This study aimed to investigate real-world clinical practices regarding biologic therapy in colchicine-resistant familial Mediterranean fever (FMF), focusing on treatment initiation, tapering, discontinuation strategies, and related challenges. A 29-item English-language survey was distributed to pediatric and adult rheumatologists via email. The target population consisted of rheumatologists from Türkiye, Israel, and Italy (countries with a high prevalence of FMF) as well as Germany, where migrants of eastern Mediterranean origin live. The survey addressed preferences for biologic agents, colchicine compliance, tapering strategies, injection-site reaction management, and responses to trigger-related attacks. A total of 126 clinicians responded. In the absence of regulatory constraints, 72.2% preferred canakinumab for colchicine-resistant FMF. The majority (94.4%) considered the standard dose of 2 mg/kg/day sufficient. Gradual extension of dose intervals was the most common tapering strategy. Whereas canakinumab was often tapered to dosing intervals of every 3-4 months, anakinra was tapered by extending the dosing interval to weekly administration in some cases. More than half (53.9%) observed a decline in colchicine compliance after starting biologics. Although 51.7% and 53.3% reported full efficacy after restarting anakinra and canakinumab, respectively, some clinicians noted reduced responses. Adult rheumatologists were more likely than pediatricians to support lifelong biologic therapy and reported greater concerns regarding colchicine compliance. Pediatric rheumatologists tended to favor discontinuation of biologic therapy rather than lifelong use. On-demand use of biologics also emerged as a treatment approach among treating physicians. Issues such as colchicine compliance, disease-specific triggers, and the potential to maintain efficacy upon reintroduction of interleukin 1 inhibitors after discontinuation should be prioritized in future research.

To evaluate clinical and epidemiological features of juvenile-onset systemic sclerosis (jSSc) in Japan and to identify racial and generational differences. We surveyed patients with jSSc (developed < 18 years of age) who visited selected facilities in Japan between January 2016 and December 2020. We estimated the number of patients with jSSc and the annual incidence rate in Japan. Thereafter, differences in clinical characteristics by disease subtype, autoantibody, and age at investigation were analyzed and compared with previous cohorts. Of the 3005 institutions selected for the first survey, 1845 (61.4%) responded. The estimated number of patients with jSSc was 299, whereas the estimated annual incidence rate ranged from 0.98 to 1.59 per 1 million children (aged < 18 years) from 2016 to 2020. In the second-stage survey, 130 cases were analyzed, of which 85 (65.4%) had diffuse cutaneous SSc (dcSSc), 77.7% were female, and the median ages at onset and during the survey were 11 and 21 years, respectively. Autoantibody positivity was 62.4% for antitopoisomerase I antibody (ATA) and 12.9% for anticentromere antibody, whereas anti-PM/Scl antibody was very rare. In total, interstitial lung disease was present in 40.8% of patients (predominantly dcSSc and ATA positive), gastrointestinal lesions in 36.9%, pulmonary arterial hypertension in 7.7%, and no renal crisis. This is the largest national survey of jSSc characteristics analyzed in detail by autoantibody and disease subtype. Japanese jSSc was characterized by a very high ATA positivity rate. However, the frequency of major organ involvement was similar to previous reports of jSSc in the West.

Systemic sclerosis (SSc) gastrointestinal disease is heterogeneous in presentation, with individual symptoms lacking specificity for specific anatomical and functional abnormalities. We used factor analysis to investigate whether latent subgroups of SSc gastrointestinal symptoms can be detected. Using SCTC UCLA Gastrointestinal 2.0 Questionnaire (GIT 2.0) data from 773 Australian Scleroderma Cohort Study participants, we performed a factor analysis of firstly, GIT 2.0 domains scores and then, individual GIT 2.0 question responses to identify latent factors. A subsequent cluster analysis was performed to explore whether clinically definable SSc phenotypes were associated with specific gastrointestinal symptoms. SSc gastrointestinal symptoms were highly correlated. Factor analysis of individual GIT 2.0 question responses revealed four latent factors within the dataset that could be clinically described as upper gastrointestinal tract symptoms, bloating, diarrhoea and incontinence, and constipation. Cluster analysis revealed two patient clusters, distinguished by disease duration and severity of gastrointestinal manifestations. Anti-centromere antibodies and pulmonary arterial hypertension were more common in participants with severe gastrointestinal disease. Despite the high correlation between gastrointestinal manifestations, it is possible to detect subgroups of SSc gastrointestinal symptoms. Improved understanding of these subgroups of SSc gastrointestinal disease may advance the discovery of targeted interventions to improve the daily function and quality of life of those living with SSc.

To describe the clinical and laboratory findings, disease course, and treatment effectiveness of a large, genetically homogenous group of patients with deficiency of adenosine deaminase 2 (DADA2), and to identify factors associated with disease-related damage. We conducted a retrospective cohort study that included 45 patients with DADA2 vasculitis with long-term follow-up. Information was collected from patients' charts, including demographic information, clinical presentations, laboratory findings, and treatment. The extent of disease-related damage was determined based on the Vasculitis Damage Index. In this large homogenous cohort, we found that a young age at disease onset and periodic illness that included recurrent episodes of fever, myalgia, and abdominal pain were associated with disease-related damage. Patients with severe DADA2 disease responded favorably to tumor necrosis factor inhibitors (TNFi). Early age of onset and the periodic nature of the disease warrant prompt initiation of TNFi treatment to prevent later complications and severe disease progression.

To evaluate the association between the daily GC dose and various patient-reported outcomes (PROs) in patients who have achieved lupus low disease activity state (LLDAS). Patients from a single-center cohort were included. PROs included were the FACIT-F (Functional Assessment of Chronic Illness Therapy-Fatigue), the LupusQoL (Lupus Quality of Life), the physical and mental component summary measures of the SF-36 (36-Item Short Form Health Survey) and the LFA-REAL PRO (Lupus Foundation of America Rapid Evaluation of Activity in Lupus PRO). Univariable and multivariable generalized estimating equations (GEE) were performed; the multivariable models were adjusted for possible confounders: age at diagnosis, sex, socioeconomic status, educational level, ethnicity, disease duration, disease activity and damage, antimalarial and immunosuppressant use. In an alternative analysis, GEE were also performed with patients categorized on the basis of 4 prednisone dose categories: 0mg, >0mg & ≤2.5mg, >2.5mg & ≤5mg and >5mg & ≤7.5mg. Three-hundred and twenty-four patients and 1338 LLDAS visits were included. In the adjusted analysis, the daily GC dose was associated with worse FACIT-F, LFA-REAL PRO and four out of the eight domains of the LupusQoL scores. In the alternative analysis, after adjustment, the patients in the high GC dose category had a trend of worse PRO scores in the adjusted analysis and the ones in the lower GC dose category showed a trend of better PRO scores. The daily GC dose is associated with worse PROs in SLE patients on LLDAS, even after adjusting for possible confounders.

The efficacy of nucleic acid-based vaccines against SARS-CoV-2 varies across individuals, partly due to genetic factors influencing neutralizing antibody production. In patients with systemic autoimmune diseases (SADs), this response may be further altered by immune dysregulation. We conducted a genome-wide association study (GWAS) to identify genetic variants associated with postvaccination anti-SARS-CoV-2 IgG antibody levels and to assess whether these associations differ between patients with SAD and healthy individuals. The study included 165 participants (138 with SADs, 27 healthy controls), all of whom received nucleic acid-based vaccines. Antibody levels targeting the spike protein receptor-binding domain (RBD) and nucleocapsid were measured between 1 and 12 months after vaccination. GWAS results were metaanalyzed with data from a previously published GWAS with 1076 healthy individuals. We identified a novel association near RACGAP1 (rs706785; βmeta = -0.30, P meta = 3.85 × 10-8) and replicated a known association at HLA-DRB1 position 71 (βmeta = -0.23, P meta = 1.94 × 10-11). No significant interactions were observed between genotype and disease status. This study highlights both MHC and non-MHC genetic contributions to SARS-CoV-2 vaccine responses and suggests these effects are consistent across patients with SADs and healthy individuals, supporting standard vaccination strategies for individuals with systemic autoimmune conditions.

To compare five Health Assessment Questionnaire (HAQ) scoring methods to measure functional disability among people with systemic sclerosis (SSc, scleroderma). Scleroderma Patient-centered Intervention Network Cohort participants completed the Health Assessment Questionnaire (20 items, 8 domains) at enrolment. We calculated HAQ Disability Index (HAQ-DI) scores, which sum the highest item score for each domain and account for the use of aids, devices, or assistance; Alternative Disability Index (HAQ-ADI) scores, which are calculated similarly but do not account for aids, devices, or assistance; Modified HAQ (MHAQ) scores, which are based on one administered item from each domain, as well as a simple summed score of all 20 items. We then compared these scores and those generated from an Item Response Tree (IRTree) on convergent validity with physical function, pain interference, and hand function using Pearson's correlations. IRTree-based scores were highly correlated (r = 0.90 to 0.95) with other scoring procedures and showed moderate-to-strong correlations with all external measures (r = 0.68 to 0.80). There was no evidence of a difference between IRTree-based and HAQ-DI correlations with external measures. IRTree-based scores performed better than HAQ-ADI, MHAQ, and summed scores for physical function and pain interference but worse for hand function. IRTree-based scoring is a novel approach that incorporates information from all HAQ items and whether participants use aids, devices, or assistance. Its association with external measures, however, did not differ from the standard HAQ-DI. HAQ-DI scoring is easy to implement, and extensive comparative data are available, making it the preferred scoring method.

To evaluate the relationship between major life stressors in the year prior to diagnosis and rheumatoid arthritis (RA) symptoms and function at diagnosis and at 1 year. Data were from adults with RA in the Canadian Early Arthritis Cohort, a multicenter inception cohort from January 2007 to March 2017 with ≥ 12 months of follow-up. Patients completed questionnaires about stressful life events in the prior year: Health Assessment Questionnaire-Disability Index (HAQ-DI); 12-item Short Form Health Survey; and 11-point rating scales of sleep, fatigue, pain, and patient global assessment (PtGA). Group characteristics were compared with ANOVA or chi-square test, and adjusted multivariable regression models examined the effect of stressors on symptoms and function at 1 year. The 1933 participants were mostly White (87%) women (72%) with a mean age of 55 years; 52% reported ≥ 1 stressors in the year prior to diagnosis. Around diagnosis, patients reporting major stressors had significantly worse mean HAQ-DI, depression, sleep, fatigue, pain, and PtGA, which generally worsened with the type and number of stressors. At 1 year, the odds of depression and disability, and ratings of pain, fatigue, poor sleep, and PtGA generally increased with an increasing number of stressors, though Simplified Disease Activity Index (SDAI) improved similarly among groups. Fifty-two percent of patients with newly diagnosed RA reported stressful life events in the year prior to diagnosis that were associated with worse disability, depression, pain, fatigue, sleep, and well-being, but not SDAI, at diagnosis. Poorer patient-reported outcomes persisted at 1 year despite similar improvements in SDAI. Results highlight the potential independent contributions of environmental and psychological factors in the onset and course of RA.