OBJECTIVE:We compared demographic and clinical characteristics between patients with late-onset (LO) and early-onset (EO) systemic lupus erythematosus (SLE) and examined their longitudinal associations with treatment targets and long-term outcomes, irreversible organ damage accrual and health-related quality of life (HRQoL). METHODS:We analyzed prospectively collected data from patients enrolled in the Asia Pacific Lupus Collaboration cohort. Patients diagnosed with SLE at age >50 years were classified as LO-SLE and compared with those diagnosed at age ≤50 years (EO-SLE). Longitudinal associations with treatment targets (LLDAS and DORIS remission), organ damage accrual (SLICC/ACR Damage Index), and HRQoL (SF36v2 physical and mental component summary (PCS and MCS) scores) were examined using multivariable multilevel logistic, recurrent-event survival, and linear mixed-effects models, respectively. Disease activity, flares, medication exposure, and other clinical characteristics were also compared between groups. RESULTS:Among 3,917 patients studied, 346 (8.8%) had LO-SLE. Compared with EO-SLE, patients with LO-SLE had lower disease activity, lower glucocorticoid and immunosuppressant exposure, and higher attainment of treatment targets; LO-SLE was associated with higher odds of attaining LLDAS (OR: 2.33 (1.66, 3.28)) and DORIS remission (OR: 2.22 (1.45, 3.38)). However, they were at a greater risk of damage accrual (HR:1.82 (1.50, 2.21)) and lower PCS scores, meaning poorer physical health (regression coefficient (RC) = -3.63 (-4.58, -2.68)) but not MCS (RC= 0.68 (-.50, 1.86)). CONCLUSION:Despite higher attainment of treatment targets, patients with LO-SLE experienced greater damage accrual and poorer physical health, suggesting that disease activity targets alone may not fully capture outcome risk in LO-SLE.
Mendelian randomisation (MR) has become abundant in the literature, with variation in quality and frequent overinterpretation of causality. This creates a problem for clinical readers, reviewers, and editors: some MR studies can sharpen causal thinking, prioritise drug targets, and challenge misleading observational claims, whereas others are little more than automated exposure-outcome scans with causal claims disproportionate to the evidence. MR can strengthen causal inference when randomised trials are impractical and conventional observational studies are vulnerable to confounding, reverse causation, or selection bias. In rheumatology, credible MR can contribute to questions about disease aetiology, modifiable risk factors, therapeutic target validation, adverse-effect anticipation, and phenotype validation. However, its interpretation depends on whether the exposure is plausibly instrumentable, whether the genetic instruments are biologically defensible, whether assumptions are interrogated in ways appropriate to the design, and whether findings are triangulated with clinical, observational, experimental, and mechanistic evidence. Instead of recapitulating all methodological issues of MR, this review aims to help rheumatologists distinguish robust MR from weak or overinterpreted analyses quickly. We provide an accessible framework for reading and triaging MR studies in rheumatology. Papers that use poorly justified instruments, treat medication use as drug-target evidence, interpret genetic liability as diagnosis, rely on mechanical sensitivity analyses, ignore prior evidence or ask no clinically meaningful question can often be passed over by readers. The goal is not to discourage MR in rheumatology, but to raise the standard; useful MR should clarify causal reasoning rather than simply generate another statistically significant association.
OBJECTIVE:To evaluate remission rates in axial spondyloarthritis (axSpA) using cross-sectional data. METHODS:Adult patients with axSpA and ≥2 prior visits were included. Patient's characteristics and outcome measures for disease activity and physical function were documented at enrolment (enrolment visit). Remission was defined as ASDAS <1.3 and sustained remission (SR) as ASDAS <1.3 for at least 6 consecutive months. Multivariable logistic regression was used to estimate ORs, 95% CIs and p-values for factors associated with remission. RESULTS:200 patients were studied for a mean 82.6 (SD 58.6) months. ASDAS at enrolment visit was 2.0 (1.0). 117 patients (58.5%) achieved ASDAS remission at least once during observation. Remission was reached 37.7 (44.5) months after start of treatment in our hospital (index visit). 44 patients achieved remission within the first year (37.6%), 20 (17.1%), 13 (11.1%) and 40 (34.2%) after 1, 2 and 3 years, respectively. Remission duration was 9.9 (16.8) months. 51 patients (43.6%) achieved sustained remission for ≥ 6 consecutive months. High CRP (OR 1.35 (1.10, 1.73)) and lower BASDAI (OR 0.72 (0.53, 0.97)) at index visit were associated with achieving remission at least once. CONCLUSION:Remission is an attainable outcome for patients with axSpA in usual care. High CRP and low BASDAI at index visit were associated with remission. Most patients were in remission within the first two years of treatment but there were also patients whose first remission were after more than five years of follow up.
OBJECTIVE:To identify and characterize unobserved subgroups of patients with axial spondyloarthritis (axSpA) based on response patterns to the Assessment of SpondyloArthritis International Society Health Index (ASAS HI) using latent class analysis (LCA). METHODS:We conducted LCA on 17 dichotomous ASAS HI items in a cohort of 180 axSpA patients. Models with 2-6 classes were evaluated using Bayesian and Akaike Information Criteria, selecting the optimal model based on the lowest BIC. Class profiles were defined by conditional item endorsement probabilities. Construct validity analyses included comparisons of BASDAI, BASFI, ASDAS, and total ASAS HI scores. Internal validation was performed via bootstrap resampling. Secondary multinomial logistic regression assessed the influence of disease indices on class membership. RESULTS:A five-class model showed distinct health impact profiles. Class 1 (n=25, 13.9%) exhibited the highest burden across physical, emotional, and motivational domains, while Class 2 (n=63, 35%) showed minimal impact. Intermediate classes reflected predominant physical (Class 3, n=35), fatigue (Class 4, n=18), or functional (Class 5, n=36)) impairment patterns. Significant differences in BASDAI, BASFI, ASDAS, and ASAS HI total scores were observed across classes (all p < 0.001). Combined multinomial regression models including BASDAI, ASDAS, and BASFI showed a pseudo-R² of 0.33 for class allocation. Posterior classification probabilities were high (mean = 0.88), and bootstrap analysis confirmed model stability. CONCLUSION:LCA of ASAS HI responses identified five distinct and clinically meaningful health impact profiles in axSpA. These findings highlight the multidimensional burden of axSpA and support the potential role of PROM-based stratification.
OBJECTIVE:To assess whether early-life antibiotics are associated with spondyloarthritis (SpA) diagnosed by age 21. METHODS:In this population-based, matched case-control study, we used Danish live births (1997-2023) restricted to those reaching the following minimum relevant ages by December 31, 2024: 1-21 years for psoriatic arthritis (PsA), and 6-21 years for peripheral/axial SpA and inflammatory bowel disease (IBD)-associated arthritis. Cases (n = 560) had physician-recorded SpA (peripheral/axial SpA, PsA, or IBD-associated arthritis). Controls were matched 1:50 by birth year, sex, and calendar year of diagnosis. Primary exposure was systemic antibiotic use the first year of life; secondary exposures included antibiotic class, number of courses, delivery mode, early upper respiratory tract infection (URTI), and systemic nonbacterial antimicrobials. Conditional logistic regression estimated adjusted odds ratios (aORs); dose response was tested with the Wald test. RESULTS:Among cases (median age 16.8 years; 59% peripheral/axial SpA, 28% PsA, 13% IBD-associated arthritis), 50% received antibiotics, vs 42% of controls. First-year antibiotic exposure was associated with higher odds of SpA (aOR 1.35, 95% CI 1.14-1.59). Broad-spectrum penicillins had the strongest class-specific association (aOR 1.42, 95% CI 1.19-1.70). Early URTI was independently associated with SpA (aOR 1.88, 95% CI 1.32-2.67); delivery mode and systemic nonbacterial antimicrobials were not. In SpA subgroup analysis, the association with first-year antibiotics was significant only for PsA (aOR 1.75, 95% CI 1.27-2.41). CONCLUSION:Antibiotic exposure in the first year of life, particularly broad-spectrum penicillins, was associated with increased odds of SpA by age 21, supporting the hypothesis that early-life microbiome disruption may increase later SpA risk.
OBJECTIVE:This study aimed to evaluate serum phoenixin-14 (PNX-14) levels in patients with familial Mediterranean fever (FMF) and periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) during both attack and attack-free periods to investigate its potential biomarker value. METHODS:In total, 140 children were included in this cross-sectional study: 46 with FMF, 48 with PFAPA, and 46 healthy children. Blood samples were collected during both febrile and attack-free periods in the patients with FMF and PFAPA, whereas samples from healthy controls were collected at a single timepoint. C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), serum amyloid A (SAA), fibrinogen, and serum PNX-14 levels were evaluated. Serum PNX-14 levels were measured using ELISA. SPSS 25 (IBM) was used for statistical analyses. RESULTS:PNX-14 levels were significantly higher during attack periods in FMF and PFAPA patients compared to attack-free periods and healthy controls (P < 0.001). PNX-14 levels during attack-free periods were also higher in both patient groups than in healthy controls (P < 0.001). Although a positive correlation was observed between PNX-14 levels and CRP (ρ 0.222, P = 0.04), no significant correlation was observed with ESR, SAA, or fibrinogen. No significant associations were observed between PNX-14 levels and disease severity (Pras disease severity score), colchicine treatment duration, or daily colchicine dose in the FMF group. CONCLUSION:PNX-14 may be part of a neuroimmune response aimed at resolving inflammation in autoinflammatory processes and could be a potential immunomodulatory biomarker. PNX-14 may be a complementary indicator reflecting inflammatory burden or the healing process.
OBJECTIVE:To compare the effectiveness and safety of rituximab (RTX) plus mycophenolate mofetil (MMF) versus RTX monotherapy in patients with SSc-ILD. METHODS:We performed a retrospective comparative analysis among adults with radiologically confirmed SSc-ILD treated with rituximab monotherapy or RTX + MMF (MTT) as rituximab-based treatment strategy. The primary outcome was improvement in percent-predicted forced vital capacity (FVC%) of more than 5 percentage points at the end of 2nd year (ΔFVC>+5). Secondary outcomes included longitudinal FVC trajectories over three years, skin involvement, and safety. Longitudinal analyses used linear mixed-effects models, with additional sensitivity analyses using inverse probability of treatment weighting. RESULTS:Among 109 patients (MTT n=42; RTX n=67), baseline FVC% was lower in MTT group (50.6 vs 61.0). At the end of two years ΔFVC>+5 occurred in 69% of patients receiving MTT compared with 33% receiving rituximab alone. Over 3 years, the adjusted mean increase in FVC% was greater in the MTT group than in the monotherapy group (+12.9% vs +4.4%) with early separation of lung-function trajectories that was sustained throughout follow-up. The association between MTT and greater FVC improvement remained consistent across prespecified subgroups, including patients with severe baseline restriction (FVC% <45%). Herpes zoster occurred more frequently in the MTT group, while serious infections were uncommon in both groups. CONCLUSION:In this real-world study, RTX plus MMF was associated with favourable longitudinal FVC% trajectories compared with RTX monotherapy in a non-randomised cohort, despite greater baseline disease severity in the MTT group. These findings support prospective evaluation of MTT particularly in high-risk patients.
Tsai et al compared 1-year health-related quality of life (HRQOL) after juvenile idiopathic arthritis (JIA) diagnosis between 2 Canadian inception cohorts recruited in 2005-2010 (ReACCh-Out) and in 2017-2023 (CAPRI).1 Using the multidimensional Juvenile Arthritis Quality of Life Questionnaire (JAQQ), they reported improved overall HRQOL over the first year in both eras (mean total JAQQ change -0.92 and -0.97, respectively).1.
Objectives Pregnancy outcomes of women with SLE are worse compared to those without immune-mediated inflammatory diseases (IMID). Factors contributing to higher risk may include concomitant corticosteroid or other medication use and active disease in the peripartum period. Despite international recommendations, the uptake of SLE treatments such as antimalarials during pregnancy remain suboptimal. We examined medication use and maternal/neonatal outcomes in a contemporary, population-level, pregnancy-birth cohort. Methods The study population included all singleton pregnancies with ≥22 weeks of gestation, between July 2008 and December 2024 in Alberta, Canada. Previously validated algorithms based on ICD-10 codes were used to identify women with SLE and no IMID. We compared maternal characteristics, comorbidities and neonatal outcomes between no IMID and SLE groups. Dispensation of SLE-related medications was evaluated in 2 time periods (2008-2016; 2017-2024). Proportion of days covered (PDC) during pregnancy for each medication was calculated to estimate adherence. Logistic regression was used to calculate the odds of developing preterm labor when exposed to SLE-related medications after adjusting for maternal factors. Results Among 787,346 pregnancies of 474,197 women, 994 pregnancies were by women with SLE and 786,352 had no IMID. Pregnant women with SLE were more likely to have renal disease (No IMID 5% vs SLE 10.4%), pre-existing hypertension (No IMID 7.6% vs SLE 23.5%), pre-eclampsia/eclampsia (No IMID 4% vs SLE 9.9%) while neonates in mothers with SLE had more congenital anomalies (No IMID 9.8% vs SLE 13%), were smaller for gestational age (No IMID 12.5% vs SLE 16.1%) and had more NICU admissions (No IMID 9.6% vs SLE 20.2%). SLE prescription dispensations included corticosteroids 21%, NSAIDs 5.5%, antimalarials 46.6%, and pregnancy safe DMARDs 9.5%. Mean PDC for anti-malarials increased from 60.6 (SD 30.3) to 72.2 (SD 27.4) between 2008-2016 and 2017-2024. Preterm delivery was more common in women with SLE (17.4%) vs no IMID (7.0%). In multivariable models, factors that were significantly associated with higher risk of preterm delivery in women with SLE included: low PDC (< 40%) of anti-malarials (compared to high PDC (> 80%)); high PDC of corticosteroids (compared to no use); active disease, being married and pre-eclampsia/eclampsia (Table 1). Table 1. Associations between preterm delivery for Albertan women with SLE, level of adherence to corticosteroids and anti-malarials, and maternal characteristics Conclusion Pregnancy-safe medication use has increased over time but peripartum outcomes remain poor for SLE women. Despite use in SLE flares, corticosteroid use may increase risk of preterm labor. Adherence to anti-malarial use during pregnancy may improve outcomes through reduction of flares. Further patient education and close disease monitoring in the peripartum period is recommended. Supported by a CIORA grant
Objectives Interdisciplinary models of care, where rheumatologists provide care collaboratively with interdisciplinary healthcare professionals (IHPs), have the potential to enhance the delivery of rheumatology services, yet their adoption remains limited. This study aimed to identify barriers and enablers to adopting an interdisciplinary model of care, as perceived by rheumatologists. Methods We conducted a qualitative study using semistructured interviews with rheumatologists practicing in Ontario, Canada, whose primary practice was a conventional model of care (without IHPs). Participants were purposively sampled to ensure variation in gender, career stage, practice setting, and region. The interview guide was informed by the Theoretical Domains Framework (TDF), an implementation framework used to identify determinants of health-professional behavior. We used content analysis with deductive coding to TDF domains and inductively derived within-domain themes on factors influencing adoption of interdisciplinary care. Results We interviewed 14 rheumatologists across Ontario (12 adult, 2 pediatric), of whom 9 were women (64%) and 8 were aged <40 (57%). We identified 6 TDF domains as relevant to rheumatologists’ adoption of interdisciplinary care (Table 1), with barriers and enablers varying by anticipated IHP scope/function. Participants described being optimistic they would be able to feasibly implement an interdisciplinary model with appropriate system supports (1-Optimism) and reported strong self-efficacy for training and supervising IHPs (2-Beliefs about capabilities). Participants perceived that adoption would benefit patients (improved access/equity through shorter wait times, better care coordination, improvements in health outcomes) and rheumatologists (reduced administrative workload and burnout), which they identified as key enablers (3-Beliefs about consequences). Funding was described as the primary system-level barrier. For some, limited physical space to accommodate an IHP was reported to further impede adoption. Participants perceived a shortage of suitably trained IHPs, particularly outside urban centers, as a major barrier to adoption. They anticipated that the substantial time required to train new team members, and the risk of turnover, could create non-recoverable training costs and discourage implementation (4-Environmental context and resources). Rheumatologists reported knowledge gaps regarding IHP training and scope, along with limited business and human-resources skills for recruitment and contracting, as barriers to adoption (5-Knowledge, 6-Skills). Table 1 Adoption of interdisciplinary rheumatology care: TDF domains with themes and illustrative quotes Conclusion Among rheumatologists currently practicing in a conventional care model, we identified behavioral determinants of adopting an interdisciplinary model of care. To overcome barriers and strengthen enablers, sustainable funding, workforce development (IHP training), practical implementation resources (business guidance and training), and clear blueprints of successful care models and IHP roles (set-up guidance, team compositions, workflows) are required.
Background Antisynthetase syndrome (ASS) is a rare autoimmune disorder characterized by the presence of antisynthetase antibodies and variable clinical features, including myositis, arthritis, Raynaud’s phenomenon, and interstitial lung disease (ILD).[1] Among its subtypes, PL-7-associated ASS, representing approximately 3-4% of cases, is particularly associated with rapidly progressive ILD (RP-ILD) and poor prognosis.[1] Corticosteroids remain the mainstay of therapy; however, steroid-resistant disease is common, and evidence guiding optimal adjunctive immunosuppressive strategies remains limited.[2] In the absence of randomized trials, treatment is often extrapolated from other connective tissue disease-related ILDs. Data from anti-MDA5-associated ILD suggest that early, aggressive combination therapy with corticosteroids, cyclophosphamide, and tacrolimus can improve survival compared to stepwise escalation.[3] Case Report We describe a 77-year-old man with atrial fibrillation and prior stroke who presented with a 3-week history of progressive dyspnea, dry cough, and fatigue unresponsive to outpatient therapy. He had no relevant exposures but reported a 2-year history of Raynaud’s phenomenon. High-resolution CT revealed right-predominant ground-glass opacities with early fibrosis (Figure 1). Serology demonstrated high-titer anti-PL7 and anti-Ro52/TRIM21 antibodies, confirming ASS. Despite initial corticosteroids, his oxygen requirements worsened to 10 L via non-rebreather, prompting escalation to pulse methylprednisolone (250 mg IV x 3 days), cyclophosphamide (500 mg/m 2 IV monthly), and tacrolimus (target trough 5-10 ng/mL). His respiratory status improved, and by discharge, he required oxygen only with exertion. During admission, workup revealed rectal adenocarcinoma with a hepatic metastasis, for which neoadjuvant FOLFOX chemotherapy was initiated with curative intent. Cyclophosphamide was discontinued to minimize toxicity, while tacrolimus and prednisone were continued. Within 10 weeks, he no longer required supplemental oxygen. Conclusion To our knowledge, this represents the first reported case of colorectal cancer-associated anti-PL7/anti-Ro52-positive ASS presenting with rapidly progressive ILD successfully treated with early triple-agent immunosuppression. This case highlights 2 key observations: (1) early combination therapy with corticosteroids, cyclophosphamide, and tacrolimus may be lifesaving in severe, steroid-refractory anti-PL7/anti-Ro52-positive RP-ILD; and (2) The coexistence of metastatic colorectal cancer raises the possibility of a paraneoplastic variant of ASS, a rare but described phenomenon. New-onset ASS should prompt evaluation for underlying malignancy, even in amyopathic presentations. References [1.] Shi J. J Rheumatol 2017;44:1051-7. [2.] Marie I. Eur J Intern Med 2013;24:474-9. [3.] Tsuji H. Arthritis Rheumatol 2020;72:488-98.
Objectives Systemic lupus erythematosus (SLE) is frequently complicated by lupus nephritis (LN), a major cause of morbidity and renal failure.[1] Kidney transplantation improves survival and is the preferred treatment for end-stage renal disease secondary to LN.[2] While transplant-related outcomes such as graft survival are well characterized, few studies have examined the broader post-transplant course of SLE. We aimed to characterize post-transplant lupus disease activity, flare frequency, and the prevalence of major comorbidities and adverse events. Methods A retrospective chart review was conducted for patients with SLE followed at The Ottawa Hospital who underwent kidney transplantation for LN between 2006 and 2023. Demographic, clinical, and serologic data were extracted from electronic medical records. Post-transplant disease activity was assessed using the SLE Disease Activity Index (SLEDAI-2k) and cumulative damage using SLICC/ACR Damage Index (SDI). Adverse outcomes, including graft rejection, cardiovascular events, infections, metabolic complications, osteoporotic fractures, avascular necrosis, and malignancy, were recorded. Data were summarized descriptively. Results 13 female patients were identified in our cohort (13/400), with a mean age of 44.8 ± 6.2 years at transplantation and mean follow-up of 8.4 ± 5.1 years. Time spent on dialysis prior to transplantation ranged from 3 months to 13 years. Ethnic distribution of patients was 54% White, 15% Black, 15% East Asian, 8% Indigenous, and 8% Middle Eastern. Deceased kidney donor (54%) was slightly more common than living donor (46%). Most patients received prednisone (92%) and calcineurin inhibitors (85%) as part of maintenance post-transplant immunosuppression. Mean cumulative SDI was elevated at 6.2 ± 2.0 (range 3-10). SLEDAI-2k scores (n=9) ranged from 0-6 (mean 1.2 ± 2.0); most maintained remission or low disease activity, and only 1 patient experienced a lupus flare requiring treatment escalation. Post-transplant adverse outcomes included cardiovascular events (15%), new-onset diabetes (15%), and major infections (38%). Additional complications included cataracts (15%), osteoporotic fractures (15%), and avascular necrosis (8%). One patient experienced biopsy-proven graft rejection, but no malignancies or deaths were observed during the post-transplant period. Conclusion Lupus activity following kidney transplantation for LN remained quiescent, with few flares observed; however, treatment-related complications were more common. While these interim findings are based on a limited cohort, they suggest that post-transplant SLE patients tend to maintain disease control, but they demonstrate the need for ongoing monitoring of complications and organ damage from chronic prednisone use. Continued patient recruitment and longitudinal follow-up are in progress. References [1.] Hanly J. Rheumatology 2016;55;252-62. [2.] Brilland B. Kidney Int Rep 2025;10;1163-74.
Objectives Providing information to adolescents and young adults (AYA) with rheumatic diseases about the use of alcohol, recreational drugs, and reproductive health and their impact on disease and medications is critical to ensuring they can make educated decisions about their health and behaviors. We aimed to understand the informational needs of AYAs and their preferences for how (eg, websites, pamphlets, etc.), when (eg, starting age) and how frequently (eg, every visit, annually) they would like to receive this information. Methods A questionnaire co-developed with patient partners was circulated to 16-22 year olds in rheumatology clinics and by social media. Participants rated how informed they were on alcohol and recreational drug consumption, and reproductive health, as it related to their disease and medications. Responses were summarized using descriptive statistics. Respondents were then invited to participate in a virtual focus group facilitated by a Child Life Specialist and patient partner. Focus group scripts were analyzed using inductive thematic analyses. Results Of 93 survey responses, 67 completed the entire questionnaire. Most respondents were female (80.6%), 16-18 years old (55.9%) and diagnosed with JIA (67.7%). The majority felt poorly informed on how to manage symptoms after drug/alcohol consumption (68%/58%), how different types of recreational drugs/alcohol interact with medications (67%/54%), and considerations when becoming a parent (47.8%). Fewer respondents felt poorly informed about short- (37.7%/24.4%) and long- (36.2%/23.1%) term effects of recreational drug/alcohol consumption. Participants preferred informational resources were, in order, websites (70.2%), healthcare team (49.7%), pamphlets/brochures (39.2%), podcasts (27.6%) and parent/caregiver (18.5%). Focus group participants (8 females, 3 males) generally felt uninformed about how recreational drug and alcohol consumption, and reproductive health interacts with their medications and rheumatic disease (Table 1). Females preferred to receive information through social media/websites and males wanted an online collection of resources to rate and provide comments, while both valued learning from lived experiences. When asked which topics should be prioritized in educational materials, the top 3 were effects of alcohol on medications, effects of medications on reproductive health, and limits of consuming alcohol on medication and with rheumatic disease. Their preference of when and how often they wanted to receive information was age 14-16 years, with discussions occurring at every clinic visit. Table 1: Focus Group Quotes Conclusion The majority of AYA felt poorly informed about potentially harmful activities and expressed desire for more education. Preferred educational resources included social media, resource databases, and stories of lived experiences.
Objectives The use of cannabis among individuals with rheumatologic conditions has gained increasing attention due to potential effects on pain, mood, and overall quality of life. However, data on its frequency of use, motivations, and patient-reported outcomes remain limited. We compared cannabis users and non-users by sociodemographic and arthritis characteristics and HRQL, and explored motivations for use, and assessed differences in HRQL among people with rheumatic diseases. Methods Data is from the baseline visit of a pilot study of people with inflammatory rheumatic diseases who volunteered for an internet-based intervention to improve sleep. Participants self-reported cannabis use, reasons for consumption, and completed the PROMIS-29 questionnaire (physical function, anxiety, depression, fatigue, sleep disturbance, pain interference, and social participation). Characteristics were compared between cannabis users and non-users using t-test and chi-square. Associations between cannabis use, demographics, and clinical characteristics were examined using multivariable regression. Results Our sample had a mean (SD) age of 54 (14) and all were female. Most had RA or PsA, with a mean disease duration of 10 (11) years; many also had OA (30%) (Table 1). One-third reported have used cannabis in the past year, and 24% in the past 3 months (of which 38% used weekly and 31% daily/almost daily). All participations indicated they were using for medicinal reasons only (100%), with primary motivations being to improve pain (19%), sleep (17%), fatigue (<5%) or anxiety (<5%). Nearly half (46%) reported a little improvement in arthritis symptoms with use, 15% reported a lot of improvement, 31% no change, and 8% were unsure. Users reported similar levels of physical function, pain, fatigue, sleep disturbance, and social participation, but significantly higher anxiety (p=.046) and depression (p=.014) than non-users. Table 1. Sociodemographics, arthritis characteristics, and mean PROMIS-29 scores by cannabis use in the past three months Conclusion One in 3 participants in an online intervention to improve sleep reported using cannabis in the past year to improve their arthritis symptoms, with nearly a quarter using cannabis regularly to improve pain, sleep, fatigue and anxiety. Users did not report different PROMIS-29 outcomes, although 61% reported a little to a lot of symptom improvement. Understanding the motivations and health impact of cannabis use can help guide patient counseling and future research on alternative management strategies for pain and mood disorders. Supported by a CIORA grant
OBJECTIVE:Large language models (LLMs) are increasingly evaluated for rheumatology tasks, but their performance in inflammatory arthritis (IA) remains unclear. We systematically reviewed LLM performance across clinical tasks in IA. METHODS:We conducted a systematic review (PROSPERO: CRD420261359100), searching PubMed, Scopus, and PubMed Central from January 2022 to April 2026 for studies evaluating LLM performance on clinical tasks in IA. Two reviewers (YA, AG) screened 113 records. RESULTS:Eighteen studies covered rheumatoid arthritis (n = 3), axial spondyloarthritis (n = 7), psoriatic arthritis (n = 2), gout (n = 1), juvenile idiopathic arthritis (n = 1), and multiple diseases (n = 4). Most diseases and tasks were represented by only 1 to a few studies, and the evidence base remains early stage and uneven across conditions. Over 20 distinct LLMs were evaluated, including ChatGPT-3.5 to ChatGPT-4o, Gemini 2.0, DeepSeek-R1/V3, Claude, and Perplexity; ChatGPT/GPT variants were the most frequently tested models (16/18 studies), so the current evidence base is predominantly ChatGPT/GPT-based. Findings spanned patient education (n = 11), guideline adherence (n = 6), clinical reasoning (n = 3), and other applications (n = 1). All readability assessments exceeded the recommended thresholds. Guideline concordance ranged from 48% to 96%. Accuracy was lower for case-based clinical scenarios (4.24/6) than for frequently asked questions and guideline-based questions (5.32-5.36/6; P = 0.04). When compared with real clinical data, agreement was poor (Cohen and Fleiss κ ≈ 0). CONCLUSION:LLMs may support patient education, factual medication queries, and structured guideline questions when used under clinician review, but should not be used for case-based reasoning, treatment selection, or autonomous clinical decisions. None of the 18 included studies evaluated retrieval-augmented or agent-based systems, and none prospectively validated LLMs in clinical workflows. Safe integration in rheumatology will require purpose-built, knowledge-grounded systems and prospective evaluation before routine clinical use.
Background TNF Receptor Associated Periodic Syndrome (TRAPS) is a rare autosomal dominant autoinflammatory disorder. It is caused by pathogenic variants in the TNFRSF1A gene which encodes the TNF receptor 1. These mutations impair receptor shedding and disrupt TNFα signaling, leading to uncontrolled inflammation with recurrent fever, serositis, and myalgia.[1] Left untreated, chronic inflammation may result in AA amyloidosis and end-stage renal disease (ESRD). Early recognition and treatment with IL-1 inhibitors can mitigate deterioration and prevent irreversible complications such as amyloidosis. Here we present a case of TRAPS complicated by amyloidosis and associated with a novel variant in TNFRSF1A. Case Report A 48-year-old male was referred for early childhood onset, recurrent 3-5-day febrile episodes accompanied by severe abdominal pain, large joint arthralgias and myalgias. He was treated intermittently with corticosteroids and NSAIDs, with incomplete response. At 43 years old he developed chronic kidney disease with renal biopsy compatible with amyloidosis. This eventually progressed to ESRD requiring hemodialysis. Genetic testing was performed when he was 48 years old and revealed a heterozygous missense variant in TNFRSF1A (c.214_215delinsCT, p.Cys72Leu). The mutation resides in exon 3 within the extracellular cysteine-rich domain, and was predicted to disrupt disulfide bond formation, resulting in misfolded receptor protein and defective TNFα signaling. Substitutions at the same residue (Cys72Arg, Cys72Ser) had been previously demonstrated to be causative for TRAPS.[2] His asymptomatic parents did not carry the mutation. As such, this de novo Cys72Leu variant was classified as Likely Pathogenic, and the patient was diagnosed with TRAPS. Anakinra 100 mg SC daily was started which prevented further attacks. However, he remains on hemodialysis and is on the waitlist for renal transplant. Conclusion In summary, our case highlights the importance of early recognition of autoinflammatory diseases like TRAPS, in order to initiate targeted treatment and prevent life altering complications such as amyloidosis and ESRD. We report a novel variant in the TNFRSF1A gene, adding to the literature of mutations causing TRAPS. Further studies are needed to functionally characterize the biological impact of Cys72Leu, as well as to elucidate the complex mechanisms between TNF receptor dysfunction and IL-1 signaling. References [1.] Gaggiano C. Mediators Inflamm 2020;7:8562485. [2.] Lachmann HJ. Ann Rheum Dis 2014;73:2160-7.
