hyperlipidaemia (<span style="font-style:italic;">P</span> = 0.032), and associated negatively with lung carbon monoxide (CO) diffusion (ρ = −0.329, <span style="font-style:italic;">P</span> = 0.031).<div class="boxTitle">Conclusion</div>In one of the largest CV surrogate marker studies in IIM, patients exhibited increased carotid pulsatility, resistance, and atherosclerosis compared with controls. Lower lung function parameters predicted aortic stiffness and Doppler indices, suggesting a possible link between lung involvement and increased CV risk. Angiopathy markers may reveal significant vascular abnormalities in IIM patients, enhancing CV screening and risk classification.</span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Objectives</div>The efficacy of avacopan as remission induction therapy for Anti-Neutrophil Cytoplasmic Autoantibody (ANCA)-associated vasculitis (AAV) is well-established. However, concerns regarding liver injury post-avacopan treatment remain, especially in Japan. Therefore, this study aimed to investigate drug-induced liver injury (DILI) associated with avacopan treatment.<div class="boxTitle">Methods</div>This study included 22 patients with AAV who were treated with avacopan at multiple centres in Japan between September 2021 and March 2024. DILI was assessed by the Japanese version of a revised electronic causality assessment method (RECAM-J 2023).<div class="boxTitle">Results</div>Among the 22 patients treated with avacopan, DILI was observed in nine cases (40.9%): six with microscopic polyangiitis and three with granulomatosis with polyangiitis. Severe DILI with elevated total bilirubin (T-Bil) was observed in four of the nine patients (44.4%), a few weeks after the initiation of avacopan therapy. Eight of the nine patients (88.9%) with DILI improved after discontinuation of avacopan and other medications, and one patient developed vanishing bile duct syndrome (VBDS) leading to death. Avacopan-induced DILI was classified into three patterns: 1, short-term injury without T-Bil elevation; 2, transient cholestatic liver injury with T-Bil elevation; 3, decompensated liver injury with marked T-Bil elevation (VBDS). The risk factors for severe DILI with T-Bil elevation in Japanese patients included older age, lower body mass index and early onset DILI following the initiation of avacopan treatment.<div class="boxTitle">Conclusion</div>Avacopan-induced DILI is relatively common in Japan and could be lethal. Frequent laboratory follow-ups should be considered, especially for elderly and low-body-weight patients.</span>
<span class="paragraphSection"><span style="text-transform:lowercase;font-variant:small-caps;">Dear Editor</span>, We appreciate the interest in our article by Kaya <span style="font-style:italic;">et al.</span> [<a href="#keae686-B1" class="reflinks">1</a>, <a href="#keae686-B2" class="reflinks">2</a>] and would like to respond to their Letter to the Editor. Kaya <span style="font-style:italic;">et al.</span> argue that patients with RA and PsA may experience nociceptive, neuropathic, nociplastic or mixed pain. Therefore, pain should not only be measured with a visual analogue scale capturing nociceptive pain but with a questionnaire that can differentiate between the different types of pain [<a href="#keae686-B3" class="reflinks">3</a>].</span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Objectives</div>Ultrasonographic assessment of giant cell arteritis (GCA) relies on the demonstration of a non-compressible halo. Several ultrasonographic methods have been developed to quantify arterial wall thickness; however, arterial compressibility has not been quantified. This study presents a possible solution for quantifying compressibility to assist in diagnosing GCA.<div class="boxTitle">Methods</div>Cross-sectional areas of uncompressed and compressed arteries were measured ultrasonographically, and their ratio was calculated [compression ratio (CR)]. The values obtained were tested for a relationship with the diagnosis of GCA and diagnostic performance was compared against halo count (HC).<div class="boxTitle">Results</div>Ultrasound findings from 304 patients (65.8% females) were divided into GCA arm (<span style="font-style:italic;">n</span> = 72) and Not-GCA arm (<span style="font-style:italic;">n</span> = 232). The CR values for patients in the GCA arm were significantly lower than the Not-GCA arm whether compared as the individual patient mean or lowest CR value (Mann–Whitney <span style="font-style:italic;">U</span> test <span style="font-style:italic;">P</span> <0.001). The CR values observed in this study from a single skilled clinician suggest a threshold CR value of ≤2.3 for predicting a diagnosis of GCA. If confirmed in other studies this would effectively provide a quantitative measure that might help training sonographers confirm a visually identified halo sign and enhance objectivity in ultrasonographic assessment of GCA.<div class="boxTitle">Conclusion</div>Compression ratio (CR) is a novel quantifiable measure that contributes to the ultrasound assessment of GCA. It is worthy of further research and in clinical application, it is a measurement that may enhance diagnostic certainty.</span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Objective</div>Calcium pyrophosphate deposition (CPPD) disease is associated with an increased risk for cardiovascular (CV) events. We examined the atherosclerotic burden by coronary artery calcium (CAC) scores (Agatston score) and compared 10-year atherosclerotic CV disease (ASCVD) risk scores in patients with vs without chondrocalcinosis, a radiographic marker of CPPD.<div class="boxTitle">Methods</div>We performed a cross-sectional analysis at an academic medical centre, 1991–2022. Among all patients with an Agatston score in routine care, we defined a cohort with chondrocalcinosis detected before the CAC scan. Comparators without chondrocalcinosis were matched 2:1 on age and sex—the primary analysis excluded statin users. We compared Agatston scores between the chondrocalcinosis cohort and comparators. We also tested for differences between cohorts in 10-year ASCVD risk score frequencies (low, borderline/intermediate or high).<div class="boxTitle">Results</div>756 patients with chondrocalcinosis were matched to 1554 comparators (mean age 68 years, 53% female). CV risk factor burden was high in both cohorts, and statin use was infrequent. The unadjusted Agatston score was non-significantly higher in the chondrocalcinosis cohort (mean 359.1, <span style="text-transform:lowercase;font-variant:small-caps;">s</span>.<span style="text-transform:lowercase;font-variant:small-caps;">d</span>. 737.9) than in matched comparators (mean 297.1, <span style="text-transform:lowercase;font-variant:small-caps;">s</span>.<span style="text-transform:lowercase;font-variant:small-caps;">d</span>. 644.9) (<span style="font-style:italic;">P</span> = 0.08). High 10-year ASCVD risk scores were significantly more common in the chondrocalcinosis cohort than comparators (<span style="font-style:italic;">P</span> < 0.01).<div class="boxTitle">Conclusion</div>Coronary atherosclerosis burden by CAC was not significantly different between patients with chondrocalcinosis and matched comparators, though 10-year ASCVD risk scores were higher in the chondrocalcinosis cohort, suggesting that factors beyond coronary artery calcification contribute to the increased CV event rate in patients with CPPD disease.</span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Objectives</div>To determine the clinical outcomes of patients with immunoglobulin 4-related disease (IgG4-RD) treated with a defined B-cell depletion protocol using rituximab.<div class="boxTitle">Methods</div>Patients were included if they had (i) an IgG4-RD diagnosis at Imperial College Healthcare NHS Trust between February 2017 and October 2022, and (ii) >9 months of follow-up data available following the first rituximab dose. The rituximab protocol targeted B-cell depletion to <10 cells/microliter for a maintenance period of two years. Electronic records were used to define patient demographics, serological and radiological variables and treatment responses according to the IgG4-RD responder index (RI).<div class="boxTitle">Results</div>Forty-five patients received induction treatment with rituximab. Two patients had insufficient follow-up data for outcome analysis. All patients responded to rituximab therapy according to the IgG4-RD RI. Most patients (25/43, 58%) were also treated with low-dose glucocorticoids at the time of rituximab induction (median prednisolone dose 5 mg daily) and 4/25 (16%) remained on prednisolone at two years (median prednisolone dose 5 mg daily). Disease flares occurred in 11/43 (26%) patients; 9/11 flares occurred in the presence of B-cell repopulation; 2/11 (18.1%) flares occurred in the absence of B-cell repopulation (>10 cells/uL). All flares re-treated with rituximab (7/7, 100%) responded positively.<div class="boxTitle">Conclusion</div>Rituximab administration targeting B-cell depletion for a two-year period is an effective treatment strategy for IgG4-RD and can limit the cumulative glucocorticoid exposure. Flares are uncommon and typically occur in the setting of B-cell repopulation, with good clinical responses to further rituximab administration.</span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Objectives</div>Cutaneous vasculitis (CV) is common in SLE, but the epidemiology and risk factors remain unclear. We aimed to identify the trends and risk factors for CV in patients with SLE over a period of 20 years.<div class="boxTitle">Methods</div>The Birmingham Lupus Cohort is an observational longitudinal cohort of SLE patients. Patients were enrolled within 3 years of meeting their fourth ACR criterion. Disease activity, laboratory test results and treatment records were collected. A multivariable shared frailty Cox proportional hazard model was used to identify clinical, laboratory and treatment-related variables associated with the development of CV.<div class="boxTitle">Results</div>We included 392 patients: 95.7% were female. The median (interquartile range) duration of follow-up was 9.2 (5.1–14.7) years. CV occurred in 27% of SLE patients, of whom 43.3% had two or more CV events. This study demonstrated a marked decline in the incidence rates of CV, decreasing from 34.4% (95% CI 29.7, 39.3) during the first 3 years after enrolment to 2.1% (95% CI 0.05, 11.5) after 18 years of follow-up. Development of CV was associated with RP, constitutional, mucocutaneous, musculoskeletal, haematological and cardiovascular involvement, anti-Sm antibodies, anti-dsDNA, and hypocomplementemia. However, the use of AZA and antimalarials was inversely associated with the development of CV. Patients with CV were more likely to develop at least one item of organ damage.<div class="boxTitle">Conclusions</div>The incidence rates of CV in SLE decreased over the follow-up period and CV is associated with defined clinical, serological and treatment-related factors.</span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Objective</div>The spectrum of GCA includes various vascular phenotypes. Tocilizumab (TCZ) is the only biologic therapy currently approved, regardless of phenotype. We aimed to assess the effectiveness of TCZ in various phenotypes.<div class="boxTitle">Methods</div>This is a multicentre observational study of GCA patients treated with TCZ. They were divided into three phenotypes: (i<strong>)</strong> cranial (cGCA), (ii<strong>)</strong> extracranial GCA (ecGCA) and (iii<strong>)</strong> mixed GCA (mixGCA). Outcomes included clinical remission, EULAR complete remission, relapses, absence of inflammation as shown using imaging techniques, and safety.<div class="boxTitle">Results</div>We studied 471 patients (342 women; mean age 74.0 ± 9.0 years). The phenotypic distribution was: cGCA (<span style="font-style:italic;">n</span> = 217; 46%), mixGCA (174; 37%) and ecGCA (80; 17%). Patients with ecGCA were younger (66.5 ± 10.1 years) than those with cGCA (74.8 ± 8.1) and those with mixGCA (71.4 ± 8.5), and had a longer delayed GCA diagnosis {median [interquartile range (IQR) [6 (1–14)] <span style="font-style:italic;">vs</span> 1 (1–3) <span style="font-style:italic;">vs</span> 2 (1–6) months, respectively}. Systemic manifestations were similar in the three groups, while ischaemic manifestations were more frequent in cGCA. Combined TCZ, in addition to glucocorticoids, was used more frequently in ecGCA (36%). Clinical remission was observed in 51%/43%/47% in cGCA/ecGCA/mixGCA, respectively, after the first month, and in 79%/81%/89% after 24 months. Complete EULAR remission in 35%/27%/28% (after 1 month) and 72%/73%/67% (after 24 months). Absence of inflammation being shown in the imaging techniques was 15%/26% after 12 months, and 22%/7% (ecGCA/mixGCA) (after 24 months). Relevant adverse events were observed in 109 (23.1%) patients.<div class="boxTitle">Conclusion</div>TCZ shows rapid and maintained effectiveness in all GCA phenotypes in clinical remission and EULAR complete remission. By contrast, absence of inflammation as shown using imaging techniques was much lower in ecGCA and mixGCA.</span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Objective</div>Among adults who develop coronavirus disease 2019 (COVID-19), those with rheumatic diseases (RDs) have similar hospitalization rates compared with those without RDs. Similar comparisons are lacking in children, due to the overall rarity of COVID-19-related hospitalization in this population. We aimed to examine the risk factors for COVID-19-related hospitalization in paediatric patients with RDs.<div class="boxTitle">Methods</div>We conducted a systemic literature search in MEDLINE, EMBASE, Web of Science and China National Knowledge Infrastructure from 1 December 2019, through 22 January 2024. We included observational studies based on inclusion and exclusion criteria. Odds ratios (ORs) with 95% CI were calculated.<div class="boxTitle">Results</div>Eight cohort studies capturing 1501 paediatric RD patients with SARS-CoV-2 and 118 COVID-19-related hospitalization were included. Odds of hospitalization was increased in children with RDs compared with healthy children. While the diagnosis of juvenile idiopathic arthritis (JIA) was associated with reduced odds of hospitalization overall (OR 0.43 [95% CI: 0.27, 0.68]), systemic JIA was associated with increased odds of hospitalization (OR 2.54 [95% CI: 1.01, 6.40]). The use of glucocorticoids (OR 5.36 [95% CI: 2.21, 13.04]), rituximab (OR 4.62 [95% CI: 1.87, 11.40]), mycophenolate mofetil (OR 4.17 [95% CI: 1.08, 16.16]), hydroxychloroquine (OR 2.97 [95% CI: 1.42, 6.21]), and IL-1 inhibitors (OR 2.28 [95% CI: 1.09, 4.78]) was associated with increased odds of hospitalization, while the use of TNFα inhibitors was associated with reduced odds (OR 0.35 [95% CI: 0.20, 0.66]).<div class="boxTitle">Conclusion</div>Children with RDs are at risk of severe COVID-19 outcomes, while children with JIA taking TNFα inhibitors might be at a lower risk.</span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Objective</div>SSc is disabling. However, the different factors contributing to this disability and how these change over time have been little studied. Our aim was to examine the trajectories over time of the six visual analogue scales (VAS) of the Scleroderma HAQ (SHAQ), associations of disease-related factors with these trajectories, and relationships with overall functional ability.<div class="boxTitle">Methods</div>This was a retrospective study of data collected prospectively from patients attending a single tertiary centre between 2005 and 2022. VAS (pain, intestinal, breathing, RP, digital ulcers, ‘overall’) were analysed using linear mixed-effects models, and relationships between the six VAS and functional ability [HAQ Disability Index (HAQ-DI)] and scleroderma functional index (FI) by correlating the average gradients obtained from individual linear regressions.<div class="boxTitle">Results</div>A total of 537 patients with at least two time-points were included, followed for a mean (<span style="text-transform:lowercase;font-variant:small-caps;">s</span>.<span style="text-transform:lowercase;font-variant:small-caps;">d</span>.) of 6.8 (4.2) years. VAS intestinal scores increased (i.e. worsened) by 0.085 points (95% CI 0.041–0.130, <span style="font-style:italic;">P</span> < 0.001) per year, VAS breathing by 0.056 points (95% CI 0.016–0.096, <span style="font-style:italic;">P</span> = 0.006) and VAS overall scores by 0.073 points (95% CI 0.032–0.114, <span style="font-style:italic;">P</span> = 0.001). The longer the duration between RP onset and SSc diagnosis, the lower the VAS pain and VAS intestinal scores. The odds of having at least one digital ulcer reduced with disease duration, with diffuse cutaneous subtype and with anti-Scl70 positivity. Average gradients for all six VAS scales correlated (albeit variably/weakly) with HAQ-DI and scleroderma FI gradients.<div class="boxTitle">Conclusion</div>Longitudinal assessment of the six SHAQ VAS, and associations of baseline characteristics with the individual VAS time courses, provide insights into disease trajectory and overall disability.</span>
<span class="paragraphSection"><div class="boxedTextSection">Rheumatology key message<ul><li class="bullet">For RA patients presenting with complex pericardial effusions, tuberculosis should be considered as an important differential, with challenges surrounding diagnosis and management making multidisciplinary input essential.</li></ul></div></span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Objectives</div>To evaluate the experiences of patients with spondyloarthritis (SpA) and their healthcare providers (HCPs) with patient-initiated follow-up (PIFU) supported by asynchronous telemedicine (TM) compared with their past experiences with usual care, and to identify prerequisites for sustainable implementation of PIFU/TM.<div class="boxTitle">Methods</div>Individual, semi-structured interviews were conducted with purposefully selected patients (<span style="font-style:italic;">n</span> = 21) and HCPs (<span style="font-style:italic;">n</span> = 9) who previously participated in the ‘TeleSpA’ randomised controlled trial and thematically analysed. PIFU/TM consisted of a once-yearly pre-planned physical visit with in-between remote monitoring at 6 months. Additionally, 13 HCPs completed a quantitative survey, which was analysed descriptively.<div class="boxTitle">Results</div>Most patients and HCPs found PIFU/TM acceptable, given the presence of sufficient health literacy, digital literacy and motivation. Most patients felt no burdensome changes to their personal responsibility, and both in-person and remote communication between stakeholders ran smoothly. Advantages for patients included time savings, and improvements in disease insight and self-efficacy. Some HCPs experienced increased flexibility in their daily planning. Pivotal prerequisites for sustainable implementation were adequate infrastructure to conduct ad hoc diagnostic tests, assured rapid access to the outpatient clinic when necessary, availability of technical and logistical support, and a user-friendly monitoring tool integrated with existing hospital information systems. Fine-tuning the design and delivery of questionnaires as part of TM is an opportunity for future research.<div class="boxTitle">Conclusion</div>PIFU/TM was perceived as an acceptable approach for the follow-up of motivated patients with SpA with adequate health literacy and digital literacy. Preserved accessibility to the outpatient clinic and availability of ancillary support are essential for its sustainable implementation.</span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Objective</div>In axSpA, validated PROs are well-established in clinical trials, but it remains unclear whether they comprehensively reflect patients’ discomfort and disease status. We aimed to investigate how patients’ self-reported disease status compares with validated clinical trial measures during routine clinical visits.<div class="boxTitle">Methods</div>Data from axSpA patients’ initial and last five visits were retrospectively analysed. ASDAS, BASDAI, ASAS20, ASAS40 and ASAS partial remission were assessed at each visit and compared with patients’ self-reported disease status, categorized into very good (status satisfaction), mild, severe and very severe based on patients’ self-reported opinion on the level of severity of symptom burden related to axSpA. The association of these PROs with patients’ self-reported disease status was analysed using mixed models.<div class="boxTitle">Results</div>A total of 3,120 visits over a median follow-up of 4.7 years from 557 axSpA patients were analyzed. Very good or mild self-reported disease status was reported in 98.7% of visits with inactive and 90.9% of visits with low ASDAS compared to 67.9% with high and 39.3% with very high ASDAS. Severe or very severe self-reported disease status was reported in 15.1% of visits with ASAS20 achievement, in 7.2% with ASAS40 achievement, and in 0.6% with achievement of ASAS partial remission, compared with 26.0% without ASAS20 achievement, 25.1% without ASAS40 achievement, and 30.1% without achievement of ASAS partial remission.<div class="boxTitle">Conclusions</div>Patients’ self-reported disease status was well captured by ASDAS and BASDAI in most clinical visits. Other investigated measures used in clinical trials failed to capture patients’ self-reported disease status in a large proportion of visits.</span>
<span class="paragraphSection"><span style="text-transform:lowercase;font-variant:small-caps;">Dear Editor</span>, It is with great interest that we read the recently published article entitled ‘The 2024 British Society for Rheumatology guideline for management of systemic sclerosis’ by Denton <span style="font-style:italic;">et al</span>. [<a href="#keae657-B1" class="reflinks">1</a>]. Although the article comprehensively describes the medical treatment options for the management of SSc, it only briefly attends to the non-pharmacological SSc treatments, in general, and to exercise in specific. As the latter has demonstrated several benefits in this population, we are writing this short critique to draw your readers’ attention to those.</span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Objectives</div>This study aimed to address the lack of gene expression regulation data in synovial tissues and to identify genes associated with rheumatoid arthritis (RA) in the synovium, a primary target tissue for RA.<div class="boxTitle">Methods</div>Gene expression prediction models were built for synovial tissue using matched genotype and gene expression data from 202 subjects. Using this model, we conducted a transcriptome-wide association study (TWAS), utilizing the largest rheumatoid arthritis (RA) genome-wide association study (GWAS) meta-analysis data (<span style="font-style:italic;">n</span> = 276 020). Further analyses, including conditional and joint analysis, causal analysis, differential expression analysis and gene-set enrichment analysis, were conducted to deepen our understanding of genetic architecture and comorbidity aetiology of RA.<div class="boxTitle">Results</div>Our analysis identified eight genes associated with rheumatoid arthritis (RA), including three novel genes: <span style="font-style:italic;">TPRA1</span> (<span style="font-style:italic;">P</span><sub>TWAS</sub> = 9.59 × 10<sup>−6</sup>), <span style="font-style:italic;">HIP1</span> (<span style="font-style:italic;">P</span><sub>TWAS</sub> = 1.47 × 10<sup>−5</sup>) and <span style="font-style:italic;">RP11-73E17.2</span> (<span style="font-style:italic;">P</span><sub>TWAS</sub> = 3.32 × 10<sup>−7</sup>). These genes differed from those identified in previous TWAS studies using alternative tissues and may play a crucial role in the target synovial tissue. We found four genes exhibited significant causal relationships with RA and were differentially expressed in RA patients. Furthermore, we explored potential drug repurposing opportunities for these genes.<div class="boxTitle">Conclusions</div>Our study is the first to model gene expression in synovial tissue, uncovering novel genetic determinants of rheumatoid arthritis (RA). This advancement not only deepens our understanding of RA's genetic architecture, but also offers promising avenues for targeted therapies and drug repurposing.</span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Objective</div>High disease activity status (HDAS) in patients with systemic lupus erythematosus (SLE) is associated with adverse long-term outcomes. We examined the frequency of lupus low disease activity state (LLDAS) and remission (REM) attainment in HDAS patients and whether their attainment was associated with improved patient outcomes.<div class="boxTitle">Methods</div>Demographic, clinical and outcomes data, collected prospectively from a multinational cohort between 2013 and 2020, were analysed. Disease activity was assessed using SLEDAI-2K. HDAS was defined as SLEDAI-2K ≥ 10. Patients’ first visit with SLEDAI-2K ≥ 10 was assigned as baseline. Survival analyses were performed to examine the associations between cumulative and sustained LLDAS and REM attainment in HDAS patients and subsequent organ damage accrual and flare.<div class="boxTitle">Results</div>A total of 1029 HDAS patients with a median study duration of 2.7 years [IQR: 1.0, 4.8] were studied. LLDAS and REM were attained at least once by 71% (LLDAS-ever, <span style="font-style:italic;">n</span> = 726) and 41% (REM-ever, <span style="font-style:italic;">n</span> = 418) of patients. Approximately one-fifth of patients attained ≥50% cumulative time in LLDAS or REM. In total, 37% (<span style="font-style:italic;">n</span> = 385) of patients attained ≥3months of sustained LLDAS, with progressively lower proportions of patients attaining longer periods of sustained LLDAS. Lower proportions of patients attained sustained REM. Attainment of cumulative and sustained LLDAS or REM provided significant protection against damage accrual and flare in HDAS patients. Sustained periods of LLDAS and REM were difficult to achieve and were therefore a more stringent target, but provided the most protection against damage accrual or flare.<div class="boxTitle">Conclusion</div>LLDAS and REM were achievable targets in HDAS patients, and provided significant protection against adverse outcomes.</span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Objective</div>Childhood SjD (cSjD) is a rare disease. There are no widely accepted diagnostic or classification criteria for cSjD. To fill this gap, members from the CARRA Sjögren Disease Workgroup and the International Childhood Sjögren Disease Workgroup created a clinical diagnostic algorithm. This study evaluated the accuracy of this algorithm using an international cohort of participants with clinician-diagnosed cSjD.<div class="boxTitle">Methods</div>First, experts developed a cSjD diagnostic algorithm through a series of virtual workgroup meetings. Using the adult classification criteria as a framework, experts modified the algorithm through opinion and literature review. The group discussed and finalized each algorithm step by achieving majority rule. Then, R statistical software was used to evaluate each participant’s disease status in the diagnostic algorithm via an international cohort of 300 cSjD cases.<div class="boxTitle">Results</div>The diagnostic algorithm has three distinct clinical pathways representing the key clinical presentation in cSjD: parotitis, extraglandular manifestations, and sicca symptoms. The algorithm showed an overall sensitivity of 75% in the population that had enough data to complete at least one pathway of the algorithm (<span style="font-style:italic;">n</span> = 100 filtered out of 300). The parotitis (70%) and sicca pathways (82%) had the highest sensitivity, and the extraglandular pathway (52%) had the lowest.<div class="boxTitle">Conclusion</div>As cSjD lacks a diagnostic strategy, this algorithm provides a clinical tool for evaluating children with cSjD-like symptoms. It performed well in an international cohort of cSjD, supporting the integration of this algorithm into clinical practice; however, its utility may be limited by low utilization of diagnostic testing in this population.</span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Objective</div>Evaluate the efficacy and safety of guselkumab, an IL-23p19-subunit inhibitor, in a phase 2, multicentre, randomized, double-blind, placebo-controlled study of patients with active LN.<div class="boxTitle">Methods</div>Adults (18–75 years) with active LN [Class III–IV proliferative nephritis (kidney biopsy) and urine protein-to-creatinine ratio (UPCR) of ≥1 mg/mg despite standard-of-care therapy] were randomized (1:1; planned sample = 60) to receive i.v. infusions of guselkumab 400 mg or placebo at weeks 0, 4 and 8, then s.c. injections (guselkumab 200 mg or placebo) at week 12 and every 4 weeks through week 48 in addition to their background therapy. The primary endpoint was achievement of ≥50% decrease in proteinuria from baseline at week 24. Major secondary endpoints (week 24) were achievement of complete renal response (CRR), sustained reduction in steroid dose (≤10 mg/day prednisone/equivalent) from weeks 16–24, UPCR <0.5 mg/mg; <0.75 mg/mg, time to achieving CRR, and time to treatment failure. Safety was assessed through the end of the study.<div class="boxTitle">Results</div>Following enrolment challenges (COVID-19 pandemic; Ukraine/Russia crisis), the sponsor terminated the study early; 33 participants were randomized (placebo, <span style="font-style:italic;">n</span> = 16; guselkumab, <span style="font-style:italic;">n</span> = 17). At week 24, 56.3% (9/16) in the placebo group and 35.3% (6/17) in the guselkumab group achieved the primary endpoint. No apparent differences were observed in the secondary endpoints. Through end-of-study, 75% of placebo patients and 71% of guselkumab patients reported ≥1 adverse event; most were of mild-to-moderate severity.<div class="boxTitle">Conclusion</div>Guselkumab+background therapy did not demonstrate superior reduction in proteinuria <span style="font-style:italic;">vs</span> placebo+background therapy in this small cohort of patients with active LN. Safety results were consistent with the known safety profile of guselkumab.<div class="boxTitle">Trial registration</div><a href="http://www.ClinicalTrials.gov">ClinicalTrials.gov</a>: NCT04376827.</span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Objective</div>To evaluate the long-term effectiveness of the combination of Iguratimod (IGU) and Alendronate for patients with Synovitis, Acne, Pustulosis, Hyperostosis and Osteitis (SAPHO) syndrome.<div class="boxTitle">Methods</div>A prospective cohort study was conducted on patients diagnosed with SAPHO syndrome at Peking University Third Hospital and Beijing Jishuitan Hospital from 2017 to 2024. The initial treatment regimen comprised a combination of IGU and Alendronate. Patients who were followed up for >2 years were included in our study. We collected demographic data, clinical symptoms, recurrence rates, treatment duration and overall response to therapy for all patients.<div class="boxTitle">Results</div>Seventeen patients were recruited for our cohort, with a median (IQR) follow-up of 2.91 (2.34) years. The mean treatment duration was 39.10 months. Among patients with osteoarticular involvement (17/17), 35.30% (6/17) achieved complete improvement without any recurrence, 11.76% (2/17) showed partial improvement and 52.94% (9/17) experienced intermittent flares. For patients with skin involvement (11/17), 63.64% (7/11) achieved complete improvement, 27.27% (3/11) had partial improvement and 9.09% (1/11) experienced intermittent recurrence. Notably, 88.26% (15/17) regained complete independence and resumed work, and 94.12% (16/17) experienced alleviation of anxiety and insomnia. By the end of last follow-up, 52.94% (9/17) had ceased treatment after a mean duration of 25.22 months and 22.22% (2/9) of them encountered recurrence.<div class="boxTitle">Conclusion</div>The combination of IGU and Alendronate as initial treatment may be effective for the long-term management of SAPHO syndrome. ∼41% of the patients could discontinue treatment after more than two years without recurrence.</span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Objectives</div>The objectives of this study were to evaluate the frequency and timing of sustained drug-free remission (SDFR) in patients with GCA and to identify potential predictive factors of this outcome.<div class="boxTitle">Methods</div>A retrospective review of all patients included in the large Spanish multicentre registry for GCA (ARTESER) with at least 2 years of follow-up was undertaken. SDFR was defined as the absence of typical signs, symptoms, or other features of active GCA for ≥12 months after discontinuation of treatment.<div class="boxTitle">Results</div>We included 872 patients. Forty-seven percent had received concomitant treatment with tocilizumab and/or immunosuppressants, mainly MTX. SDFR was achieved in 21.2% (185/872) of the patients. The cumulative rates of patients achieving SDFR at 2, 3 and 4 years were 6.3%, 20.5% and 25.3%, respectively. Patients who achieved SDFR could reduce their prednisone dosage to 10 mg/day (<span style="font-style:italic;">P</span> = 0.090) and 5 mg/day (<span style="font-style:italic;">P</span> = 0.002) more quickly than those who did not. Relapses were less frequent in patients with SDFR (<span style="font-style:italic;">P</span> = 0.006). The presence of relapses [incident rate ratio (IRR): 0.492, <span style="font-style:italic;">P</span> < 0.001] and the need for i.v. methylprednisolone boluses at diagnosis (IRR: 0.575, <span style="font-style:italic;">P</span> = 0.003) were significantly associated with a decreased likelihood of achieving SDFR. Only 5 patients (2.7%) experienced a recurrence, with a median onset of 19 months after achieving SDFR (interquartile range 25th–75th: 14–35 months).<div class="boxTitle">Conclusion</div>Within 3–4 years of diagnosis, only one-quarter of patients with GCA successfully reached the SDFR. Once the SDFR was achieved, the likelihood of experiencing recurrence was low. Relapses and the need for glucocorticoid boluses appear to have been predictors of the need for long-term glucocorticoids.</span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Objectives</div>To investigate factors associated with DM complete clinical response and overall survival with a focus on the use of immunosuppressive therapies in patients with cancer-associated DM.<div class="boxTitle">Methods</div>We performed a multicentre, retrospective cohort study. Multivariable survival analyses used a Cox model with time-dependent covariates and adjustments with inverse probability censoring weighting.<div class="boxTitle">Results</div>We included 73 patients with cancer-associated DM. Median follow-up was 3.92 years. Overall, 40 (54.8%) patients achieved cancer remission, with DM complete clinical response in 28/40 (70.0%). DM complete clinical response was associated with cancer remission (hazard ratio [HR] 2.46, 95% CI [1.13–5.32]) and younger age (HR 0.68, 95% CI [0.49–0.95]). Risk of mortality was associated with sustained cancer activity (HR 12.93, 95% CI [2.42–69.25]), male sex (HR 2.82, 95% CI [1.19–6.70]), and older age (HR 1.86, 95% CI [1.26–2.79]) but not sustained DM activity (HR 0.40, 95% CI [0.13–1.26]). Oral corticosteroid use was a protective factor only on univariate analysis (HR 0.18, 95% CI [0.08–0.42]). <div class="boxTitle">Conclusion</div>This study provides strong evidence of a significant association between the evolutions of DM and cancer, both in terms of overall survival and DM complete clinical response. Immunosuppressive treatments for DM were not significantly associated with mortality. <div class="boxTitle">Trial registration</div>ClinicalTrials.gov, NCT04637672.</span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Objectives</div>As fibroblast-like synoviocyte activation and bone formation are associated with PsA, PET using the tracers of <sup>68</sup>Ga-fibroblast activation protein inhibitor (FAPI) and <sup>18</sup>F-sodium fluoride (NaF) may sensitively detect the disease. In this prospective study, we aimed to evaluate the performance of <sup>68</sup>Ga-FAPI PET/CT in PsA and to compare it with <sup>18</sup>F-NaF PET/CT.<div class="boxTitle">Methods</div>Sixteen participants (female 7/16, age 42.31 ± 10.66 years) with PsA were prospectively enrolled and underwent dual-tracer PET/CT, clinical assessment and ultrasonography. PET/CT images were scored for PET-positive lesions at the peripheral joints, entheses, and axial joints.<div class="boxTitle">Results</div>The positivity rate of <sup>68</sup>Ga-FAPI in peripheral joints was higher than that in entheses and axial joints (21.84% <span style="font-style:italic;">vs</span> 12.15% <span style="font-style:italic;">vs</span> 0%), whereas high positivity rates of <sup>18</sup>F-NaF in peripheral joints, entheses, and axial joints were observed (85.23%, 78.13% and 75%, respectively). The DAS 28 was higher in the PET-positive than in the PET-negative group with <sup>68</sup>Ga-FAPI (5.25 ± 1.84 <span style="font-style:italic;">vs</span> 2.55 ± 0.94, <span style="font-style:italic;">P</span> = 0.037), but not with <sup>18</sup>F-NaF. In addition, the PET joint count at <sup>68</sup>Ga-FAPI PET/CT was positively correlated with the tender joint count (<span style="font-style:italic;">r</span> = 0.604, <span style="font-style:italic;">P</span> = 0.017), swollen joint count (<span style="font-style:italic;">r</span> = 0.773, <span style="font-style:italic;">P</span> = 0.001), DAS28-CRP (<span style="font-style:italic;">r</span> = 0.556, <span style="font-style:italic;">P</span> = 0.032), Psoriatic Arthritis Disease Activity Score (PASDAS) (<span style="font-style:italic;">r</span> = 0.540, <span style="font-style:italic;">P</span> = 0.038) and PsASon13 (<span style="font-style:italic;">r</span> = 0.701, <span style="font-style:italic;">P</span> = 0.005), while no correlation was observed in <sup>18</sup>F-NaF PET/CT.<div class="boxTitle">Conclusion</div>The positivity rates of <sup>68</sup>Ga-FAPI- and <sup>18</sup>F-NaF PET/CT were different in patients with PsA in peripheral joints, entheses, and axial joints. The extent of joint involvement as shown in <sup>68</sup>Ga-FAPI PET/CT correlated with clinical and US variables as well as with disease activity.<div class="boxTitle">Trial registration</div>ClinicalTrials.gov, <a href="http://clinicaltrials.gov">http://clinicaltrials.gov</a>, NCT05686876.</span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Objectives</div>The objectives of this study were to evaluate the effectiveness of short message service (SMS) and/or email reminders in improving influenza vaccination coverage rates among RA patients treated with anti-TNF therapies, and to identify factors associated with vaccination.<div class="boxTitle">Methods</div>This study was a nested randomized controlled trial in the ART e-cohort, an ongoing French nationwide multicentre prospective cohort of RA patients treated with anti-TNF therapy. Patients were 1:1 randomized, with stratification on age. The intervention consisted of regular reminders via SMS and/or emails to get vaccinated against influenza during the vaccination campaign. At the end, all participants received a questionnaire. The primary outcome was influenza vaccination coverage. Secondary outcomes included the vaccination coverage before and after the COVID-19 pandemic, and factors associated with vaccination.<div class="boxTitle">Results</div>Between October 2021 and April 2022, 446 participants were randomized (224 to the intervention group and 222 to the control group). Among them, 325 (73%) reported their vaccination status and 221 (68%) were vaccinated against influenza: 116/158 (73%) in the intervention group, <span style="font-style:italic;">vs</span> 105/167 (63%) in the control group (relative risk 1.08; 95% CI 0.95–1.23). The vaccination coverage before and after the COVID-19 pandemic did not differ (72% <span style="font-style:italic;">vs</span> 72%; 95% CI −8% to 8%). Age ≥65 years [odds ratio (OR) 6.25; 95% CI 2.88–13.60] and previous influenza vaccination in the years before inclusion (OR 7.81; 95% CI 4.36–14.02) were associated with higher rates of vaccination<div class="boxTitle">Conclusion</div>SMS and/or e-mail reminders did not significantly improve influenza vaccination rates in our cohort. The COVID-19 pandemic did not substantially impact the influenza vaccination coverage. Our results might be counterbalanced by an already high vaccination coverage.<div class="boxTitle">Trial registration</div>ClinicalTrials.gov, <a href="http://clinicaltrials.gov">http://clinicaltrials.gov</a>, NCT05220423, NCT03062865.</span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Objectives</div>The aim of this work was to determine whether smartphone applications could support the self-management of RA and to investigate engagement and potential negative psychological effects with app-use.<div class="boxTitle">Methods</div>App-based Education and GOal-setting in RA (AEGORA) was a multicentre randomized controlled trial with 2:1:1 allocation to usual care or two versions of an app-based self-management intervention for RA. The 16-week programme involved patient education, goal-setting and remote monitoring of the Rheumatoid Arthritis Impact of Disease (RAID) instrument, either weekly or monthly depending on randomization. The primary end point was improvement in the Arthritis Self-Efficacy Scale (ASES) after 16 weeks. Secondary endpoints included non-inferiority regarding the Pain Catastrophizing Scale (PCS) and superiority regarding patient-reported physical activity, sleep quality and RAID. App engagement and RAID scores were analysed descriptively.<div class="boxTitle">Results</div>Overall, 122 patients were included: mean (<span style="text-transform:lowercase;font-variant:small-caps;">s</span>.<span style="text-transform:lowercase;font-variant:small-caps;">d</span>.) disease duration 12 (9) years, age 58 (11), 68% female, DAS28-CRP 2.4 (0.9). The intervention did not improve the ASES score over usual care (β 0.44, <span style="font-style:italic;">P</span> = 0.87). Non-inferiority was established for the PCS (β −0.95 [95% CI −3.30, +1.40] favouring the intervention). Other predefined outcomes did not differ. App retention steadily declined to 43% by 16 weeks. Although the RAID remained stable over time overall, 35% of app users reported ≥1 episode of clinically relevant worsening over 16 weeks.<div class="boxTitle">Conclusion</div>This app-based self-management intervention was not superior to usual care regarding self-efficacy improvement. However, remote symptom monitoring provided valuable insight and did not increase pain catastrophizing, alleviating concerns regarding the psychological impact of remote monitoring with apps.<div class="boxTitle">Trial registration number</div>clinicaltrials.gov, NCT05888181.</span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Objectives</div>Novel biomarkers are needed to guide therapy in idiopathic inflammatory myopathies (IIM). Expression of Siglec-1, a type I interferon biomarker, was examined in adult patients with IIM in relation to disease activity and treatment response.<div class="boxTitle">Methods</div>We analyzed PBMC samples from 19 newly diagnosed adult IIM patients who participated in a phase-2 pilot study on efficacy of intravenous immunoglobulin (IVIG) monotherapy, and from 9 healthy controls. Siglec-1 expression on monocytes was measured by flow cytometry before and after treatment, and was evaluated in relation to IIM subtype, physician global activity (PhGA) scores, manual muscle strength (MMT) and the total improvement score (TIS).<div class="boxTitle">Results</div>Diagnoses included dermatomyositis (DM; <span style="font-style:italic;">n</span> = 9), immune-mediated necrotizing myopathy (IMNM; <span style="font-style:italic;">n</span> = 5), non-specific/overlap myositis (NSM/OM; <span style="font-style:italic;">n</span> = 4) and antisynthetase syndrome (ASyS; <span style="font-style:italic;">n</span> = 1). All patients showed increased Siglec-1 expression at baseline. Relative median fluorescence intensity of Siglec-1 was highest in patients with DM. After 9 weeks, follow-up samples were available for 15 patients of whom 10 patients showed a decline in Siglec-1 expression. In DM, Siglec-1 correlated with disease activity (MMT; rs = −0.603, <span style="font-style:italic;">P</span> = 0.013 and PhGA; rs = 0.783, <span style="font-style:italic;">P</span> < 0.001) and with the TIS (rs = −0.786, <span style="font-style:italic;">P</span> = 0.036).<div class="boxTitle">Conclusion</div>Siglec-1 was increased in treatment-naive IIM patients and showed a decline after IVIG monotherapy. In DM, Siglec-1 expression correlated with relevant clinical measures. This underlines the dynamic role of type I IFN in IIM and the biomarker potential of Siglec-1, in particular in DM. These findings should be further validated in larger cohorts with longer follow-up.</span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Objectives</div>Although Behçet’s disease (BD) typically manifests in the second or third decade of life, initial symptoms may appear at a younger age. It may also take a longer time for the full disease phenotype to develop after the first symptom onset in paediatric patients. In this study, the objective was to assess the clinical course of paediatric-onset BD in young adult period.<div class="boxTitle">Methods</div>The files of 112 patients diagnosed with BD before the age of 18, selected from five tertiary clinics, were retrospectively examined. Patients with a follow-up of less than 6 months were excluded.<div class="boxTitle">Results</div>The study comprised 93 patients with paediatric-onset BD, of whom 64.5% (<span style="font-style:italic;">n</span> = 60) were male. The median age of diagnosis was 15 years (13–17). Major organ involvement was present in 49 (52.5%) patients. The most commonly affected organ was the eye (29%). Sixty-eight patients (73.1%) had follow-up data in adulthood. Forty patients had only mucocutaneous manifestations in the paediatric period. During follow-up in adulthood, 15 (53.3% were male) had new major organ involvement, at a mean of 10.1 (<span style="text-transform:lowercase;font-variant:small-caps;">s</span>.<span style="text-transform:lowercase;font-variant:small-caps;">d</span>.: 7.9) years after diagnosis. Twenty-eight patients (41.1%) experienced major organ involvement during the paediatric period. In follow-up during adulthood, 12 (42.8%) developed new major organ involvement and/or relapse of the same organ. Eighteen (26.5%) of 68 paediatric-onset BD patients had new major organ involvement, and 9 (13.2%) had a relapse during follow-up in adulthood.<div class="boxTitle">Conclusion</div>Our results showed that nearly one-third of paediatric BD patients have a new major organ involvement or a relapse in adulthood. Regular follow-up of paediatric BD patients in adulthood is essential for preventing long-term damage in this disease subset.</span>
<span class="paragraphSection"><span style="text-transform:lowercase;font-variant:small-caps;">Dear Editor</span>, We appreciate Lai <span style="font-style:italic;">et al</span>.’s interest [<a href="#keae626-B1" class="reflinks">1</a>] in our article, ‘Association between Colchicine Use and Adverse Cardiovascular Events in Patients with Gout: A Nationwide Nested Case-Control Study’ [<a href="#keae626-B2" class="reflinks">2</a>]. Colchicine, a well-established treatment for gout, has recently garnered attention for its potential cardiovascular benefits, as highlighted by recent promising randomized controlled trials. However, the primary preventive cardiovascular effects of colchicine, specifically in patients with gout, remain underexplored. Contrary to our initial expectations, our study showed an association between colchicine use and significantly higher odds of adverse cardiovascular outcomes in a nationwide, claims-based, nested case–control analysis. Our results should be interpreted with caution as they are real-world observational data that differ from the controlled settings of previous clinical trials in which colchicine showed significant benefits in secondary prevention of cardiovascular disease.</span>
<span class="paragraphSection"><span style="text-transform:lowercase;font-variant:small-caps;">Dear Editor</span>, We are writing in response to the recent study by Kim <span style="font-style:italic;">et al.</span> [<a href="#keae625-B1" class="reflinks">1</a>] reporting that colchicine use correlated with an increased risk of atherosclerotic cardiovascular disease (ASCVD) in people with newly diagnosed gout and without a prior history of ASCVD. We raise some considerations regarding the interpretation of the Kim <span style="font-style:italic;">et al.</span>’s findings.</span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Objectives</div>Systemic autoimmune rheumatic diseases (SARDs) are characterized by chronic inflammation. Reliable biomarkers are crucial for diagnosis, monitoring disease progression and therapeutic responses. This study explores serum syndecan-1 (SDC-1) as a biomarker for these conditions and its relationship with free light chain (FLC) levels.<div class="boxTitle">Methods</div>A retrospective analysis was performed on sera from 60 patients with rheumatoid arthritis (RA) and from 60 with systemic lupus erythematosus (SLE), alongside 50 healthy donors (HD). Κ- and λ- FLCs were determined by turbidimetric assay, while SDC-1 levels were determined by ELISA. Kruskal–Wallis test, Wilcoxon Mann–Whitney <span style="font-style:italic;">U</span> test, multivariable linear regression and Spearman’s correlation were employed to compare biomarker levels across groups and to explore correlations.<div class="boxTitle">Results</div>SDC-1, κ-FLC and λ-FLC were significantly increased in RA and SLE patients compared with HD (<span style="font-style:italic;">P</span> < 0.001), while no significant differences in the κ/λ ratio were observed among the groups (<span style="font-style:italic;">P</span> = 0.4). A significant difference in subject age was also identified. However, multivariate regression analysis indicated that RA and SLE are significantly associated with the levels of these markers, with minimal confounding by age. A significant correlation was observed separately in all groups between the FLC markers. Conversely, no correlation was detected between SDC-1 and FLCs, nor between these markers and age or disease activity indices.<div class="boxTitle">Conclusion</div>Elevated serum levels of FLCs and SDC-1 in RA and SLE patients compared with HD underscore their potential as biomarkers for SARDs. The findings also suggest sustained plasma cell activation, supporting the multifaceted role of SDC-1 in the pathogenesis of SARDs.</span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Objectives</div>To investigate the association between depression and anxiety and the inability to achieve remission in RA and PsA patients. In addition, the association between depressive and anxiety symptoms and disease activity components was explored.<div class="boxTitle">Methods</div>A total of 400 RA and 367 PsA patients from the tREACH and DEPAR were included, respectively. Patients had a possible depression or anxiety disorder if they scored >7 on the Hospital Anxiety and Depression Scale (HADS). Remission was defined as DAS44 <1.6 in RA and DAPSA ≤ 4 in PsA. Mixed models were used to assess the association between depression/anxiety, at any timepoint during 2 years, and remission during 2 years, and to explore which disease activity components are most influenced by depression/anxiety.<div class="boxTitle">Results</div>At baseline, 20% of RA patients had a possible depression and 30% a possible anxiety disorder. In PsA this was 18% and 23%. After adjustment for concurrent anxiety symptoms, depression was associated with a lower odds of achieving remission during 2 years of follow-up [OR 0.45 (95%CI 0.25–0.80) for RA and OR 0.24 (95%CI 0.08–0.71) for PsA]. Anxiety was not associated with remission after adjustment for concurrent depression symptoms. The presence of depression/anxiety was associated with higher tender joint count, worse general health, more pain and slightly elevated inflammation markers, but not with more swollen joints in both RA and PsA.<div class="boxTitle">Conclusion</div>The presence of depressive symptoms in RA and PsA patients at baseline or during follow-up was associated with a lower likelihood of achieving remission. Healthcare professionals should, therefore, be aware of symptoms of depression.</span>
<span class="paragraphSection"><span style="text-transform:lowercase;font-variant:small-caps;">Dear Editor</span>, I read with great interest the manuscript entitled ‘Real-world outcomes of a dedicated fast-track polymyalgia rheumatica clinic’. Cowley <span style="font-style:italic;">et al</span>. confirmed that PMR fast track clinic (PMR FTC) might reduce the burden of this disease. Indeed, PMR exerts a profound impact on patients’ lives in multiple aspects, glucocorticoids (GCs)-related adverse events and quality of life, among these [<a href="#keae617-B1" class="reflinks">1</a>].</span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Objectives</div>Stage ≥3 chronic kidney disease (CKD) affects ∼25% of people with gout. The effects of urate-lowering therapy (ULT) on CKD incidence and progression have remained inconclusive. Here, we assessed the impact of a gout ULT clinic intervention using artificial intelligence (AI) on CKD incidence and achievement of serum urate (SU) target.<div class="boxTitle">Methods</div>An observational study compared propensity score (PS)-matched gout cohorts from an AI-based Gout Intelligent Management System (GIMS) and a standard Electronic Medical Records system (EMRS) clinic database. The GIMS included a mobile application, data fusion interface and modules for expert consultation and laboratory results management. All patients had gout and a starting estimated glomerular filtration rate >60 ml/min. Using a 1:2 PS-matched cohort study design, we assessed the impact of the AI-based system on CKD outcomes and ULT effectiveness over 4 years of follow-up.<div class="boxTitle">Results</div>Compared with EMRS, GIMS was associated with reduced incidence of CKD stage ≥3. Specifically, 169/4117 new-onset CKD stage ≥3 (incidence 4.1 per 100 person-years) with GIMS compared with 164/2128 with EMRS (incidence 7.7 per 100 person-years) during follow-up. More participants achieved SU <6.0 mg/dl with GIMS versus EMRS during follow-up (49.8% vs 25.9%, <span style="font-style:italic;">P</span> < 0.001).<div class="boxTitle">Conclusion</div>Application of the artificial intelligence-based Gout Intelligent Management System was associated with lower incidence of chronic kidney disease stage ≥3 and superior target serum urate achievement in people with gout. The Gout Intelligent Management System represents a novel approach to improve real-world renal outcomes and urate-lowering therapy success in gout.</span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Objective</div>This study aimed to elucidate which bio-naïve patients with RA are suitable for treatment with CTLA4-Ig.<div class="boxTitle">Methods</div>This study enrolled 953 patients with RA who were administered their first biological DMARD (CTLA4-Ig, <span style="font-style:italic;">n </span>=<span style="font-style:italic;"> </span>328; tumour necrosis factor inhibitor [TNFi], <span style="font-style:italic;">n </span>=<span style="font-style:italic;"> </span>625) from July 2013 to August 2022. The primary outcome was the Clinical Disease Activity Index (CDAI) remission rate at week 24 in each group, adjusted using propensity score (PS)-based inverse probability of treatment weighting (IPTW).<div class="boxTitle">Results</div>After minimizing selection bias using PS-based IPTW, the CDAI remission showed no significant difference between the CTLA4-Ig and TNFi groups (<span style="font-style:italic;">P</span> = 0.464). Multivariable logistic regression analysis identified low baseline HAQ–Disability Index (DI) scores as a contributing factor to the CDAI remission rate at week 24 in both groups, along with high baseline ACPA levels in the CTLA4-Ig group. However, among patients with high baseline HAQ-DI scores and low baseline ACPA levels (≦57.2), the CDAI remission rate was significantly higher in the TNFi group (29.8%) compared with the CTLA4-Ig group (5.9%, <span style="font-style:italic;">P</span> < 0.0001). Among patients with high baseline HAQ-DI scores and ACPA levels (>57.2), the CDAI remission rate was significantly higher in the CTLA4-Ig group (35.6%) compared with the TNFi group (22.1%, <span style="font-style:italic;">P</span> = 0.0057).<div class="boxTitle">Conclusion</div>Bio-naive RA patients with low HAQ-DI scores showed high treatment efficacy with no significant difference between CTLA4-Ig and TNFi. Among patients with high baseline HAQ-DI scores, TNFi and CTLA4-Ig were more likely to be effective in those with lower and higher baseline ACPA levels, respectively.</span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Objective</div>Developing knee osteoarthritis (OA) treatments is challenging due to assessing pain and joint structure outcomes within a highly heterogeneous disease. Lorecivivint (LOR), an intra-articular CLK/DYRK inhibitor, modulates Wnt and inflammatory pathways. This review analysis of LOR 0.07 mg trial data aims to describe the potential impact of baseline joint structure on OA pain response.<div class="boxTitle">Methods</div>Two Phase 2 and two Phase 3 trials enrolled knee OA patients with Kellgren-Lawrence (KL) Grades 2–3 and Pain Numeric Rating Scale [NRS (0–10)] ≥ 4 to ≤8 in their target knee. Cumulative frequency distribution plots by KL grade summarized the percentages of patients with medial joint space width (medial JSW) < 3 mm. Osteoarthritis Research Society International Joint Space Narrowing grades and treatment responses in trials capturing Pain NRS were similarly summarized. Pain outcome changes were estimated using baseline adjusted ANCOVA.<div class="boxTitle">Results</div>Compared with phase 2 trials, the phase 3 trials had an increased proportion of patients with baseline medial JSW <3 mm. LOR demonstrated beneficial treatment effects vs placebo in KL 2 subgroups, which were found to have higher proportions of baseline medial JSW >3 mm, apart from one Phase 3 trial with advanced structural knee OA.<div class="boxTitle">Conclusion</div>Baseline medial JSWs were heterogeneous across trials despite KL inclusion criteria. LOR demonstrated greater symptomatic improvements in patients with less structurally advanced disease, indicative of an association between OA structural damage and pain. Early treatment interventions may improve outcomes and provide insight for future OA trial inclusion criteria development.<div class="boxTitle">Trial registration</div>OA-02, NCT02536833; OA-04, NCT03122860; OA-10, NCT04385303; OA-11, NCT03928184.</span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Objectives</div>This study aimed to evaluate the therapeutic efficacy of telitacicept based on the conventional treatment in adults with idiopathic inflammatory myopathy (IIM), focusing on its impact on clinical manifestations.<div class="boxTitle">Methods</div>IIM patients who had been treated with telitacicept for at least 3 months based on the conventional treatment from January 2023 to January 2024 were included in this study. The clinical response to telitacicept was determined based on the ACR/EULAR criteria for minimal, moderate and major improvement in the Total Improvement Score. Disease activity was monitored using core set measures, while myositis damage was assessed with established assessment tools. The Manual Muscle Test for eight muscle groups (MMT-8) was used to assess the muscle performance.<div class="boxTitle">Results</div>A total of 11 patients administered with telitacicept (160 mg per week) were included in this study. Post-treatment assessments revealed improvements in all patients according to ACR/EULAR criteria. Notably, there was a significant reduction in the prednisone dosage from baseline to last visit [27.05 (12.47) to 12.05 (7.32) mg; <span style="font-style:italic;">P</span> < 0.005]. An enhancement was observed in the MMT-8 score [which improved from 109.18 (14.18) to 137.64 (15.28); <span style="font-style:italic;">P</span> < 0.005], and there was a reduction in creatine kinase level [from 2670.27 (2675.00) to 561.09 (754.09) U/l; <span style="font-style:italic;">P</span> < 0.05].<div class="boxTitle">Conclusion</div>Telitacicept demonstrated effectiveness in treating refractory inflammatory myopathy, contributing to a significant reduction in steroid dosage among the patients. These findings highlight the potential of telitacicept as a valuable therapeutic option in the management of IIM.</span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Objectives</div>Cardiovascular (CV) disease is the leading cause of death among patients with SLE. This study aimed to compare the performance of QRESEARCH risk estimator version 3 (QRISK3) and the Systematic Coronary Risk Evaluation-2 (SCORE2) scores to identify SLE patients at high risk of CV events, as indicated by the presence of carotid plaques.<div class="boxTitle">Methods</div>Subclinical atherosclerosis was evaluated using carotid US in 365 SLE patients. QRISK3 and SCORE2 were calculated. The relationship between these scores and the presence of carotid plaques was analysed by treating the scores as continuous and categorical variables, as well as separately and in combination. Logistic regression and area under the receiver operating characteristic curve (AUC) analyses were used to assess their predictive accuracy.<div class="boxTitle">Results</div>The discriminatory capacity of QRISK3, with an AUC of 0.770 (95% CI 0.720, 0.821), and SCORE2, with an AUC of 0.800 (95% CI 0.753, 0.843), for carotid plaque was similar, with no statistically significant difference (<span style="font-style:italic;">P</span> = 0.070). However, when examining the association of both calculators considered continuously and together with their interaction, the discriminatory capacity of this combination was significantly greater than that of QRISK3 alone (<span style="font-style:italic;">P</span> = 0.034) but did not differ from SCORE2 (<span style="font-style:italic;">P</span> = 0.71).<div class="boxTitle">Conclusion</div>QRISK3 and SCORE2 are equally reliable predictors of carotid plaques in SLE patients. The combination of both calculators offers significantly better discrimination than QRISK3 alone but shows no significant difference when compared with SCORE2 alone. Therefore, SCORE2 alone, without the need for additional tools, can be used to identify patients with SLE who are at high risk of CV events.</span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Objective</div>The objective of this study was to evaluate temporal and regional variation in biologic and targeted synthetic DMARD (b/tsDMARD) initiation for RA in England and Wales.<div class="boxTitle">Methods</div>An observational cohort study was conducted for people with RA enrolled in the National Early Inflammatory Arthritis Audit (NEIAA) between May 2018 and April 2022 who had 12-month follow-up data available. Temporal trends in escalation to b/tsDMARDs within 12 months of initial rheumatology assessment were explored, including comparisons before and after publication (July 2021) of national guidelines that lowered the threshold for b/tsDMARD initiation to include moderate-severity RA. Case-mix–adjusted, mixed-effects regression was used to evaluate regional and hospital-level variation in b/tsDMARD initiation.<div class="boxTitle">Results</div>Of 6098 RA patients with available follow-up, 508 (8.3%) initiated b/tsDMARDs within 12 months of initial assessment. b/tsDMARD escalation increased marginally towards the end of the study period (9.2% in May 2021/22); however, no significant differences were evident after guidelines were published permitting b/tsDMARD use for moderate-severity RA. The proportion of individuals escalated to b/tsDMARDs varied considerably between regions, ranging from 5.1% in Wales to 10.7% in North-West England. Following case-mix adjustment, the intraclass correlation (ICC) for hospitals within regions was 0.17, compared with a between-region ICC of 0.0, suggesting that the observable regional variation reflected hospital-level differences rather than systematic differences between regions themselves.<div class="boxTitle">Conclusion</div>There is marked variation in escalation to b/tsDMARDs for people newly diagnosed with RA throughout England and Wales, despite a universal health-care system. These disparities must be addressed if we are to deliver equitable access to b/tsDMARDs, regardless of geography.</span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Objective</div>SSc is a complex disease that affects various target organs, making it difficult to assess response and determine remission or relapse. A baseline neutrophil-to-lymphocyte ratio (NLR) >2.95 is associated with severe progressive skin and lung disease and decreased 5-year survival in SSc. However, it is unknown whether NLR changes in response to treatment. To retrospectively evaluate NLR changes as a biomarker for treatment response in SSc.<div class="boxTitle">Methods</div>Progressive diffuse SSc patients who were treated with autologous haematopoietic stem cell transplantation (AHSCT group), with combination therapy of rituximab and MMF (combination group) or chimeric antigen receptor-T-cell (CAR-T) therapy group, were recruited along with healthy controls (HC group). NLR, modified Rodnan Skin Score (mRSS) and forced vital capacity (FVC)% predicted were repeatedly assessed over 2 years.<div class="boxTitle">Results</div>Fifteen patients were recruited in the AHSCT group, 15 in the combination group and 6 patients in the CAR-T group. Baseline mean NLR was high (>2.95) in AHSCT, combination groups and CAR-T compared with HC. All treatment arms showed a statistically significant decrease in mRSS values and an increase in FVC% at each time point up to 12 months. In a linear mixed model, NLR significantly decreased up to 24 months only in the AHSCT group. NLR correlated with mRSS and FVC exclusively in the AHSCT group. NLR increased above 3 in two patients who experienced a relapse after AHSCT.<div class="boxTitle">Conclusion</div>NLR is a simple biomarker that correlated with outcome measures in SSc following AHSCT but not with conventional therapy or CAR-T therapy. It is suggested that a decrease in NLR following AHSCT may indicate remission, whereas an increase may be associated with exacerbation. Further research is needed to validate these novel findings.</span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Objectives</div>The impact of individual biological/targeted synthetic DMARD (b/tsDMARD) on kidney function in patients with RA remains unclear. This study aimed to determine the comparative effects of b/tsDMARDs on chronic kidney disease (CKD) incidence in patients with RA.<div class="boxTitle">Methods</div>This multicentre cohort study included patients with RA who had baseline estimated glomerular filtration rate (eGFR) of ≥60 ml/min/1.73 m<sup>2</sup> and started a TNF inhibitor (TNFi), cytotoxic T-lymphocyte-associated antigen-4-Ig (CTLA4-Ig), interleukin-6 receptor inhibitor, or Janus kinase inhibitor (JAKi) in Japan. Multiple propensity score-based inverse probability weighting (IPW) was used to adjust confounders. The incidence of CKD was compared among b/tsDMARDs using IPW mixed-effect Cox proportional hazards models and linear mixed-effect models with IPW-examined trajectories of eGFR.<div class="boxTitle">Results</div>Among 2187 patients with 3068 treatment courses and up to 11 years of follow-up, CKD occurred in 275 cases. Compared with the CTLA4-Ig group, the TNFi group had a significantly lower CKD incidence [hazard ratio (HR) 0.67, 95% CI 0.46–0.97, <span style="font-style:italic;">P</span> = 0.04], whereas the JAKi group had a significantly higher incidence (HR 2.16, 95% CI 1.23–3.79, <span style="font-style:italic;">P</span> = 0.01). The trajectory of eGFR was significantly greater in the JAKi group than in the CTLA4-Ig group (CTLA4-Ig: −1.28 ml/min/1.73 m<sup>2</sup>/year, JAKi: −2.29 ml/min/1.73 m<sup>2</sup>/year, <span style="font-style:italic;">P</span> < 0.001).<div class="boxTitle">Conclusions</div>TNFi use was associated with reduced CKD incidence, whereas JAKi showed a less protective association for kidney function in patients with RA.</span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Objective</div>The objective of this study was to explore the aetiologies and contributing factors of synovial and tenosynovial involvement in SSc, as well as to assess the phenotype of patients with these synovial and tenosynovial features.<div class="boxTitle">Methods</div>One hundred and seventy-one SSc patients with hand manifestations (either vascular, skin or joint manifestations) who underwent standard X-rays of both hands and hand US, were included. Two independent evaluators recorded the presence or absence of acro-osteolysis, calcinosis, microcrystalline and degenerative rheumatisms, including osteophytosis on X-rays. The presence of synovitis and tenosynovitis (active or fibrotic) was assessed through US by a third evaluator, blinded for X-ray parameters.<div class="boxTitle">Results</div>In multivariate analysis, the characteristics associated with active synovitis and tenosynovitis were CRP > 10 mg/l (<span style="font-style:italic;">P</span> = 0.013), fibrotic tenosynovitis on US (<span style="font-style:italic;">P = </span>0.005), anti-RNA polymerase III antibodies (<span style="font-style:italic;">P = </span>0.043) and poly-osteophytosis on hand X-rays (<span style="font-style:italic;">P = </span>0.001). After exclusion of patients with RA (<span style="font-style:italic;">n</span> = 5) and/or poly-osteophytosis (<span style="font-style:italic;">n</span> = 53), 14 remaining patients (12.7%) had active synovitis and/or tenosynovitis on US. In multivariate analyses, parameters associated with active synovitis and/or tenosynovitis in this selected population were scleroderma renal crisis (<span style="font-style:italic;">P = </span>0.012) and fibrotic tenosynovitis on US (<span style="font-style:italic;">P</span> < 0.001).<div class="boxTitle">Conclusion</div>Our study confirms that osteophytosis is a significant contributor of joint involvement in SSc patients based on real life data. After exclusion of potential confounders, >10% of SSc patients still had active synovitis and/or tenosynovitis on US, providing indirect evidence for the existence of a specific SSc-related synovial and/or tenosynovial involvement.</span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Objectives</div>Increased circulating levels of CXCL13 reflect synovial production and indicate immune dysregulation in patients with RA. Here we tested whether CXCL13 predicts response to first-line treatment with MTX in patients with early RA, independently and in association with ACPA and IgM-RF.<div class="boxTitle">Methods</div>A prospective cohort of 243 early RA patients undergoing treat-to-target with MTX was evaluated. CXCL13, ACPA and IgM-RF were determined on baseline sera. Short-term variations of CXCL13 were measured after 2 months. The association of high CXCL13 (≥100 pg/ml) with disease remission after 6 months and escalation to second-line therapies within year 2 was evaluated in the total population and in ACPA subgroups separately.<div class="boxTitle">Results</div>High levels of CXCL13 were found in 53.6% of ACPA-positive and 31.5% of ACPA-negative patients, with minimal association with disease activity and RF. Serum CXCL13 remained stable after 2 months. High baseline CXCL13 independently predicted failure to achieve remission and more frequent requirement of second-line treatment in ACPA-positive patients, with adjusted odds ratios (ORs) in the range of 0.17–0.49 for remission and 6.75 for second-line treatment. In ACPA-negative patients with high CXCL13, remission occurred at the expense of higher doses of MTX, and levels of CXCL13 predicted MTX escalations with an adjusted OR (95% CI) of 2.69 (1.35–5.34).<div class="boxTitle">Conclusions</div>High serum levels of CXCL13 identify a subgroup of RA patients who are more refractory to first-line treatment with MTX. CXCL13 appears a promising biomarker of response to MTX in both ACPA-positive and -negative early RA.</span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Objectives</div>Idiopathic retroperitoneal fibrosis (iRPF) can lead to irreversible kidney damage. This study aimed to investigate predictors of irreversible renal dysfunction in patients with iRPF.<div class="boxTitle">Methods</div>Eighty-three patients with newly diagnosed iRPF were enrolled between January 2010 and September 2022 at Zhongshan Hospital of Fudan University, including 60 in the training set and 23 in the validation set. They were regularly contacted or followed up via outpatient examinations by specialist doctors, who documented their condition and treatment progress. Predictors of irreversible renal dysfunction were identified using univariate and multivariate regression, logistic model, and receiver operating curve analyses.<div class="boxTitle">Results</div>In the training set, over a median follow-up of 29 months, 16.7% of patients had an estimated glomerular filtration rate (eGFR) of <60 ml/min/1.73 m<sup>2</sup> at the last follow-up, and 25% had hydronephrosis or required prolonged double-J stents. A prognostic score was developed by assigning 1, 1, and 2 points for peripheral CD19<sup>+</sup> B cells <9.3%, serum creatinine (sCr) ≥120 µmol/L, and no response at 6 months, respectively. A score of ≥2 for predicting irreversible renal dysfunction had sensitivity and specificity of 100% and 92%, respectively. In the validation set, 21.7% of patients suffered from irreversible renal dysfunction. The sensitivity and specificity for predicting irreversible renal dysfunction were 100% and 94.4%, respectively.<div class="boxTitle">Conclusions</div>A prognostic score based on factors including CD19<sup>+</sup> B cells <9.3% and sCr ≥120 µmol/L at baseline, and no response at 6 months, is suitable for predicting irreversible renal dysfunction in iRPF.</span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Objectives</div>Patients with immune-mediated rheumatic diseases (IMRDs) face an elevated risk of varicella-zoster virus infection (VZV) and herpes zoster (HZ). Treatment with immunosuppressors further increases the risk. A new recently approved adjuvant recombinant inactive vaccine offers safe protection against HZ. However, limited data exist on the efficacy of this new vaccine in patients with IMRDs treated with JAK inhibitors (JAK-i). We aimed to characterize B- and T-cell immune responses elicited by the HZ recombinant subunit vaccine in patients with IMRDs under treatment with JAK-i, and to identify factors that might be associated with reduced immunogenicity, and therefore reduced protection.<div class="boxTitle">Methods</div>We investigated humoral and cellular CD4 and CD8 immune responses following a two-dose regimen of the recombinant inactive vaccine in 43 patients with rheumatic diseases treated with different JAK-i. The responses were compared with age, gender and disease-matched healthy controls.<div class="boxTitle">Results</div>Patients with IMRDs treated with JAK-i showed reduced seroconversion rate (63% vs. 100% and lower VZV IgG titres (1222 ± 411 vs. 3048 ± 556, <span style="font-style:italic;">P</span> < 0.0001) as compared with healthy controls. Functional T CD4 (IL-2 plus IFN-γ secretion) and T CD8 (granzyme A and/or granzyme B secretion) immune responses were also significantly diminished in IMRD patients. Negative correlation was found between VZV antibody titres and age, specific treatments (baricitinib, tofacitinib, upadacitinib), cumulative MTX and glucocorticoid doses, history of multiple DMARDs and treatment duration with JAK-i. Functional T-CD4 responses but not functional T-CD8 responses also showed similar negative correlations. Positive associations were observed between functional T-CD4 and T-CD8 responses.<div class="boxTitle">Conclusions</div>Our study provides valuable insights into the immune responses elicited by the recombinant inactive vaccine in patients with IMRDs treated with JAK-i. In these patients we have observed a broad impact on the adaptive humoral and cellular immune responses, suggesting a potential reduction in protection against HZ infection and VZV reactivation.</span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Objectives</div>The objectives of this study were to compare fatigue in a large multinational SSc cohort with general population data and identify associated sociodemographic, lifestyle and SSc disease factors.<div class="boxTitle">Methods</div>Scleroderma Patient-centered Intervention Network Cohort participants completed the Patient-Reported Outcomes Measurement Information System-29 v2.0 fatigue domain. T-scores were compared with the USA general population (mean = 50; <span style="text-transform:lowercase;font-variant:small-caps;">s</span>.<span style="text-transform:lowercase;font-variant:small-caps;">d</span>. = 10). Multivariable linear regression was used to assess associations with sociodemographic, lifestyle, and disease-related variables.<div class="boxTitle">Results</div>Among the 2385 participants [mean age 54.9 (<span style="text-transform:lowercase;font-variant:small-caps;">s</span>.<span style="text-transform:lowercase;font-variant:small-caps;">d</span>. = 12.6) years, 87% female, 38% dcSSc], the mean fatigue T-score was 54.6 (<span style="text-transform:lowercase;font-variant:small-caps;">s</span>.<span style="text-transform:lowercase;font-variant:small-caps;">d</span>. = 11.0); 438 (18%) reported mild fatigue, 641 (27%) moderate fatigue, and 180 (8%) severe fatigue. Fatigue was independently associated with sociodemographic factors age [−0.10 points per year, (95% CI −0.14, −0.07)], male sex [−1.67 points, (−2.96, −0.37)], non-married status [0.97 points (0.04, 1.89)] and country [reference USA; France −2.35 points (−3.48, −1.21) and UK 2.38 points (0.80, 3.97)], and lifestyle factors smoking [4.16 points (2.52, 5.80)], alcohol consumption [−0.18 points per drink per week (−0.28, −0.07)] and BMI [0.34 points per unit (0.27, 0.42)]. Fatigue was associated with disease-related factors, including gastrointestinal involvement [4.21 points (2.99, 5.43)], digital ulcers [1.51 points, (0.25, 2.77)], moderate small joint contractures (1.41 points [0.13, 2.69]), RA [4.34 points (2.37, 6.31)] and SS [1.89 points (0.23, 3.55)]. When pain was included in the model, its association was large [2.19 points (2.03, 2.34)], and interstitial lung disease was also associated [1.21 points (0.42, 2.00)].<div class="boxTitle">Conclusion</div>In people with SSc, fatigue scores were substantially higher than in the general population and associated with multiple disease factors, including gastrointestinal involvement, several painful disease manifestations, and lung involvement.</span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Objectives</div>To maximize the cost-effectiveness of tofacitinib, one of the Janus kinase inhibitors, there is an unmet need to identify predictors of therapeutic response. Utilizing phage immunoprecipitation sequencing (PhIP-Seq), we aim to identify peptide biomarkers for predicting good response to tofacitinib in rheumatoid arthritis (RA) patients.<div class="boxTitle">Methods</div>We enrolled 106 patients who had received 24-week tofacitinib therapy, including 12 patients undergoing PhIP-Seq analysis in the discovery stage and 94 patients validated with enzyme-linked immunosorbent assay (ELISA) in the replication stage. Disease activity was assessed using the 28-joint disease activity score-erythrocyte sedimentation rate, and therapeutic response was evaluated using EULAR response criteria. Plasma levels of caspase-1 and IL-18 were determined using ELISA.<div class="boxTitle">Results</div>PhIP-Seq analysis identified antibodies to sucrose non-fermenting-related kinase (SNRK) and HUWE1 (ubiquitin E3 ligase) as peptide biomarkers for discriminating good responders from the non-good responders. Using ELISA for validation on another cohort, an optimal cut-off value of anti-SNRK antibody for predicting good response was 0.381, with AUC 0.823, specificity 80.6% and sensitivity 78.1% (<span style="font-style:italic;">P</span> = 3.01E-07), and anti-HUWE1 antibody at 0.362, with AUC 0.740, specificity 74.2% and sensitivity 62.5% (<span style="font-style:italic;">P</span> < 0.001). Plasma levels of anti-SNRK and anti-HUWE1 antibodies were positively correlated with levels of caspase-1 and IL-18 (both <span style="font-style:italic;">P</span> < 0.05). Multivariate logistic regression analysis revealed anti-SNRK antibody as a significant predictor of good therapeutic response. After tofacitinib therapy, anti-SNRK antibody levels significantly declined in good responders, but not in non-good responders.<div class="boxTitle">Conclusion</div>We identify two peptide antibodies, anti-SNRK and anti-HUWE1 antibodies, as pretreatment predictors of good therapeutic response to tofacitinib in RA patients.</span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Objectives</div>Proteinuria is a marker of lupus nephritis (LN) activity and damage. We aimed to explore the impact of baseline proteinuria level on long-term outcomes.<div class="boxTitle">Methods</div>We included 249 patients diagnosed with their first biopsy-proven LN. We divided patients based on baseline proteinuria into low-level (≤1 g/day, group 1; 62 patients), moderate-level (>1 and <3 g/day, group 2; 90 patients) and high-level proteinuria (≥3 g/day, group 3; 97 patients). Outcomes included complete proteinuria recovery (CPR) at 1 year, an adverse composite outcome (ESKD, a sustained ≥40% decline in eGFR, or death) and LN flares. Cox proportional hazard models were used to examine the association between baseline characteristics and long-term outcomes.<div class="boxTitle">Results</div>At baseline, the median [IQR] age was 33.2 [26.4, 42.4] years; median proteinuria level was 2.2 [1.0, 3.8] g/day. A total of 177 (71%) patients had proliferative lesions on biopsy; 59.7% in group 1, 78.9% in group 2 and 71.4% in group 3. The rate of achievement of CPR at 1 year was highest for group 1 and lowest for group 3. For long-term outcomes (median follow-up 8.4 years), the frequency of the adverse composite outcome was 27.4%, 26.7% and 48.5% in groups 1, 2 and 3, respectively; <span style="font-style:italic;">P = </span>0.003. The corresponding frequency of flares was 27.4%, 38.2% and 61.9%, respectively; <span style="font-style:italic;">P</span> < 0.001. In the multivariable model for factors associated with long-term outcomes, there was no significant difference between groups 1 and 2; group 3 was associated with the worst prognosis.<div class="boxTitle">Conclusions</div>Low-level proteinuria is commonly associated with proliferative LN and adverse long-term outcomes.</span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Objectives</div>To assess the prevalence and clinical significance of autoantibodies against lysobisphophatidic acid (aLBPA) in patients with APS.<div class="boxTitle">Methods</div>We conducted a retrospective analysis involving 91 patients with persistent conventional aPLs: 60 patients with at least one clinical event of APS (symptomatic group) and 31 without (asymptomatic group), as well as 33 aPL-negative controls. Detection of aLBPA in serum samples was performed using an enzyme-linked immunosorbent assay (ELISA) specifically designed for this study.<div class="boxTitle">Results</div>The prevalence of aLBPA is significantly higher in patients with persistent aPL than that of the control group (<span style="font-style:italic;">P</span> < 0.0001). Among patients with persistent aPL, our findings reveal a significantly higher prevalence of aLBPA in asymptomatic patients compared with their symptomatic counterparts (<span style="font-style:italic;">P</span> = 0.027). Notably, patients positive for IgG aPL alone demonstrated a greater likelihood of presenting clinical events suggestive of APS.<div class="boxTitle">Conclusion</div>The combined assay of aLBPA and conventional aPL could be used to stratify patients with persistent aPL. This combined approach could serve as a valuable tool in the management of this complex autoimmune disease, particularly in guiding decisions regarding the initiation of primary thromboprophylaxis in asymptomatic patients with persistent aPL.</span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Objectives</div>Awareness of paediatric-specific predictors of damage in childhood lupus is needed to inform mitigation measures. The objective of this study was to ascertain how clinical and demographic variables correlate with damage accrual and identify predictors of damage.<div class="boxTitle">Methods</div>This analysis included UK JSLE Cohort Study participants. Univariable and multivariable Prentice-Williams-Peterson models investigated how demographic and clinical factors influenced the hazards of new damage. Analyses were performed across the entire cohort, in patients with minimal disease activity marked by a time-adjusted average SLEDAI-2K score (AMS) of ≤2, in patients with low activity (AMS of ≤4), patients with moderate-to-high activity (AMS of >4) and patients with no CS use.<div class="boxTitle">Results</div>Within the entire cohort (<span style="font-style:italic;">n</span> = 430), factors associated with damage included: any methylprednisolone [hazard ratio, HR 2.20 (CI 1.33–3.62)], time-adjusted mean Physician’s Global Assessment (PGA) [HR 2.87 (CI 1.48–5.56)] and AMS score [HR 1.13 (CI 1.03–1.24), all <span style="font-style:italic;">P < </span>0.05]. Within the low activity subgroup, any methylprednisolone [HR 2.61 (CI 1.04–6.53)] and time-adjusted mean PGA [HR 3.41 (CI 1.52–7.76)] were associated with damage (both <span style="font-style:italic;">P < </span>0.05). Within the moderate-to-high activity subgroup, any methylprednisolone [HR 2.29 (CI 1.31–4.00)], time-adjusted mean PGA [HR 2.66, (CI 1.20–5.87)] and AMS score [HR 1.15 (CI 1.03–1.29)] were predictive of damage (all <span style="font-style:italic;">P < </span>0.05). Baseline organ damage was predictive of subsequent damage accrual in the minimal disease activity subgroup [HR 1.33 (CI 1.78–8.08)] and the no CSs subgroup [HR 3.64 (CI 1.83–7.24), both <span style="font-style:italic;">P < </span>0.005].<div class="boxTitle">Conclusion</div>Disease activity levels (AMS/PGA) and proxy indicators (methylprednisolone exposure, baseline damage) were found to be key predictors of damage accrual. This highlights the importance of practical strategies, such as treat-to-target, for reducing disease activity and long-term treatment toxicity.</span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Objectives</div>To determine whether current MRI could detect superficial cartilage lesions that are observed in patients with knee pain for whom arthroscopy was indicated for therapeutic reasons or when the cause of pain was unclear.<div class="boxTitle">Methods</div>Adult patients with knee pain lasting more than 3 months, scheduled for a therapeutic/diagnostic arthroscopy, were recruited. Demographic and clinical data, pain assessment, MRI imaging and observations of cartilage damage in the medial femoral condyle during arthroscopic procedure were documented. Patients were categorized based on the presence of cartilage damage assessed via MRI and/or direct visualization. Concordance between these assessments and its variation with age and patient-reported pain were examined.<div class="boxTitle">Results</div>Out of the 95 patients recruited, 48 exhibited lesions in the medial femoral condyle (MFC) during arthroscopic examination, while only 24 of them showed lesions on the MRI scans. The thickness of the cartilage in the MFC was significantly lower in patients with cartilage damage detected by MRI compared with those without. Among patients with cartilage lesions identified during arthroscopy, those also showing lesions on the MRI had lower cartilage thickness and higher Outerbridge score than those without lesions on the MRI. Patients with detectable cartilage damage on the MRI were significantly older and reported higher levels of pain than those with damage detected only by arthroscopic examination.<div class="boxTitle">Conclusion</div>Despite significant technological advancements in MRI, arthroscopy still proves superior in identifying mild structural cartilage lesions that are not identifiable by this technique.</span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Objective</div>Evaluate guselkumab efficacy, an anti-interleukin-23p19-subunit antibody, in patients with active psoriatic arthritis (PsA) and inadequate response to 1 or 2 tumour necrosis factor inhibitors (TNFi-IR), utilizing composite indices assessing disease activity across disease domains.<div class="boxTitle">Methods</div>In the Phase IIIb COSMOS trial, 285 adults with TNFi-IR PsA were randomized (2:1) to receive guselkumab 100 mg or placebo at Week (W)0, W4, then every 8 weeks through W44. Patients receiving placebo crossed over to guselkumab at W24. In this <span style="font-style:italic;">post hoc</span> analysis, composite indices evaluated included the Disease Activity Index for Psoriatic Arthritis (DAPSA), Disease Activity Score 28 (DAS28), Psoriatic Arthritis Response Criteria (PsARC), Psoriatic Arthritis Disease Activity Score (PASDAS), GRAPPA Composite score (GRACE), modified Composite Psoriatic Disease Activity Index (mCPDAI), minimal disease activity (MDA), and very low disease activity (VLDA). Through W24, treatment failure rules were applied. Through W48, non-responder imputation was used for missing data.<div class="boxTitle">Results</div>Greater proportions of guselkumab- than placebo-randomized patients achieved composite index endpoints relating to low disease activity (LDA; 14.8–52.4% <span style="font-style:italic;">vs</span> 3.1–28.1%) or remission (3.7–5.3% <span style="font-style:italic;">vs</span> 0.0–2.1%) at W24. Among guselkumab-randomized patients, LDA rates increased to W48 (DAPSA, 44.4%; DAS28, 47.8%; PASDAS, 34.4%; GRACE, 33.3%; mCPDAI, 40.2%), and 27.0% and 64.0% achieved MDA and a PsARC response, respectively. In the placebo→guselkumab crossover group, W48 response rates were similar to the guselkumab-randomized group.<div class="boxTitle">Conclusion</div>Guselkumab treatment provided substantial benefits across multiple disease domains, with increasing proportions of patients achieving LDA/remission over 1 year, highlighting the effectiveness of guselkumab despite previous inadequate response to TNFi.</span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Objectives</div>Whilst biologic therapy is used for Behçet’s syndrome of all subtypes refractory to first-line immunomodulation, there has been an absence of high-quality evidence and no predictive biomarkers to optimally inform choice. BIO-BEHÇET’S was a randomized, controlled, head-to-head clinical trial comparing the two most frequently used biologics in active refractory Behçet’s.<div class="boxTitle">Methods</div>This was a Bayesian-designed, pragmatic, standard of care, two-arm, parallel head-to-head trial at four UK centres. Patients with active disease were randomized to infliximab or IFN-α2a, and received follow-up with symptom-directed examination at weeks 12 and 24. The primary outcome was the Behçet’s Disease Activity Index (BDAI) at 12 weeks. Secondary outcomes included BDAI at 24 weeks and significant improvement in individual organ systems, including ocular symptoms, oral and genital ulcers, arthritis pain, quality of life, disease activity and steroid use. Biomarkers were also investigated but are reported elsewhere.<div class="boxTitle">Results</div>Seventy-nine patients were recruited. Both treatments were equally effective, with a mean difference of 0.13 in BDAI (80% confidence interval: –0.19, 0.46). No significant differences were observed for secondary outcomes, though there were clinically significant within-group reductions for each over time. A modest steroid-sparing effect was observed, with complete cessation of steroids in 20% and 44% of those randomized to infliximab and IFN-α2a, respectively. There was a trend for minor benefit in favour of infliximab in terms of tolerability and persistence.<div class="boxTitle">Conclusion</div>In this first reported, high-quality, head-to-head trial of two biologics in Behçet’s, both infliximab and IFN-α2a showed comparable short-term clinical efficacy and safety in refractory active disease of all subtypes.<div class="boxTitle">Trial registration</div>EudraCT: 2014–005390-36; ISRCTN: ISRCTN49793874</span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Objective</div>OA is a joint disease linked with pathologic cartilage calcification, caused by the deposition of calcium-containing crystals by chondrocytes. Despite its clinical significance, the precise mechanisms driving calcification remain elusive. This study aimed to identify crucial players in cartilage calcification, offering insights for future targeted interventions against OA.<div class="boxTitle">Methods</div>Primary murine chondrocytes were stimulated with secondary calciprotein particles (CPP2) or left untreated (NT) for 6 h. Calcification was assessed by alizarin red staining. RNA was analysed by Bulk RNA sequencing. Differentially expressed (DE) genes were identified [cutoff: abs(LogFC)>1 and adjusted <span style="font-style:italic;">P</span>-value < 0.05], and top 50 DE genes were cross-referenced with human OA datasets from previous studies (i.e. healthy vs. OA cartilage, or undamaged vs. damaged cartilage). RNA from NT and CPP2-stimulated primary human OA chondrocytes were used to validate genes by qPCR.<div class="boxTitle">Results</div>CPP2 induced crystal formation by chondrocytes and significantly modulated 1466 genes. Out of the top 50 DE genes in CPP2, 27 were confirmed in published OA cartilage datasets. Of those genes, some are described in calcification and/or OA (<span style="font-style:italic;">Errfi1</span>, <span style="font-style:italic;">Ngf</span>, <span style="font-style:italic;">Inhba</span>, <span style="font-style:italic;">Col9a1</span>). Two additional ones (<span style="font-style:italic;">Rcan1</span>, <span style="font-style:italic;">Tnfrsf12a</span>) appear novel and interesting in the context of calcification and OA. We validated modulation of these six genes in calcifying human chondrocytes from five patients. Ultimately, we unveiled two distinct gene families modulated by CPP2: the first comprised cytoskeletal genes (<span style="font-style:italic;">Actb</span>, <span style="font-style:italic;">Tpm1</span>, <span style="font-style:italic;">Cfl1</span>, <span style="font-style:italic;">Tagln2</span>, <span style="font-style:italic;">Lmna</span>), while the second encompassed extracellular matrix genes (<span style="font-style:italic;">Fmod</span>, <span style="font-style:italic;">Sparc</span>, <span style="font-style:italic;">Col9a1</span>, <span style="font-style:italic;">Cnmd</span>).<div class="boxTitle">Conclusion</div>CPP2 modulates genes in chondrocytes that could represent new targets for therapeutic interventions in OA.</span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Objectives</div>Deucravacitinib is a novel, oral, selective, allosteric tyrosine kinase 2 (TYK2) inhibitor belonging to a distinct class of enzyme inhibitors. In a phase 2 trial in psoriatic arthritis (NCT03881059), deucravacitinib was significantly more efficacious than placebo across multiple endpoints, including achieving minimal disease activity (MDA). This <span style="font-style:italic;">post hoc</span> analysis further evaluated the achievement of individual components of the MDA criteria with deucravacitinib treatment and the time course of responses in the phase 2 trial.<div class="boxTitle">Methods</div>Patients (<span style="font-style:italic;">N</span> = 203) were randomized 1:1:1 to once daily treatment with placebo, deucravacitinib 6 mg or deucravacitinib 12 mg. The proportions of patients achieving MDA and each of the seven individual MDA components through week 16 were assessed.<div class="boxTitle">Results</div>At baseline, although some patients met criteria for individual MDA components, none of the patients met the composite MDA criterion, and all components were balanced overall across treatment arms. Treatment with deucravacitinib was associated with a numerically greater mean reduction from baseline in all MDA components <span style="font-style:italic;">vs</span> placebo over 16 weeks of treatment. At week 16, a greater percentage of patients treated with either dose of deucravacitinib <span style="font-style:italic;">vs</span> placebo achieved the threshold criteria for meeting MDA in each of the components.<div class="boxTitle">Conclusions</div>More patients treated with deucravacitinib met each of the MDA components <span style="font-style:italic;">vs</span> placebo, along with a higher rate of MDA response, after 16 weeks of treatment.</span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Objectives</div>This study focused on the prevalence and impact of ANA in aPL-positive patients without concomitant systemic autoimmune rheumatic diseases (SARDs).<div class="boxTitle">Methods</div>Data from aPL-positive patients with or without Revised Sapporo APS classification criteria were retrieved from the Antiphospholipid Syndrome Alliance for Clinical Trials and International Networking (APS ACTION) Registry. Patients with concomitant SARDs were excluded.<div class="boxTitle">Results</div>A total of 430 aPL-positive patients were included in the analysis, 56% ANA-positive (ANA+) and 44% ANA-negative (ANA−). ANA positivity was significantly associated with history of haematologic manifestations (persistent autoimmune haemolytic anaemia, thrombocytopenia, leukopenia and/or lymphopenia) (16% of ANA+ <span style="font-style:italic;">vs</span> 7% of ANA−, <span style="font-style:italic;">P = </span>0.006). Triple aPL-positivity was more frequent in the ANA+ subgroup (<span style="font-style:italic;">P = </span>0.02), along with low baseline C3 and C4 levels (<span style="font-style:italic;">P = </span>0.05 and <span style="font-style:italic;">P = </span>0.009, respectively), and higher frequency for ENA. Among aPL-positive patients with no APS classification, ANA+ patients showed a higher rate of arthritis (<span style="font-style:italic;">P = </span>0.006). Among female patients who have experienced at least one pregnancy, 113 were ANA+ and 96 were ANA−; ANA− patients had a higher number of pregnancies (<span style="font-style:italic;">P = </span>0.018), and number of live births (<span style="font-style:italic;">P = </span>0.014). A wider proportion of ANA+ patients were treated with HCQ (<span style="font-style:italic;">P </span><<span style="font-style:italic;"> </span>0.001).<div class="boxTitle">Conclusion</div>When we analysed aPL-positive patients with no other SARDs, ANA status was not associated with thrombosis or pregnancy morbidity. Interestingly, ANA+ patients showed higher rates of systemic autoimmune features, including haematologic manifestations, multiple aPL positivity, lower complement levels, ENA positivity, and joint involvement, and were more often treated with HCQ. Finally, aPL-positive subjects who were ANA− had a higher rate of pregnancies and live births.</span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Objectives</div>Eosinophilic granulomatosis with polyangiitis (EGPA) is frequently associated with refractory chronic rhinosinusitis with nasal polyps (CRSwNP), despite current treatments. Dupilumab demonstrated efficacy in the treatment of severe and uncontrolled CRSwNP, with improvements in patient-reported outcome measures (PROMs) and in objective measurements. This study aims to evaluate efficacy and safety of dupilumab in refractory CRSwNP in EGPA patients.<div class="boxTitle">Methods</div>A prospective observational study was conducted on EGPA patients treated with dupilumab between 2021 and 2023. Patients in a phase of prolonged remission of vasculitis manifestations but still experiencing active CRSwNP were included. Clinical, biological, and rhinologic evaluations were performed, alongside with PROMs and nasal cytology. Complete response was defined by BVAS = 0 and prednisone dose ≤4 mg/day, while partial response by BVAS = 0 and prednisone dose >4 mg/day.<div class="boxTitle">Results</div>Nine EGPA patients were included. After 3 months, 55.6% achieved complete response, increasing to 83.3% at 12 months. Nasal symptoms and patient-reported outcomes improved significantly, with sustained efficacy over 12 months. An improvement in quality of life was also observed, with a significant reduction in the AAV-PRO score. Nasal cytology revealed reductions in eosinophils and neutrophils counts. Adverse events occurred in 44.4%, including hypereosinophilia in two cases, which led to dupilumab discontinuation.<div class="boxTitle">Conclusion</div>Dupilumab is an effective treatment option for severe and refractory ENT manifestations in EGPA, as it improves symptoms, reduces inflammation, and leads to better a quality of life. However, careful patient selection and monitoring are necessary to minimize adverse events and optimize outcomes.</span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Objective</div>This study aimed to evaluate the density of tubulointerstitial macrophages with renal outcomes in patients with myeloperoxidase-anti-neutrophil cytoplasmic antibody associated glomerulonephritis (MPO-ANCA-associated GN).<div class="boxTitle">Methods</div>This study analysed patients with MPO-ANCA-associated GN who had renal biopsies at Jinling Hospital. It looked at the density of CD68+ macrophages in the tubulointerstitium and examined correlations with serum creatinine levels, urinary protein levels, treatment regimen and renal histologic class. The study used KM curves to show the impact of these factors on renal prognosis and conducted multivariate analyses with Cox proportional hazards regression models.<div class="boxTitle">Results</div>A total of 172 patients with MPO-ANCA-associated GN (median age: 50 y, 43.6% male) were included. Stratification of the cohort into tertiles was based on tubulointerstitial macrophage density. Significant differences in serum creatinine levels, induction treatment regimen, the rates of end-stage kidney disease, and renal histologic class were observed between the three groups. Correlation analysis showed that induction treatment regimen and renal histologic class were correlated with tubulointerstitial macrophage density. Kaplan–Meier curves illustrated patients with a lower presence of CD68+ macrophages in the tubulointerstitium experienced significantly better renal survival compared with those with a higher presence. The higher levels of CD68+ macrophage infiltration were significantly associated with adverse renal outcomes. This association persisted after adjusting for potential confounders including baseline serum creatinine, histopathological class, and induction therapy modalities.<div class="boxTitle">Conclusion</div>The results of our study provide insight into the prognostic significance of macrophage infiltration in the tubulointerstitium in MPO-ANCA-associated GN.</span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Objective</div>Upon commencement of therapy for active disease, patients with systemic lupus erythematosus (SLE) show varying evolution regarding disease activity measures and patient-reported outcomes (PROs). Our objective was to identify disease evolution trajectories to gain a deeper understanding of SLE progression, ultimately improving future trial design.<div class="boxTitle">Methods</div>Patients with ≥2 visits and available data on Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K), British Isles Lupus Assessment Group (BILAG), Physician Global Assessment (PGA), Functional Assessment of Chronic Illness Therapy—Fatigue (FACIT-F), and glucocorticoid use were included in a <span style="font-style:italic;">post hoc</span> analysis of four randomized controlled trials of belimumab (BLISS-52, BLISS-76, BLISS-SC, EMBRACE). Growth mixture modelling identified latent classes.<div class="boxTitle">Results</div>Among 2868 patients analysed, baseline median disease duration was 4.5 (interquartile range: 1.5–9.7) years and mean (±standard deviation) Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) Damage Index (SDI) 0.7 (±2.0), SLEDAI-2K 10.2 (±3.6), BILAG 17.0 (±7.8), PGA 1.5 (±0.5), FACIT-F 30.6 (±11.9) and prednisone dose 11.0 (±8.9) mg/day. In the initial model, glucocorticoid use and dose yielded high standard errors, indicating a weak link with the latent process. A refined model considered only clinical measures and FACIT-F, corrected for intervention and SDI; no other covariates improved the fit. Four classes best described disease evolution: highly active, responders; highly active, non-responders; moderately active, responders; moderately active, non-responders. Lupus Low Disease Activity State and Definitions of Remission in SLE remission attainment associated with latent classes.<div class="boxTitle">Conclusion</div>By linking disease activity measures with PROs, we identified four distinct trajectories describing SLE evolution following the initiation of therapy. This classification could be valuable for personalizing treatment and guiding biological studies aimed at distinguishing patients with varying anticipated treatment responses, as no single clinical variable alone can predict disease progression.</span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Objectives</div>To evaluate urinary activated leucocyte cell adhesion molecule (ALCAM) and CD6 as predictors of LN progression or disease resolution across a 1-year study.<div class="boxTitle">Methods</div>Serum and urine samples from biopsy proven LN subjects (<span style="font-style:italic;">n</span> = 122) were prospectively collected over the course of a year at 3- or 6-month intervals (weeks 0, 12, 26 and 52) across multiple study sites and assessed for soluble ALCAM and CD6 levels. Urine creatinine from the same urine sample was used to normalize the levels of urinary ALCAM and urinary CD6. Measured levels of serum and urine ALCAM and CD6 were then analysed against disease metrics cross-sectionally and longitudinally.<div class="boxTitle">Results</div>Cross-sectional analysis at baseline revealed that urinary ALCAM significantly correlated with urine protein creatinine ratio, renal SLEDAI, and the Physician Global Assessment (PGA), and negatively correlated with serum C3 and C4. Receiver operating characteristic curve analysis demonstrated that urinary ALCAM is a predictor of LN with an area under the curve (AUC) of 0.97, compared with urinary CD6 with an AUC of 0.71. Importantly, the change in urinary ALCAM over a 3-month period distinguished between non-responders and responders at week 52.<div class="boxTitle">Conclusion</div>Urinary ALCAM is reflective of changes in LN and may be predictive of response status.</span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Objectives</div>Referral of patients from dermatology to rheumatology practices due to psoriasis is unnecessary delayed. Many times musculoskeletal symptoms are the first reason for consultation. We aimed to estimate the proportion of ARP-PsA (arthralgia with risk to progression) defined by patients with arthralgia and the presence of psoriasis and/or a family history. Also, identify clinical, laboratory and imaging prognostic factors of PsA progression within the ARP-PsA group over a one year follow-up period.<div class="boxTitle">Methods</div>Patients were included in a comprehensive arthralgia evaluation program, with the ARP-PsA criteria defined as arthralgia with Pso and/or a family history of Pso, not referred from dermatology. Baseline characteristics were analysed, and the progression to PsA at one year was assessed. Multivariate analysis identified predictor features for progression.<div class="boxTitle">Results</div>Of the 1419 patients, 8.4% met ARP-PsA criteria, and 29% of this subgroup developed PsA at one year. Baseline differences between those who developed PsA and those who did not included family history, Pso duration, pain severity, joint count and imaging findings (X-ray and ultrasound). Multivariate analysis revealed the predictive significance of a combination of Pso plus family history of psoriasis disease, synovitis by Power Doppler ultrasound, ultrasound enthesopathy findings and low tender joint count.<div class="boxTitle">Conclusion</div>The frequency of patients ARP-PsA was 8.4%, of whom 29% developed PsA at one year. The main predictor variables for this progression were identified.</span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Objective</div>Identification of those at high and low risk of disease relapse is a major unmet need in the management of patients with ANCA-associated vasculitis (AAV). Precise stratification would allow tailoring of immunosuppressive medication. We profiled the autoantibody repertoire of AAV patients in remission to identify novel autoantibodies associated with relapse risk.<div class="boxTitle">Methods</div>Plasma samples collected from 246 AAV patients in remission were screened for novel autoantibodies using in-house generated protein arrays including 42 000 protein fragments representing 18 000 unique human proteins. Patients were categorized based on the occurrence and frequency of relapses. We modelled the association between these antibodies and relapse occurrence using descriptive and high dimensional regression approaches.<div class="boxTitle">Results</div>We observed nine autoantibodies at higher frequency in samples from AAV patients experiencing multiple relapses compared with patients in long-term remission off therapy. LASSO analysis identified six autoantibodies that exhibited an association with relapse occurrence after sample collection. Antibodies targeting homeostatic iron regulator (HFE) and synaptotagmin 5 (SYT5) were identified as associated with relapse in both analyses.<div class="boxTitle">Conclusion</div>Through a broad protein array-based autoantibody screening, we identified two novel autoantibodies directed against HFE and SYT5 as candidate biomarkers of relapse in AAV.</span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Objectives</div>The aim of this study was to validate the Patient self-Assessment of Skin Thickness in Upper Limb (PASTUL) questionnaire in SSc and assess impact of skin involvement on health-related quality of life (HRQoL).<div class="boxTitle">Methods</div>Participants were included in four UK centres. PASTUL specifies a grading of skin at eight sites corresponding to the modified Rodnan Skin Score (mRSS). Construct validity was assessed by comparing PASTUL scores with mRSS. HRQoL was evaluated with EuroQoL 5 dimension 5 levels (EQ5D5L) and Leeds SSc QoL questionnaires. Additionally, correlation between PASTUL and Scleroderma Skin Patient-Reported Outcome (SSPRO) was explored. Follow-up was 12 months.<div class="boxTitle">Results</div>In total, 196 participants were included, mean age was 56.4 years (<span style="text-transform:lowercase;font-variant:small-caps;">s</span>.<span style="text-transform:lowercase;font-variant:small-caps;">d</span>. 13.9), 80.6% female (<span style="font-style:italic;">n</span> = 158), mean disease duration 11.9 years (<span style="text-transform:lowercase;font-variant:small-caps;">s</span>.<span style="text-transform:lowercase;font-variant:small-caps;">d</span>. 9.9), 110 (56.1%) had lcSSc and 81 (41.3%) dcSSc. PASTUL and upper limb mRSS were well correlated at baseline, 6 and 12 months [intraclass correlation coefficients (ICC) = 0.67, 0.78 and 0.62, <span style="font-style:italic;">P</span> < 0.001]. Test–retest reliability was good (ICC = 0.83, <span style="font-style:italic;">P</span> < 0.001). There was a stronger correlation between PASTUL and upper limb mRSS in dcSSc compared with lcSSc (0.69 <span style="font-style:italic;">vs</span> 0.51, <span style="font-style:italic;">P</span> < 0.001). In participants with early disease (<4 years) PASTUL was moderately correlated with HRQoL (r = 0.53, <span style="font-style:italic;">P</span> < 0.001); correlations were weaker in the whole group. Mean time to do the PASTUL self-assessment was 5.0 min (<span style="text-transform:lowercase;font-variant:small-caps;">s</span>.<span style="text-transform:lowercase;font-variant:small-caps;">d</span>. 3.7).<div class="boxTitle">Conclusion</div>PASTUL is a feasible outcome tool that adds to assessments such as SSPRO. Skin thickening is correlated with HRQoL, particularly in early disease.</span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Objective</div>Inflammation in patients with myositis would increase diffusion of water molecules across sarcolemma that could be detected with the help of diffusion tensor imaging (DTI). We aimed to determine an association between DTI of vastus lateralis (VL) and histopathological findings in cases of myositis and to estimate diagnostic performance of different MRI variables in predicting histopathological outcomes.<div class="boxTitle">Methods</div>This prospective cross-sectional observational study included 43 patients with myositis. MRI of bilateral thighs with DWI/DTI protocol was performed in all the patients. Thirty-three patients further underwent biopsy of right VL muscle. Imaging analysis included grading of ‘muscle oedema’ based on signal intensity (SI) and extent and ‘fatty infiltration’ based on extent on conventional sequences and, acquiring DWI and DTI parameters. Gold standard method to determine inflammation in muscles was histopathological examination. Comparison of DTI/DWI variables with clinical and histopathological variables was done.<div class="boxTitle">Results</div>The average DWI apparent diffusion coefficient (ADC) and DTI ADC values in the patients were 1.77 ± 0.35 and 2.06 ± 0.35, respectively. The average functional anisotropy (FA) was 0.39 ± 0.17 and, the three eigenvalues in the patients were 2.96 ± 0.63, 2.05 ± 0.32 and 1.20 ± 0.39, respectively. VL oedema SI weighted score was the best parameter for predicting effaced fascicular architecture and marked lymphocytic inflammation in endomysium on histopathology. VL fatty infiltration weighted score was the best parameter in predicting perifascicular atrophy.<div class="boxTitle">Conclusion</div>Addition of DWI or DTI did not add significantly in determining active inflammation in cases of myositis.</span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Objective</div>The association between colchicine use and the primary prevention of atherosclerotic cardiovascular disease (ASCVD) remains unknown. This study aimed to explore the association between colchicine use and new development of ASCVD and ASCVD-related mortality in patients with incident gout.<div class="boxTitle">Methods</div>This nested case–control study utilized the nationwide claims database of the Korean National Health Insurance System. Patients without a history of ASCVD who developed incident gout and were newly started on allopurinol as first-line therapy between 2011 and 2016 were initially screened. Individuals who experienced ASCVD event or ASCVD-related mortality during the follow-up period were matched with four controls for age, sex, income, residential area, co-morbidities and medications. The main exposure was colchicine use, assessed by (i) the cumulative defined daily doses (cDDDs) and (ii) the cumulative duration. For secondary analyses, the risk of ASCVD events and ASCVD-related mortality were examined separately.<div class="boxTitle">Results</div>Overall, 9346 patients with ASCVD event or ASCVD-related mortality were matched with 35 070 controls. The patient population was predominantly male. Compared with non-users, a curvilinear relationship between higher cDDDs of colchicine and the odds of ASCVD event was observed; the odds ratios (95% CI) were 1.09 (1.04, 1.15) for <90 cDDDs, 1.20 (1.07, 1.33) for 80–179 cDDDs and 1.21 (1.09, 1.35) for ≥180 cDDDs. This association was similarly observed for ASCVD events and ASCVD-related mortality.<div class="boxTitle">Conclusion</div>Colchicine use was associated with an increased risk of ASCVD in patients with newly diagnosed gout who did not have a prior history of ASCVD.</span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Objectives</div>To investigate bone mineral density (BMD), osteoporosis prevalence and SSc-specific associations of BMD in SSc patients compared with background population.<div class="boxTitle">Methods</div>In total, 211 SSc patients (182 women, 29 men; mean age 61.3 and 62.2 years, respectively) and 505 age- and sex-matched controls from the same geographic area participated. BMD and T-score at total hip and lumbar spine was measured by dual-energy X-ray absorptiometry. Osteopenia was defined as T-score –1.0 to –2.5, and osteoporosis as T-score ≤–2.5. Associates of low BMD were identified by multiple regression analysis.<div class="boxTitle">Results</div>Women with SSc had lower BMD for total hip (<span style="font-style:italic;">P</span> < 0.001) and spine (<span style="font-style:italic;">P</span> = 0.011), equivalent to ΔT-score –0.56 and –0.35 compared with controls. Osteopenia was present in 51.6% and 16.5% had osteoporosis (<span style="font-style:italic;">P</span> = 0.001, compared with controls). Already in women below age 45 years, differences in hip BMD were apparent (ΔT-score –0.93, <span style="font-style:italic;">P</span> = 0.005). In addition to expected risk factors for osteoporosis (older age, lower BMI and menopause), finger ulcers (<span style="font-style:italic;">P</span> = 0.009) and diffuse skin involvement (<span style="font-style:italic;">P</span> = 0.027) were associated with lower hip BMD in women. In men with SSc, more than half displayed osteopenia or osteoporosis and had numerically lower hip BMD than their age-matched counterparts.<div class="boxTitle">Conclusion</div>SSc patients, including men and younger women, have lower BMD than the background population. Finger ulcers and diffuse skin involvement, in addition to older age, lower BMI and being post-menopausal, are associated with lower BMD in women. The data emphasize the importance of performing bone health assessment of all SSc patients, including men and young subjects.</span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Objective</div>To determine serum type I IFN (IFN-α2a) concentrations in SSc patients, explore its association with cytokine/chemokine expressions and evaluate correlation with the phenotype including the predictive value for interstitial lung disease (ILD) progression.<div class="boxTitle">Methods</div>Serum samples were obtained from 200 SSc patients and 29 healthy controls. IFN-α2a levels were measured by ultrasensitive electrochemiluminescence assay. Pro-inflammatory and chemokine panels were determined by Luminex<sup>®</sup> Discovery Assay multiplex kit. Baseline SSc disease characteristics were recorded together with longitudinal data for determining ILD progression after 2 years.<div class="boxTitle">Results</div>IFN-α2a concentrations were higher in SSc patients compared with controls, although not reaching significance [means ± SD of 49.20 ± 156.8 fg/ml <span style="font-style:italic;">vs</span> 9.606 ± 4.399 fg/ml, respectively (<span style="font-style:italic;">P</span> = 0.158)]. Using the cut-off of 15.9 fg/ml, we identified 62 patients as having a type 1 (T1) IFN signature in their circulation. Patients with an IFN signature had significantly higher levels of chemokines (CCL8, CCL19, CXCL10, CXCL11) and the cytokine IL-1α compared with those without an IFN signature. IFN-α2a concentrations strongly correlated with a T1 IFN-related chemokine score supporting activation of this pathway. Phenotyping association queries revealed association between IFN values and both skin and ILD involvements at baseline. Longitudinal data did not identify IFN as a predictive marker for ILD progression.<div class="boxTitle">Conclusion</div>Using serum determinations, the activation of the T1 IFN pathway showed strong correlations with inflammatory mediators and associations with clinical manifestations, especially skin fibrosis and ILD in SSc patients. However, activated IFN pathway was not predictive of ILD progression.</span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Objectives</div>Glucagon-like peptide-1 receptor agonists (GLP1-RA) are an emerging class of medications with demonstrated promise in improving cardiometabolic outcomes. Whether these drugs may be useful in mitigating the cardiac risk associated with SLE remains unknown, and a recent case of drug-induced lupus secondary to GLP1-RA use calls the safety of GLP1-RAs in SLE patients into question. Accordingly, this retrospective analysis was initiated to evaluate outcomes of GLP1-RAs in SLE.<div class="boxTitle">Methods</div>All patients in the NYU Lupus Cohort who had used a GLP1-RA were eligible for inclusion. Patient characteristics were assessed at baseline (most recent rheumatology visit prior to starting GLP1-RA), 1–4 months and 6–10 months after GLP1-RA initiation.<div class="boxTitle">Results</div>Of the 1211 patients in the cohort, only 24 had received a GLP1-RA. Six were excluded due to insufficient documentation regarding duration of medication use. Of the remaining 18 (median age 50), 17 (94%) were female and nine (50%) were White. There was one mild-to-moderate flare at 6–10 months, but no patients accumulated new SLE criteria during the follow-up period. Compared with baseline, median BMI was reduced by 3% at 1–4 months (<span style="font-style:italic;">P</span> = 0.002) and 13% at 6–10 months (<span style="font-style:italic;">P</span> = 0.001). Nine (50%) patients were initially denied insurance coverage for a GLP1-RA.<div class="boxTitle">Conclusion</div>While limited by a small sample size, this descriptive study showed that GLP1-RAs did not trigger flares above expected background rates and were associated with significantly decreased BMI. Future studies exploring the potential benefits of GLP1-RAs in patients with SLE are warranted.</span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Objectives</div>SSc is an autoimmune connective tissue disease involving multiple organs. The most common clinical symptom of SSc is progressive fibrosis of the skin, and the pathologically manifestations of skin were activation and proliferation of fibroblasts and continuous proliferation of extracellular matrix. TGF-β can promote the proliferation and activation of fibroblasts, causing excessive deposition of collagen and structural proteins. Therefore, exploring the specific mechanism of TGF-β-related pathway on fibrosis is of great significance for improving skin fibrosis in SSc.<div class="boxTitle">Methods</div>Genes related to TGF-β pathway were screened through bioinformatics analysis, and SSc phenotypes were verified <span style="font-style:italic;">in vivo</span> and <span style="font-style:italic;">in vitro</span>. The relevant molecular mechanisms were preliminarily discussed in combination with transcriptome sequencing.<div class="boxTitle">Results</div>Human cysteine-rich secreted protein LCCL domain protein 2 (CRISPLD2) was found increased reactivity in TGF-β-induced fibroblasts, and the expression of ACTA2 (ɑ-SMA) decreased significantly in TGF-β-mediated fibroblasts with up-regulation of CRISPLD2.<div class="boxTitle">Conclusion</div>CRISPLD2 was found to have increased reactivity in TGF-β-induced fibroblasts, and we further confirmed that CRISPLD2 can participate in TGF-β-induced fibroblast fibrosis from multiple perspectives and levels in negative feedback regulation, and investigated the mechanism of CRISPLD2 in fibrosis.</span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Objective</div>The small bowel is affected in up to 50% of systemic sclerosis (SSc) patients, and some patients experience severe complications. Our aim was to use specific statistical methods to compare demographic and clinical features of SSc patients with and without abnormal small bowel to better characterize patients at risk for this complication.<div class="boxTitle">Methods</div>SSc patients with gastrointestinal symptoms were prospectively enrolled and underwent a scintigraphy-based whole gut transit (WGT) study. A cross-sectional analysis was performed comparing clinical features between patients with and without abnormal small bowel transit by WGT. Univariate logistic regression models and multivariable models were used to examine the relationship between clinical features and abnormal small bowel transit.<div class="boxTitle">Results</div>Of 130 patients enrolled in this study, 22 had abnormal small bowel transit. SSc patients with abnormal small bowel transit were more likely to be male [odds ratio (OR) = 3.70; 95% CI: 1.07, 12.50; <span style="font-style:italic;">P</span> = 0.038] and have more severe cardiac involvement (OR = 3.98; 95% CI: 1.10, 14.38; <span style="font-style:italic;">P</span> <span style="font-style:italic;">=</span> 0.035), while they were less likely to have sicca symptoms (OR = 0.30; 95% CI: 0.10, 0.94; <span style="font-style:italic;">P = </span>0.039). In multivariable analyses, sicca symptoms (OR = 0.28; 95% CI: 0.08, 0.96; <span style="font-style:italic;">P</span> <span style="font-style:italic;">=</span> 0.043) remained negatively associated with abnormal small bowel transit. Additionally, SSc patients with abnormal small bowel transit had higher mortality than patients with normal small bowel transit [hazard ratio (HR) = 4.57; 95% CI: 1.58, 13.24; <span style="font-style:italic;">P</span> <span style="font-style:italic;">=</span> 0.005].<div class="boxTitle">Conclusions</div>These findings suggest that patients with abnormal small bowel transit in SSc are more likely to be male, have more severe cardiac involvement, higher mortality and fewer sicca symptoms. Recognizing this patient subgroup is essential for risk stratification and optimizing clinical care.</span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Objectives</div>Uveitis is a common extra-musculoskeletal manifestation in SpA. The aim of this study was to analyze the prevalence of uveitis in SpA patients, and its association with geographical areas, and to determine whether its incidence differed between before and after the biologics era.<div class="boxTitle">Methods</div>ASAS-COMOSPA is a retrospective study that includes patients fulfilling Assessment in SpondyloArthritis International Society (ASAS) SpA classification criteria from 22 countries. The overall prevalence of uveitis was calculated, and factors associated with the onset of a first episode of uveitis were evaluated using a Cox regression. A Log-Rank test was performed to compare the new onset of uveitis in the non-biologics era (SpA onset before 2000) <span style="font-style:italic;">vs</span> biologics era (SpA onset after 2000).<div class="boxTitle">Results</div>A total of 3984 patients were included. The likelihood of presenting a first uveitis episode increased over time, from a prevalence of 10.5% (95% CI 9.5–11.4%) at the time of the SpA diagnosis to 46.6% (41.6–51.5%) after 30 years since the SpA diagnosis. HLA-B27 positivity, family history of uveitis, peripheral enthesitis, and IBD were associated with higher risk of uveitis. Patients with SpA disease onset after the year 2000 showed a lower prevalence of uveitis compared with those with disease onset before the year 2000 (8.2% <span style="font-style:italic;">vs</span> 25.5%, <span style="font-style:italic;">P</span> <0.01), as well as a lower incidence (2.8 per 100 person-years <span style="font-style:italic;">vs</span> 6.1 per 100 person-years, respectively).<div class="boxTitle">Conclusion</div>In our study, the risk of having suffered from at least one episode of uveitis ranged from 10% at the time of the diagnosis of axial SpA to 47% after 30 years of disease duration. Patients with disease onset after biologic therapy introduction showed a significantly lower prevalence and incidence of first episodes of uveitis.</span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Objectives</div>EBV is a widespread virus implicated in various diseases, including SLE. However, the specific genes and pathways altered in SLE patients with EBV infection remain unclear. We aimed to identify key genes and immune cells in SLE patients with EBV infection.<div class="boxTitle">Methods</div>The datasets of SLE (GSE50772 and GSE81622) and EBV infection (GSE85599 and GSE45918) were obtained from the Gene Expression Omnibus (GEO) database. Next, differential gene expression (DEGs) analyses were conducted to identify overlapping DEGs, and then enrichment analysis was performed. Machine learning was applied to identify key genes. Validation was conducted using receiver operating characteristic (ROC) curve analysis and expression level verification in test datasets and single-cell RNA sequencing. Immune cell infiltration patterns were analysed using CIBERSORTx, and clinical data were reviewed for SLE patients.<div class="boxTitle">Results</div>We identified 58 overlapping DEGs enriched in IFN-related pathways. Five overlapping DEGs (<span style="font-style:italic;">IFI27</span>, <span style="font-style:italic;">TXK</span>, <span style="font-style:italic;">RAPGEF6</span>, <span style="font-style:italic;">PIK3IP1</span> and <span style="font-style:italic;">PSENEN</span>) were selected as key genes by machine-learning algorithms, with <span style="font-style:italic;">IFI27</span> showing the highest diagnostic performance. The expression level of <span style="font-style:italic;">IFI27</span> was found to be higher in CD4 CTL, CD8-naïve and various B cell subsets of SLE patients with EBV infection. I<span style="font-style:italic;">FI27</span> showed significant correlation with B intermediate and CD4 CTL cells. Clinical data showed lower CD4 T cell proportions in SLE patients with EBV infection.<div class="boxTitle">Conclusion</div>This study identified <span style="font-style:italic;">IFI27</span> as a key gene for SLE patients with EBV infection, influencing CD4 CTL and B cell subtypes. These findings enhance the understanding of the molecular mechanisms linking SLE and EBV infection, providing potential targets for diagnostic and therapeutic strategies.</span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Objectives</div>To examine the clinical impact of a fast-track PMR clinic to enable early diagnosis and treatment, and to define both patient and disease characteristics in newly diagnosed PMR.<div class="boxTitle">Methods</div>Primary care physicians were invited to refer patients with new PMR to our fast-track clinic. Referral criteria included new onset shoulder or pelvic girdle pain and/or stiffness with elevated inflammatory markers in patients over 50 years. All patients were seen within 72 h of referral. Patients with a rheumatology diagnosis of PMR had an US of their temporal and axillary arteries.<div class="boxTitle">Results</div>172 patients were referred from primary care over 12 months. 39% of patients referred with suspected PMR had an alternative diagnosis for which PMR regimen glucocorticoids was inappropriate. 55% of the non-PMR diagnoses were other inflammatory rheumatological conditions requiring follow-up. Only 20% of patients referred from primary care already on glucocorticoids were commenced on bone protection. PMR patients were comorbid, with a mean of 2.5 other conditions. 75% of PMR patients experienced a glucocorticoid-related adverse event in the first 12 months of treatment. 17% of patients with new PMR had US features of subclinical GCA.<div class="boxTitle">Conclusion</div>The commencement of glucocorticoid therapy should be deferred until after specialist evaluation to enable an accurate clinical diagnosis. A delay in treatment can only realistically be avoided if general practitioners have access to a fast-track PMR clinic. We believe that rheumatologists should consider establishing fast-track PMR clinics and this study provides a strong case for and a template to support this practice innovation.</span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Objectives</div>There are an increasing number of centres performing research on high-resolution vessel wall magnetic resonance imaging (VW-MRI) in GCA. However, harmonized approaches to VW-MRI in GCA are lacking and are essential to performing multicentre studies. Using a data-driven, consensus-based approach, an international expert group developed a standardized MRI protocol and scoring system to advance multi-centred research in cranial GCA.<div class="boxTitle">Methods</div>A targeted literature review of VW-MRI in cranial GCA was conducted. A working group comprised of radiologists, rheumatologists and ophthalmologists with expertise in VW-MRI and GCA reviewed the results of the literature search, presented relevant data and images from their respective centres, and then reached consensus on recommendations related to key MRI structures, MRI sequences, scoring system and other important considerations.<div class="boxTitle">Results</div>A total of 21 relevant articles were identified and reviewed. Based on published literature, structures to be evaluated on MRI were categorized based on anatomic location (extradural cranial, intradural cranial and orbits) and prioritization (core vs elective). Essential and elective sequences to comprehensively image cranial and orbital structures while minimizing scan time were determined along with scoring systems to grade contrast enhancement.<div class="boxTitle">Conclusion</div>This report describes a standardized approach to facilitate research of VW-MRI in cranial GCA that is the result of a multidisciplinary, international collaboration of experts in VW-MRI and/or GCA.</span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Objectives</div>Mycophenolate mofetil (MMF) is an immunosuppressant used to treat rheumatological diseases, including systemic sclerosis (SSc). While MMF is an established inhibitor of lymphocyte proliferation, recent evidence suggests MMF also mediates effects on other cell types. The goal of this study was to determine the effect of MMF on monocytes and macrophages, which have been implicated in SSc pathogenesis.<div class="boxTitle">Methods</div>Human monocyte–derived macrophages were cultured with the active MMF metabolite, mycophenolic acid (MPA), and assessed for changes in viability and immuno-phenotype. Guanosine supplementation studies were performed to determine whether MPA-mediated effects were dependent on <span style="font-style:italic;">de novo</span> purine synthesis. The ability of MPA-treated macrophages to induce fibroblast activation was evaluated, and dermal myeloid expression signatures were analysed in MMF-treated SSc patients.<div class="boxTitle">Results</div>MPA reduced viability and induced apoptosis in monocytes and macrophages at doses (average IC50 = 1.15 µg/ml) within the target serum concentration of MMF-treated SSc patients (1–3 µg/ml). These effects were reversed by guanosine supplementation. Low-dose MPA (0.5 µg/ml) attenuated IL-4 or SSc plasma-mediated macrophage activation, and inhibited the ability of SSc plasma-activated macrophages to induce SSc fibroblast activation. Gene expression studies demonstrated significant reductions in dermal myeloid signatures in MMF-responsive SSc patients.<div class="boxTitle">Conclusion</div>For the first time, we have demonstrated that MMF inhibits the viability and pro-fibrotic activation of human monocytes and macrophages, which is dependent on <span style="font-style:italic;">de novo</span> purine synthesis. Coupled with myeloid gene expression attenuation following MMF treatment in patients, these results suggest that the fibrotic inhibition observed with MMF may be attributable, at least in part, to direct effects on myeloid cells.</span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Objectives</div>Patients with autonomic dysfunction, or dysautonomia, often report discolouration of their dependent extremities, which is thought to be from venous pooling or acrocyanosis. A subset of patients with SSc are affected by dysautonomia but may be challenging to identify. We sought to determine whether patients with SSc who report discolouration in their feet have a higher burden of autonomic symptoms, including orthostatic, gastrointestinal (GI), urinary, secretomotor and pupillomotor.<div class="boxTitle">Methods</div>167 patients with SSc completed the Composite Autonomic Symptom Score (COMPASS)-31 survey, which queries whether the patient experiences discolouration of the feet or hands. We compared the COMPASS-31 subdomain scores between SSc patients with and without foot discolouration. Seventy-nine patients with postural orthostatic tachycardia syndrome (POTS) also completed the COMPASS-31 questionnaire for comparison.<div class="boxTitle">Results</div>We found that extremity discolouration is common in POTS and more often affects the feet, whereas in SSc, the hands are more frequently involved; 62% of SSc patients report colour changes in their feet. These patients are more likely to have other autonomic symptoms, including orthostatic (11.7 ± 10.6 <span style="font-style:italic;">vs</span> 8.6 ± 9.9, <span style="font-style:italic;">P</span> = 0.06), GI (11.3 ± 4.3 <span style="font-style:italic;">vs</span> 8.8 ± 4.3, <span style="font-style:italic;">P</span> = 0.0003), urinary (1.4 ± 1.5 <span style="font-style:italic;">vs</span> 0.8 ± 1.3, <span style="font-style:italic;">P</span> = 0.002) and secretomotor (7.0 ± 3.8 <span style="font-style:italic;">vs</span> 5.9 ± 3.8, <span style="font-style:italic;">P</span> = 0.06) symptoms. These associations persist in a multivariable model after adjusting for potential confounders.<div class="boxTitle">Conclusion</div>Dependent extremity discolouration is common in dysautonomia. Patients with SSc who report colour changes in their feet are more likely to report other symptoms of autonomic dysfunction.</span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Objectives</div>Gut and joint disease commonly co-occur in SpA. Up to 50% of patients with SpA show signs of subclinical gut inflammation, of which 10% develops IBD. However, the mechanisms underlying this gut–joint axis are still unclear. Here we investigated the hypothesis that restricted expression of a pro-inflammatory cytokine in the intestine may trigger the onset of combined gut and joint inflammation.<div class="boxTitle">Methods</div>Intestinal expression of human TNF (hTNF) was achieved by driving <span style="font-style:italic;">hTNF</span> gene expression using the rat FAPB2 promoter, creating a new animal model, TNF<sup>gut</sup> mice, that expresses hTNF in the proximal intestinal tract. Intestinal-specific TNF<sup>gut</sup> mice were examined for pathological changes in the intestine and extra-intestinal tissues by means of histology, reverse transcription PCR (RT-PCR) and flow cytometry, along with 16S sequencing on stools.<div class="boxTitle">Results</div>Local expression of hTNF in the epithelium of the small intestine induces a pro-inflammatory state of the proximal intestinal tract, with epithelial alterations and induction of members of the S100 family, as well as local upregulation of Th17 and Treg, but no obvious signs of dysbiosis. Curiously, TNF<sup>gut</sup> mice develop sacroiliitis (<span style="font-style:italic;">P</span> <0.05) in addition to small bowel inflammation (<span style="font-style:italic;">P</span> <0.05). However, no signs of peripheral arthritis or enthesitis could be documented.<div class="boxTitle">Conclusion</div>Intestinal expression of hTNF is sufficient to initiate a pro-inflammatory cascade culminating in small bowel inflammation and sacroiliitis. Thus, gut-derived cytokines are sufficient to induce SpA.</span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Objective</div>Interstitial fibrosis and tubular atrophy (IFTA) were frequent histologic features of LN, and LN patients with IFTA have poor renal outcomes. In this study, we aimed to construct prediction models for the IFTA in LN patients.<div class="boxTitle">Methods</div>This retrospective study included 303 patients with biopsy-proven LN at the Affiliated Hospital of Qingdao University and Fujian Medical University Union Hospital. The participants were randomly divided into development and validation cohorts. They were further divided into IFTA and non-IFTA groups. The least absolute shrinkage and selection operator (LASSO) regression model with laboratory test results collected at the time of kidney biopsy was used to optimize feature selection for the risk model. Multivariable logistic regression analysis was applied to build a predicting model incorporating the feature selected in the LASSO regression model. Discrimination, calibration, and clinical usefulness of the predicting model were assessed using the C-index, calibration plot, and receiver operating characteristic curve analysis. Internal validation was assessed using the bootstrapping validation. A nomogram for individual assessment was constructed based on the preferable model.<div class="boxTitle">Results</div>Predictors contained in the prediction nomogram included age, BMI, mean arterial pressure, log antinuclear antibody (logANA), C3, estimated glomerular filtration rate and serum uric acid. The model displayed good discrimination with a C-index of 0.794 (95% CI 0.734–0.854) and good calibration. High C-index value of 0.857 (95% CI 0.776–0.938) could still be reached in the interval validation. A nomogram model based on the LASSO model was created for producing a probability score of IFTA in LN patients.<div class="boxTitle">Conclusion</div>With excellent predictive abilities, the nomogram may provide a simple and reliable tool to distinguish LN patients with IFTA and help physicians make clinical decisions in their comprehensive assessment.</span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Objectives</div>Current data on arterial and venous thrombotic events (ATE and VTE) and cardiovascular (CV) risk management in the European systemic lupus erythematosus (SLE) population are limited. This study aimed to investigate the incidence and risk of thrombotic events and all-cause death in an Italian SLE cohort over the past decade, along with its pharmacotherapy.<div class="boxTitle">Methods</div>Incident SLE cases between 2010 and 2019 were identified using administrative health databases of the Lombardy Region. The association between SLE and outcomes, compared with age- and sex-matched controls, was reported as incidence rate per 1000 person-years (PY) and as adjusted hazard ratios (HR) with 95% confidence intervals.<div class="boxTitle">Results</div>Overall, 2133 SLE patients and 21 283 no-SLE individuals were included. A higher incidence rate of ATE (4.22 <span style="font-style:italic;">vs</span> 2.26 per 1000 PY), VTE (1.85 <span style="font-style:italic;">vs</span> 0.67 per 1000 PY) and all-cause death (15.18 <span style="font-style:italic;">vs</span> 6.22 per 1000 PY) was reported in SLE patients than in those without (<span style="font-style:italic;">P</span> < 0.0001) as well as an increased risk of ATE (HR, 1.65; 95% CI: 1.20, 2.26), VTE (HR, 2.25; 95% CI: 1.35, 3.74) and all-cause death (HR, 1.81; 95% CI: 1.52, 2.15). After SLE diagnoses, hydroxychloroquine and glucocorticoids were prescribed for at least 60% of patients. Additionally, a higher exposure to cardiovascular medications was also seen in SLE patients.<div class="boxTitle">Conclusion</div>Our findings confirmed higher risks of ATE, VTE and all-cause death in SLE patients. While increased CV medication use after SLE diagnoses suggests heightened awareness to CV risk profile, more attention is required to balance SLE disease activity with minimizing exposure to drugs associated with exacerbating CV risk.</span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Objective</div>The objective of this study was to investigate the inter-relationships among genetic risk, adherence to a healthy lifestyle, and susceptibility to hyperuricaemia.<div class="boxTitle">Methods</div>This prospective cohort study was conducted with 7241 hyperuricaemia-free individuals aged ≥20 years from the Tohoku Medical Megabank Community–based cohort study. A comprehensive lifestyle score included assessment of BMI, smoking, drinking, and physical activity, and a polygenic risk score (PRS) was constructed based on uric acid loci from a previous genome-wide association study meta-analysis. A multiple logistic regression model was used to estimate the association between genetic risk, adherence to a healthy lifestyle, and hyperuricaemia incidence and to calculate the area under the receiver operating characteristic curve (AUROC). Hyperuricaemia was defined as a uric acid level of ≥7.0 mg/dL or a self-reported history of hyperuricaemia.<div class="boxTitle">Results</div>Of the 7241 adults [80.7% females; mean (±<span style="text-transform:lowercase;font-variant:small-caps;">s</span>.<span style="text-transform:lowercase;font-variant:small-caps;">d</span>.) age: 57.7 (12.6) years], 217 (3.0%) developed hyperuricaemia during 3.5 years of follow-up period. Genetic risk was correlated with hyperuricaemia development (<span style="font-style:italic;">P</span> for interaction = 0.287), and lifestyle risks were independently associated. Participants with a high genetic risk and poor lifestyle had the highest risk (odds ratio: 5.34; 95% CI: 2.61–12.10). Although not statistically significant, adding the PRS in the model with lifestyle information improved predictive ability (AUROC = 0.771, 95% CI: 0.736–0.806 for lifestyle; AUROC = 0.785, 95% CI: 0.751–0.819 for lifestyle and PRS; <span style="font-style:italic;">P=</span> 0.07).<div class="boxTitle">Conclusion</div>A healthy lifestyle to prevent hyperuricaemia, irrespective of genetic risk, may mitigate the genetic risk. Genetic risk may complement lifestyle factors in identifying individuals at a heightened hyperuricaemia risk.</span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Objectives</div>We present the first case of a Majeed syndrome in a girl of central-European ancestry.<div class="boxTitle">Methods</div>Patient’s medical records were reviewed. A next-generation sequencing (NGS) panel for autoinflammatory diseases was performed and the mutation was confirmed by Sanger analysis. Freshly isolated monocytes were activated with lipopolysaccharide ± ATP. The concentration of inflammatory cytokines was assessed in monocyte supernatants.<div class="boxTitle">Results</div>A 2-year-old girl presented with pain in the lower limbs, increase of acute phase reactants and persistent microcytic anaemia. The MRI showed bilateral short time inversion recovery (STIR) hyper-intensity of the spongy osseous tissue of the femur, tibia, radius, ulna and astragalus. Bone marrow analysis revealed increased trilinear cellularity with signs of dyserythropoietic anaemia. The NGS panel detected the presence of two novel compound heterozygous mutations in the <span style="font-style:italic;">LPIN2</span> gene, confirmed by Sanger analysis. Treatment with anakinra was started with a prompt resolution of the clinical picture. Increased kinetics and concentration of IL-1β were observed in the patient’s monocytes compared with healthy controls, with a marked drop following the start of therapy. About 6 months after the start of the therapy, resolution of MRI findings, microcytic anaemia and dyserythropoiesis at bone marrow aspirate were observed.<div class="boxTitle">Conclusion</div>We describe the first case of Majeed syndrome in a patient of central-European ancestry. The functional test on circulating monocytes before and after therapy with anakinra confirmed pathogenicity of the mutation and the role of LPIN2 in the NLRP3 inflammasome activation. Anti-IL1 agents were effective, leading not only to the resolution of bone lesions but also to an improvement of dyserythropoiesis.</span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Objective</div>Bacterial translocation across the gut barrier has been implicated in the pathogenesis of SLE, though the underlying mechanisms remain unclear. This study aimed to investigate the role of translocated bacteria in the context of molecular mimicry by utilizing lupus model mice and blood samples from untreated SLE patients.<div class="boxTitle">Methods</div>Bacterial translocation was evaluated using nonselective cultured mesenteric lymph nodes (MLNs) from B6SKG mice, a lupus model characterized by impaired TCR signalling and gut dysbiosis. The relationships of detected pathobionts with autoantibody production were examined using <span style="font-style:italic;">in vivo</span> experiments, ELISA, immunoblotting and epitope mapping.<div class="boxTitle">Results</div>Culture-based bacterial profiling in MLNs demonstrated that <span style="font-style:italic;">Lactobacillus murinus</span> was enriched in B6SKG mice with elevated anti-dsDNA IgG levels. Subcutaneous injection of heat-killed <span style="font-style:italic;">L. murinus</span> induced anti-dsDNA IgG production without altering T- or B-cell subset composition. Immunoblotting and mass spectrometry analysis identified a peptide ATP-binding cassette (ABC) transporter as a molecular mimicry antigen, with its cross-reactivity in lupus mice confirmed by serological assays and <span style="font-style:italic;">in vivo</span> immunization. The <span style="font-style:italic;">L. murinus</span> ABC transporter exhibited surface epitopes that were cross-reactive with sera from lupus mice and patients. The ABC transporter from <span style="font-style:italic;">R. gnavus</span>, known for its pathogenic role in lupus patients, had a similar epitope sequence to that of the <span style="font-style:italic;">L. murinus</span> ABC transporter and reacted with lupus sera.<div class="boxTitle">Conclusion</div>ABC transporters from gut bacteria can serve as cross-reactive antigens that may promote anti-dsDNA antibody production in genetically susceptible mice. These findings underscore the role of commensal-derived molecular mimicry and bacterial translocation in lupus pathogenesis.</span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Objectives</div>Patients with systemic sclerosis present with severe gastroesophageal reflux disease, often refractory to proton-pump inhibitors (PPI) treatment. The aim of the present study was to identify factors associated with PPI-refractory oesophagitis.<div class="boxTitle">Methods</div>We performed a cross-sectional study in a single-centre cohort of patients diagnosed with systemic sclerosis. We included patients who underwent an oesophagogastroduodenoscopy while on PPI treatment. Patients with PPI-refractory erosive oesophagitis were compared with those with endoscopically normal oesophageal mucosa.<div class="boxTitle">Results</div>A total of 69 patients were included. From these, 23 patients (33%) had PPI-refractory oesophagitis (Grade A, <span style="font-style:italic;">n</span> = 11; Grade B, <span style="font-style:italic;">n</span> = 7; Grade C, <span style="font-style:italic;">n</span> = 2; Grade D, <span style="font-style:italic;">n</span> = 3) and 46 (67%) had an endoscopically normal oesophageal mucosa. On univariate analysis, patients with PPI-refractory oesophagitis were more frequently diffuse SSc subset (43% <span style="font-style:italic;">vs</span> 17%; <span style="font-style:italic;">P</span> = 0.041). Evaluating gastrointestinal motility tests, neither absent oesophageal contractility (39% <span style="font-style:italic;">vs</span> 25%, <span style="font-style:italic;">P</span> = 0.292) nor hypotensive lower oesophageal sphincter (47% <span style="font-style:italic;">vs</span> 44%, <span style="font-style:italic;">P</span> = 0.980) were significantly associated with PPI-refractory oesophagitis. Gastrointestinal dysmotility, defined as abnormal gastric emptying and/or small bowel dilated loops, was significantly associated with PPI-refractory oesophagitis (66 <span style="font-style:italic;">vs</span> 8%, <span style="font-style:italic;">P</span> =<0.001). On a multivariate regression model to evaluate the association between motility test results adjusted for the diffuse subset, gastrointestinal dysmotility (β = 0.751, <span style="font-style:italic;">P</span> = 0.010) was independently associated with PPI-refractory oesophagitis, while absent oesophageal contractility (β = 0.044, <span style="font-style:italic;">P</span> = 0.886) or a hypotensive LES were not (β = −0.131, <span style="font-style:italic;">P</span> = 0.663).<div class="boxTitle">Conclusions</div>Our findings suggest that gastric and small intestinal motor dysfunction may be an important contributor to the development of PPI-refractory oesophagitis in patients with systemic sclerosis. </span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Objectives</div>Systemic sclerosis (SSc) is heterogeneous in its clinical presentation. Common manifestations cluster together, defining unique subgroups. This investigation aims to characterize gastrointestinal (GI) phenotypes and determine whether they can be distinguished by temporal progression.<div class="boxTitle">Methods</div>We examined a well-established SSc patient cohort with a modified Medsger GI severity score measured over time to determine heterogeneity in disease progression. Growth mixture models estimated each patient's phenotype and disease severity trajectory over time. We compared the characteristics of estimated phenotypes using non-parametric statistics and linear and logistic regression to compare patient characteristics between phenotypes while adjusting for disease duration.<div class="boxTitle">Results</div>We examined 2696 SSc patients with at least two Medsger GI scores, identifying four unique phenotypes. The most common phenotype (‘Stable’, <span style="font-style:italic;">n</span> = 2325) had an average score of 1 that was consistent over time. Two phenotypes were progressive (‘Early Progressive’, <span style="font-style:italic;">n</span> = 142, and ‘Late Progressive’, <span style="font-style:italic;">n</span> = 115) with an initial average score of 1. The Early Progressive group increased initially and stabilized, and the Late Progressive group worsened slowly over time. A fourth phenotype (‘Early Severe GI’, <span style="font-style:italic;">n</span> = 114) had an initial average Medsger GI score just below 3 with high mortality and improving GI severity over time.<div class="boxTitle">Conclusions</div>Clinically distinct GI phenotypes exist among patients with SSc. These phenotypes are not only distinguished by GI and extra-intestinal SSc clinical complications, but they are also temporally distinct. Distinct autoantibody profiles are associated strongly with more severe GI disease.</span>
<span class="paragraphSection"><span style="text-transform:lowercase;font-variant:small-caps;">Dear Editor</span>, The recent study by Gelsomina Alle <span style="font-style:italic;">et al.</span> [<a href="#keae468-B1" class="reflinks">1</a>] has revealed that in pregnant patients with SLE, low HCQ whole blood concentrations in the first trimester, below the therapeutic threshold (≤500 ng/ml) and severe non-compliance levels (≤200 ng/ml), are closely associated with severe maternal flares but not significantly with adverse pregnancy outcomes (APOs). This finding highlights the importance of monitoring HCQ levels for predicting disease activity during pregnancy in SLE patients. However, there are several key issues within the study that may affect the accuracy and interpretation of its results.</span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Objectives</div>Anti-melanoma differentiation–associated gene 5 antibody–positive (MDA5<sup>+</sup>) DM patients exhibit clinical features that vary by geographical and ethnic/genetic distribution. The objective of this study was to investigate whether B cell epitope profiles and corresponding clinical features distinguished two independent cohorts of MDA5<sup>+</sup> DM.<div class="boxTitle">Methods</div>ELISA-based methods were used to determine the relationship between antibody recognition of 155 overlapping amino acid MDA5 subfragments and clinical features of 17 MDA5<sup>+</sup> DM patients from Japan. Associations between clinical features and standardized anti-MDA5 subfragment antibody titres were assessed via Brunner Munzel testing and compared with the clinical/serological profiles of an independent North American cohort. Receiver operater characteristic (ROC) analyses and Kaplan–Meier curves were used to further assess the relationship between anti-MDA5 fragment antibody levels and specific clinical features/outcomes.<div class="boxTitle">Results</div>Clinical characterization of a Japanese cohort of 17 MDA5<sup>+</sup> DM patients revealed a high prevalence of arthritis (47%) and interstitial lung disease (ILD) (100%). Serological profiling demonstrated predominant antibody recognition of MDA5 fragments A (aa 1–155), B (aa 130–284) and E (aa 517–671) in a pattern that was distinct from North American MDA5<sup>+</sup> patients (<span style="font-style:italic;">n</span> = 24), whose sera preferentially recognized fragment H (aa 905–1026). Statistical analysis revealed a striking association between anti-fragment A antibody levels and rapidly progressive ILD (RP-ILD) among Japanese patients (<span style="font-style:italic;">P</span> < 0.01). ROC and Kaplan–Meier curves also demonstrated a strong relationship between anti-fragment A antibody levels, RP-ILD, and pulmonary death in combined cohort analyses.<div class="boxTitle">Conclusions</div>Japanese and North American MDA5+ DM patients manifest markedly different B cell epitope profiles that are associated with higher prevalence of RP-ILD and worse clinical outcome among Japanese patients.</span>
<span class="paragraphSection"><span style="text-transform:lowercase;font-variant:small-caps;">Dear Editor</span>, We thank Weizhen Tang <span style="font-style:italic;">et al.</span> for their interest in our study on HCQ blood concentrations in pregnant patients with SLE and their association with maternal and foetal outcomes [<a href="#keae449-B1" class="reflinks">1</a>]. However, we would like to clarify several points that appear to have been misunderstood or overlooked.</span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Objectives</div>To assess the maintenance of efficacy of one year of tocilizumab (TCZ) monotherapy after its discontinuation in large vessel-GCA (LV-GCA).<div class="boxTitle">Methods</div>17 patients with active LV-GCA were previously treated with 3 boluses of intravenous methylprednisone and weekly subcutaneous TCZ in monotherapy for 52 weeks. Patients in relapse-free clinical remission at week 52 discontinued TCZ and entered part two, which was a 26-week observational follow-up period. PET/CT was performed in all patients at the end of the 26-week observational period (week 78). End points were the variation in PET vascular activity score (PETVAS) at week 78 compared with baseline and with week 52, and the proportion of patients with relapse-free clinical remission at week 78 and at the end of the follow-up.<div class="boxTitle">Results</div>Compared with baseline, a significant reduction in PETVAS was observed at week 78, mean (95% CI) change −6.6 (−9.5 to −3.7). However, compared with week 52, PETVAS significantly increase 6 months after TCZ discontinuation (week 78), mean (95% CI) change 4.6 (0.7–8.5). The proportion of patients with relapse-free clinical remission at weeks 78 and at the end of the follow-up (median time from TCZ discontinuation 148 weeks) was 11/17 (65%, 95% CI 38–86) and 8/17 (47%, 95% CI 23–72), respectively. Age and sex-adjusted HR (95% CI) for each unit increase of PETVAS indicating subsequent relapse was 1.36 (0.92–2.00).<div class="boxTitle">Conclusions</div>One year of TCZ monotherapy was effective in maintaining drug-free clinical remission in LV-GCA. Changes in PETVAS early after TCZ discontinuation may predict subsequent relapses.<div class="boxTitle">Trial registration</div>ClinicalTrials.gov, <a href="http://clinicaltrials.gov">http://clinicaltrials.gov</a>, NCT05394909.</span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Objectives</div>SSc is characterized by widespread microangiopathy and fibrosis of skin and visceral organs. Left ventricle involvement is usually subclinical, characterized by systolic and/or diastolic dysfunction. The global longitudinal strain (GLS), a validated and reliable technique for the measurement of ventricular longitudinal deformation by means of echocardiography, may detect subclinical systolic dysfunction of SSc myocardium. The improvement of myocardial perfusion by means of intravenous Iloprost administration could ameliorate the contractility of SSc heart. Therefore, we aimed to evaluate GLS in a series of SSc patients prior and after Iloprost infusion.<div class="boxTitle">Methods</div>Fifteen consecutive SSc patients (age: 54 ± 11 years; 12 females) treated with Iloprost because of the presence/history of digital ulcers underwent echocardiography, including GLS technique. This evaluation was conducted immediately before Iloprost administration and at the end of the 6-h infusion session.<div class="boxTitle">Results</div>Significant improvement in the mean GLS was observed after Iloprost administration (from −13.5 ± 2.5 to −15 ± 3.3; <span style="font-style:italic;">P</span> = 0.011). The echocardiographic data obtained from the four-chamber view showed the best quality for GLS analysis and showed a highly significant improvement of the strain after Iloprost administration (from −13.4 ± 2.2 to −15.6 ± 3; <span style="font-style:italic;">P</span> = 0.001). The degree of GLS improvement did not correlate with any SSc parameters.<div class="boxTitle">Conclusion</div>Iloprost administration improved GLS, suggesting that the increase of myocardial perfusion allowed, at least in part, a correction of left ventricular systolic dysfunction. Further studies are needed to confirm these findings, further exploring the mid/long-term effects of Iloprost on myocardial contraction.</span>
<span class="paragraphSection"><span style="text-transform:lowercase;font-variant:small-caps;">Dear Editor</span>, The study by Zhao <span style="font-style:italic;">et al.</span> [<a href="#keae347-B1" class="reflinks">1</a>]. highlights the psychological challenges faced by patients with early inflammatory arthritis and underscores the significant impact of psychological distress on clinical outcomes and quality of life over a 12-month period. We commend the authors for their focus on this population, which is crucial for promoting health equity and enhancing targeted interventions. This letter aims to appreciate the study’s contributions while discussing areas requiring cautious interpretation and further investigation.</span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Objectives</div>To elucidate the long-term outcomes of patients with difficult-to-treat rheumatoid arthritis (D2T RA).<div class="boxTitle">Methods</div>We collected data on the clinical course of patients who had been identified as D2T RA in 2018 until 2023. We stratified the patients according to outcomes at the last visit: resolved D2T RA, persistent D2T RA and mortality. We compared their clinical characteristics and investigated the predictive factors for the resolution of D2T RA or mortality. Furthermore, we investigated the impact of the causes of D2T RA identified in 2018, multidrug resistance, comorbidities and socioeconomic factors on outcomes in 2023.<div class="boxTitle">Results</div>Of 173 patients identified as D2T RA in 2018, 150 were included in the analysis. Among them, D2T RA was resolved in 67 (45%), 75 (50%) remained as D2T RA, and 8 (5%) died. Patients with resolved D2T RA were significantly younger at the latest visit (<span style="font-style:italic;">P</span> = 0.02), had a higher proportion of treatment changes during five years (<span style="font-style:italic;">P = </span>0.002), and had a higher proportion of interleukin-6 receptor inhibitors use in 2023 (<span style="font-style:italic;">P = </span>0.04) than those in patients with persistent D2T RA or those who died. D2T RA resolved in 38% of patients with multidrug resistance, mainly with treatment changes. Rheumatic disease comorbidity index and glucocorticoid dose escalation were independent risk factors for mortality [odds ratio (OR), 3.50; <span style="font-style:italic;">P = </span>0.02 and OR, 31.9; <span style="font-style:italic;">P = </span>0.002, respectively].<div class="boxTitle">Conclusion</div>Further modifications in RA treatment are useful for resolving D2T RA. Multiple comorbidities and glucocorticoid use are associated with mortality.</span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Objectives</div>Current guidelines recommend pneumococcal vaccination in individuals who are over the age of 65 or are immunosuppressed due to a disease or treatment. The objective of this study was to assess vaccine uptake rates in people with inflammatory arthritis for the pneumococcal, influenza and Covid-19 vaccines and factors determining uptake.<div class="boxTitle">Methods</div>We conducted a retrospective single centre cohort study in the UK of individuals with rheumatoid arthritis, psoriatic arthritis and axial spondyloarthritis between October and December 2023. Data were collected for age, gender, co-morbidities, immunosuppressive therapies and dates of vaccines. Logistic regression was used to evaluate predictors of vaccine uptake, with adjustments for demographic and clinical factors.<div class="boxTitle">Results</div>Nine hundred and six individuals were identified; 46% were receiving treatment with conventional synthetic DMARD (csDMARD), 26% were on biologic monotherapy, and 23% were on both biologic and csDMARDs. Three hundred and sixteen individuals (35%) received a pneumococcal vaccine, lower than uptake for influenza (63%) and Covid-19 (87%) vaccines. Predictors of pneumococcal vaccine uptake included age, with older patients more likely to be vaccinated (odds ratio [OR] for age ≥ 65 years: 1.67; 95% CI: 1.21, 2.29). Those on biologic therapy demonstrated higher likelihood of vaccination (OR for biologic therapy: 1.81; 95% CI: 1.33, 2.47). Additional Joint Committee on Vaccination and Immunisation Green Book indicators also positively influenced vaccine uptake (OR: 1.67; 95% CI: 1.19, 2.33).<div class="boxTitle">Conclusion</div>Pneumococcal vaccine uptake in inflammatory rheumatic diseases is low, especially in younger patients and those not on biologic therapy. The study highlights the need for a focused approach, distinct from strategies for other vaccines, to address this public health challenge.</span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Objective</div>PMR is an age-related inflammatory disease of unknown cause. We aimed to identify potentially modifiable risk factors and therapeutic targets for preventing or treating PMR.<div class="boxTitle">Methods</div>We meta-analysed genetic association data from 8156 cases of PMR (defined using diagnostic codes and self-report) and 416 495 controls of European ancestry from the UK Biobank and FinnGen. We then performed Mendelian randomization analyses to estimate the association between eight modifiable risk factors (using data from up to 1.2 million individuals) and 65 inflammation-related circulating proteins (up to 55 792 individuals), using the inverse variance weighted and pleiotropy robust methods.<div class="boxTitle">Results</div>We identified three novel genome-wide significant loci in the <span style="font-style:italic;">IL1R1</span>, <span style="font-style:italic;">NEK6</span> and <span style="font-style:italic;">CCDC88B</span> genes and confirmation of previously described associations with <span style="font-style:italic;">HLA-DRB1</span> and <span style="font-style:italic;">ANKRD55.</span> Genetically predicted smoking intensity (OR 1.32; 95%CI 1.08–1.60; <span style="font-style:italic;">P</span> = 0.006) and visceral adiposity (OR 1.22; 95%CI 1.10–1.37; <span style="font-style:italic;">P</span> = 3.10 × 10<sup>−4</sup>) were associated with PMR susceptibility. Multiple circulating proteins related to IL-1 family signalling were associated with PMR. IL-1 receptor-like 2, also known as IL-36 receptor (OR 1.25; <span style="font-style:italic;">P</span> = 1.89 × 10<sup>−32</sup>), serum amyloid A2 (OR 1.06, 9.91 × 10<sup>−10</sup>) and CXCL6 (OR 1.09, <span style="font-style:italic;">P</span> = 4.85 × 10<sup>−7</sup>) retained significance after correction for multiple testing.<div class="boxTitle">Conclusion</div>Reducing smoking and visceral adiposity at a population level might reduce incidence of PMR. We identified proteins that may play causal roles in PMR, potentially suggesting new therapeutic opportunities. Further research is needed before these findings are applied to clinical practice.</span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Objectives</div>People with inflammatory arthritis (IA) experience worsened mental wellbeing alongside disease progression. Using the National Early Inflammatory Arthritis Audit (NEIAA), we assessed trends in psychological distress during the 12 months following IA diagnosis, mapping these against clinical outcomes to identify associations.<div class="boxTitle">Methods</div>This is a prospective study of people recruited to NEIAA receiving an IA diagnosis and completing the baseline patient survey. Patient-reported outcomes (PROs) at baseline, 3 months and 12 months were collected, including psychological distress [assessed using Patient Health Questionnaire Anxiety and Depression Screener (PHQ4ADS)]. Mixed effects linear regression models estimated associations between predictor variables with psychological distress at baseline and over time.<div class="boxTitle">Results</div>Of 6873 eligible patients, 3451 (50.2%) showed psychological distress at baseline. Of those completing follow-ups, 30.0% and 24.1% were distressed at 3 months and 12 months, respectively. Higher psychological distress at diagnosis was more commonly reported by younger, female and non-White patients. Clinical factors, including higher counts of comorbidities, prior depression and higher disease activity at diagnosis were associated with higher distress. Higher distress at baseline was associated with poorer outcomes over time in quality of life, disability, work performance, disease activity, as well as reduced likelihood of achieving good treatment response by EULAR criteria.<div class="boxTitle">Conclusion</div>Half of patients with IA show significant mental health comorbidity at presentation, which associated with worse disease outcomes and quality of life. Screening for anxiety and depression should be a universal standard, and access to effective mood therapies alongside arthritis treatments is essential. Strategies should be culturally valid and consider multi-morbidities.</span>
<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Objectives</div>To discern predictive factors for incident kidney involvement in patients with SLE.<div class="boxTitle">Methods</div>Patients with SLE from the ‘Attikon’ Lupus cohort were monitored for LN, defined by kidney histology and/or classification criteria. Demographic and clinical characteristics at baseline were compared against patients who did not develop LN. LN-free Kaplan–Meier survival curves were generated. A multivariate Cox proportional hazards model was used to identify independent predictors of LN. Independent validation was performed in the University of Crete Lupus registry.<div class="boxTitle">Results</div>Among the 570 patients in the derivation cohort, 59 exhibited LN as their initial presentation, while an additional 66 developed LN during the follow-up period (collectively, 21.9% incidence). In the latter group, baseline factors predictive of subsequent kidney involvement were male sex [multivariable-adjusted hazard ratio (aHR) 4.31; 95% CI: 1.82, 10.2], age of SLE diagnosis below 26 years (aHR 3.71; 95% CI: 1.84, 7.48), high anti-dsDNA titre (aHR 2.48; 95% CI: 1.03, 5.97) and low C3 and/or C4 (although not statistically significant, aHR 2.24; 95% CI: 0.83, 6.05; <span style="font-style:italic;">P</span> = 0.11). A combination of these factors at time of diagnosis conferred an almost 90-fold risk compared with serologically inactive, older, female patients (aHR 88.77; 95% CI: 18.75, 420.41), signifying a very high-risk group. Independent validation in the Crete Lupus registry showed concordant results with the original cohort.<div class="boxTitle">Conclusion</div>Male sex, younger age and serological activity at SLE diagnosis are strongly associated with subsequent kidney involvement. Vigilant surveillance and consideration of early use of disease-modifying drugs is warranted in these subsets of patients.</span>
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