OBJECTIVE:Physical activity can reduce cardiovascular disease and depression risk and improve quality of life in patients with systemic lupus erythematosus (SLE). To facilitate physical activity and achieve health benefits in patients with SLE, it is critical to understand potential barriers to physical activity, including socioeconomic, social, demographic, quality-of-life, or clinical factors. METHODS:We conducted cross-sectional analyses of data from a large, diverse cohort of patients with SLE. All completed the International Physical Activity Questionnaire, recalling the past seven days of vigorous physical activity, moderate activity, or walking. Data included financial insecurity, Everyday Discrimination Scale, education, demographics, lupus-specific disease activity, immunosuppressive medication, Census Block Area Deprivation Index, and patient-reported pain, fatigue, and cognitive function. Multivariable models included logistic regression for dichotomous outcome of "any" moderate/vigorous physical activity and quasi-Poisson model for total combined days of moderate and vigorous activity. RESULTS:Of the 271 participants, 170 (63%) reported any moderate or vigorous activity in the past 7 days (mean = 2.6 days of moderate/vigorous activity). Only 4% reported zero days of physical activity. Logistic regression analysis indicated that active disease was associated with 47% lower odds of engaging in any moderate/vigorous physical activity (P = 0.04) and with a 35% reduction in the mean number of days of moderate to vigorous physical activity (P = 0.04). In contrast, individual- and area-level socioeconomic factors and patient-reported outcomes were not associated with physical activity. CONCLUSION:Moderate/vigorous physical activity was negatively associated only with disease activity. The current study reinforces the need primarily to control SLE disease activity to promote patients' ability to be physically active, which may improve symptoms.
OBJECTIVE:In the United States, axial spondyloarthritis (axSpA) diagnosis is delayed up to 14 years preventing effective management. We convened a multidisciplinary clinician and patient group to develop recommendations for rheumatology referral of adults with chronic back pain. METHODS:Systematic review (SR) and meta-analysis determined predictive values of clinical, laboratory, and imaging axSpA features for diagnosis. In a Delphi exercise, experts reviewed these test characteristics and voted to gain consensus for inclusion or exclusion in the final recommendations. Features that did not gain consensus were evaluated using discrete choice experiments (DCE). Positive likelihood ratios (+LRs) were used to calculate the probability of axSpA to develop the referral strategy. RESULTS:The SR uncovered 28 axSpA features (+LR 0.5-10). There was consensus to include uveitis, elevated erythrocyte sedimentation rate or C-reactive protein, family history of spondyloarthritis, HLA-B27, inflammatory bowel disease, sacroiliitis by imaging, good response to nonsteroidal anti-inflammatory drugs, and psoriasis. DCE allowed exclusion of features with low importance. Experts considered posttest probability of ≥33% appropriate for referral. +LRs were used to generate a scoring system to be used in adults with chronic back pain with onset before age 45 years; a score of ≥3 is considered a threshold for referral to a rheumatologist. CONCLUSIONS:On behalf of the Spondyloarthritis Research and Treatment Network (SPARTAN), we developed data-driven referral recommendations for adults with chronic back pain to a rheumatologist for evaluation of axSpA. Validation is needed to determine if axSpA is diagnosed in 33% of those referred and if this strategy reduces diagnostic delay.
OBJECTIVE:This retrospective cohort study evaluated the long-term discontinuation (LTD) of osteoporosis treatments in postmenopausal women in France and associated fracture risk and economic burden. METHODS:From the national French health care database (Système National des Données de Santé), we included postmenopausal women aged ≥60 years initiating oral bisphosphonates, intravenous bisphosphonates, or denosumab between 2012 and 2015 with three or more (bisphosphonates) or two or more (denosumab) years of continuous treatment thereafter. LTD was defined as no treatment for ≥12 months. Within each treatment cohort (intravenous bisphosphonates, oral bisphosphonates, or denosumab), propensity score matching and Cox proportional hazard regression model were used to compare fracture risk in women with versus without LTD, and mean per capita annualized (direct and indirect) costs were assessed between women with and without LTD. RESULTS:Among 81,263, 19,111, and 28,606 eligible women initiating oral bisphosphonates, intravenous bisphosphonates, and denosumab, respectively, LTD incidence was 55.1%, 68.9%, and 42.5%. LTD of oral bisphosphonates was associated with a 12% increase in fracture risk (hazard ratio [HR] 1.12 [95% confidence interval (CI) 1.06-1.19]), and LTD of denosumab was associated with a 92% increase in fracture risk (HR 1.92 [95% CI 1.75-2.08]); no significant increase was observed for intravenous bisphosphonates. LTD increased mean per capita annualized costs by €446.6 for oral bisphosphonates and €747.2 for denosumab. CONCLUSION:We observed high rates of LTD of osteoporosis treatments among postmenopausal women in France, with LTD of oral bisphosphonates increasing fracture risk by 12% and LTD of denosumab almost doubling fracture risk. These data underscore the need for careful LTD decision-making, especially for denosumab.
OBJECTIVE:Persistent pain affects around 20% of Australians after total knee replacement (TKR), yet no dedicated Australian model of care exists to address this unmet need. The Early Pain Intervention after Knee replacement (EPIK) model is being developed, informed by the effective and cost-effective UK Support and Treatment After Replacement care pathway and extensive multistakeholder engagement. Before evaluating the EPIK model of care in a randomized controlled trial, it must be adapted for the Australian context. This qualitative study aimed to explore stakeholders' perspectives to inform this adaptation. METHODS:This qualitative descriptive study, guided by a subtle realist ontologic stance and a pragmatic epistemology, used semistructured interviews with key stakeholders across Australia. A preinterview screening questionnaire captured demographic, clinical, and professional characteristics which informed purposive sampling to ensure diverse views. Interviews were audio-recorded, transcribed verbatim, and analyzed using inductive analysis. RESULTS:Sixty-one participants were interviewed (9 patients, 20 physiotherapists, 15 orthopedic surgeons, 14 general practitioners, 1 nurse, and 2 health fund managers) across all six states and the Australian Capital Territory, with 75% residing in metropolitan areas. We identified four key themes: (1) living with pain after TKR, (2) acceptability and value of EPIK, (3) defining the scope of the EPIK care coordinator, and (4) infrastructure and system-level challenges. CONCLUSION:The EPIK model was well accepted by stakeholders as the first approach designed to improve care coordination for Australians with persistent pain after TKR, with potential to support a more efficient and patient-centered health care system. These insights will inform the EPIK model, which will be tested in a registry-nested randomized controlled trial.
Rheumatology faces sustained workforce strain, widening access gaps, and escalating administrative burden. Fellowship expansion and integration of advanced practice clinicians remain essential, but existing strategies alone are unlikely to meet projected demand. Meanwhile, artificial intelligence (AI) is increasingly embedded in clinical medicine, and physically embodied, general-purpose humanoid robots have begun entering the industrial workforce. This review presents a profession-centered framework for how such humanoid systems could be trained and governed within rheumatology should they eventually enter clinical care. It is an exercise in anticipatory governance: designing oversight before deployment pressure arrives. We conceptualize humanoid systems as supervised trainee analogs within existing fellowship structures rather than as autonomous replacements for clinicians, advancing through four stages: observation and simulation, competency-based assessment, supervised patient contact, and parallel evaluation alongside fellows. Because clinically capable humanoid systems do not yet exist, each stage is paired with technology-readiness and regulatory trigger milestones, verified before activation. Oversight runs on two tracks: US Food and Drug Administration regulation governs the device, whereas fellowship-anchored training and privileging govern its local use. Proposed educational benefits, such as sharper clinical reasoning from teaching a nonhuman trainee, are framed as testable hypotheses rather than established effects. A central boundary is fixed: these systems never graduate to independent practice, and final diagnostic and therapeutic authority remains with the supervising rheumatologist. Without deliberate engagement, AI integration into rheumatology may be shaped by commercial and regulatory forces alone. Proactive stewardship, including honest acknowledgment of uncertainty, can help ensure technological change strengthens patient trust, professional standards, and workforce sustainability.
OBJECTIVE:We recently reported an immune profile that stratifies patients with axial spondyloarthritis based on clinical response to secukinumab. We now undertake an exploratory study on the secukinumab nonresponder patients to determine if immunologic changes occur during their initial secukinumab treatment that could determine their next biologic response. METHODS:At the clinician's discretion, 18 patients who did not respond to secukinumab were either switched to a tumor necrosis factor inhibitor (TNFi; n = 8) or underwent secukinumab dose escalation to 300 mg monthly or 150 mg biweekly (n = 10). Flow cytometry-derived immune cell subset frequencies and NanoString gene expression profiling of CD45RO+CD45RA-CD4+ T cells obtained during initial secukinumab treatment were stratified and reanalyzed according to subsequent treatment response based on the Bath Ankylosing Spondylitis Disease Activity Index at week 24. RESULTS:Most patients were either subsequent secukinumab responders (sSecu-Rs; n = 5/10, 50%) or subsequent TNFi responders (sTNFi-Rs; n = 6/8, 75%). During the initial secukinumab treatment, there was a significant decrease in the frequency of TH17.1 cells (P < 0.05) and interleukin-17 positive (IL17+) RORγt+ CD4+ T cells (P < 0.05) in sSecu-Rs and sTNFi-Rs, but not in patients who failed all three biologics (subsequent non responder [sNR]). Multidimensional scaling of NanoString data revealed that subsequent nonresponders (sNRs; before and after secukinumab) clustered distinctly from other groups. Following the initial secukinumab therapy, but not before it, sSecu-Rs and sTNFi-Rs showed lower expression of IL12A, IL12RB1, IFNGR1, and JAK1 compared with sNRs. CONCLUSION:Secukinumab treatment induces immunologic changes associated with reduced inflammation, even in patients who demonstrate an inadequate clinical response. Notably, patients who display these immunologic profiles are more likely to respond to subsequent biologic therapy.
Objective We evaluated real‐world treatment patterns in rheumatoid arthritis–associated interstitial lung disease (RA‐ILD) within the Veterans Health Administration (VA). Methods We performed a cohort study of RA‐ILD treatment patterns in the VA between 2006 and 2021. Patients with RA‐ILD were identified using validated administrative algorithms. Pharmacy databases were queried for medication dispensing before and after ILD diagnosis. The primary comparison was the proportion of patients prescribed each medication before and after ILD diagnosis. Multivariable Cox regression was used to evaluate predictors of initiating an American College of Rheumatology (ACR)/American College of Chest Physicians (CHEST) guideline recommended medication after ILD diagnosis among patients not using these therapies at baseline. Results Among 4,108 patients with RA‐ILD, mean age was 68.6 years and 93.4% were male. Prednisone was commonly prescribed before (64.6%) and after (76.7%) ILD diagnosis. Use of conditionally recommended first‐line therapies in the ACR/CHEST guideline (mycophenolate, azathioprine, rituximab, and cyclophosphamide) increased after ILD diagnosis, but the overall frequency was low (range 1.2% to 12.0%). Methotrexate use decreased (47.1% to 30.4%), whereas leflunomide, tumor necrosis factor inhibitors, and abatacept use increased after ILD diagnosis. Reduced forced vital capacity, anti–cyclic citrullinated peptide/rheumatoid factor seropositivity, ILD diagnosis between 2012 and 2021 (vs 2006 and 2011), and higher pulmonary visit frequency were associated with guideline recommended medication initiation while older age at RA‐ILD diagnosis, and higher comorbidity burden were associated with less frequent initiation. Conclusion Most ACR/CHEST first‐line recommended therapies for RA‐ILD treatment were infrequently used among VA patients with RA‐ILD between 2006 and 2021. These findings illustrate real‐world use of RA‐ILD therapies and suggest that treatment decisions in RA‐ILD are guided by many factors in addition to ILD severity.
OBJECTIVE:Calcinosis cutis (CC) is dystrophic calcification affecting 20% to 40% of patients with juvenile dermatomyositis (JDM). Management of CC is often challenging owing to its being refractory to usual therapeutic options. Type I interferon (IFN)-mediated immune dysregulation may be involved in the pathogenic role in CC, suggesting that altering JAK/STAT signaling through JAK inhibitors might offer a therapeutic benefit. METHODS:In this open-label, single-arm study, the primary objective was to study the effect of tofacitinib (MSN Pharmaceuticals) on the burden of CC in children (2-18 years) with JDM, as assessed by the Agatston score using a low-dose whole-body computed tomography scan at 24 ± 2 weeks follow-up. Secondary objectives were to evaluate the effect on Cutaneous Dermatomyositis Disease Area and Severity Index, Childhood Myositis and Assessment scales, steroid usage, IFNα and IFNβ levels and adverse events. Children with JDM and clinical or radiologic evidence of CC were enrolled for this study. The study drug tofacitinib was administered orally as per the standard doses based on the participant's weight band. The standard therapy included concomitant steroids, methotrexate and/or mycophenolate mofetil, and/or intravenous immunoglobulin. Those who received cyclophosphamide or rituximab in the preceding six months, were receiving concomitant topical tacrolimus, had active tuberculosis, or had hematologic abnormalities were excluded. RESULTS:Twenty children (11 boys) with a mean age of 10.4 (SD 3.6 years) completed the study. Eighteen children had CC associated with JDM, whereas two had JDM-systemic sclerosis overlap. Median duration of CC in the study population was 31 (interquartile range [IQR] 19.5-54) months. There was a significant reduction in the Agatston score, median at follow-up compared to baseline 6,349 (IQR 3,765-65,255) versus 4,007 (1,616-55,515), P = 0.012, with a moderate effect size (d-robust -0.52). No serious adverse events were noted during the study period. CONCLUSION:Tofacitinib, when added to standard therapy, reduced the Agatston score in children with CC associated with JDM. No major safety signals were observed during the study period. Clinical Trials Registry - India: CTRI/2024/02/062740.
Objective Health care transitions are a time of high needs for youth with chronic rheumatic conditions. Our study aimed to evaluate the feasibility of a multicenter randomized‐controlled trial implementing a virtual transition coach intervention (TCI) for youth transitioning from pediatric to adult rheumatology care. Methods Youth aged 17 to 18 years with pediatric‐onset rheumatic diseases were recruited from McMaster Children's Hospital in Hamilton, and Children's Hospital, London Health Sciences Centre in London, Canada. Participants were randomized to receive a youth transition roadmap (YTR) (standard of care), or YTR plus TCI—eight virtual monthly coaching sessions covering topics from the YTR. Primary outcomes included feasibility criteria, whereas secondary outcomes focused on measures of readiness for transition (Transition‐Q), global functioning (PedsQL 4.0), and self‐efficacy (PROMIS self‐efficacy for managing chronic conditions) at baseline, 8 months, and 11 months. A satisfaction survey was provided to TCI participants upon study completion. Results Of 65 patients approached, 31 (48%) consented. Over 95% of TCI sessions were attended, 80% of patients completed 8‐month follow‐up questionnaires, and missing data were 13%. TCI participants demonstrated slightly larger mean changes across each time point for each instrument compared to controls. TCI participants overwhelmingly endorsed the intervention, with 78% satisfied with the intervention and 89% willing to recommend the intervention to a friend. Conclusion Transition coaching is a feasible intervention to support youth transitioning from pediatric to adult rheumatology care. Results from this trial will inform a multicenter trial, investigating the efficacy of a TCI on transition readiness and self‐efficacy for managing chronic conditions.
OBJECTIVE:To investigate SARS-CoV-2 viral shedding duration in autoimmune patients using B cell depleting (BCD) therapy or tumor necrosis factor inhibitors (TNFi) and immunocompetent comparators. METHODS:We conducted a matched cohort analysis among participants in POSITIVES, a prospective study enrolling outpatients with acute COVID-19 within five days of diagnosis. Anterior nasal swabs were self-collected thrice weekly over two weeks and then weekly until two negative polymerase chain reaction (PCR) results. We compared autoimmune cases on BCD or TNFi at baseline with immunocompetent comparators, matched using a propensity score based on age, sex, race and ethnicity, number of COVID-19 vaccinations, calendar time, and antiviral use. Survival methods with Cox proportional hazards modeling was used to compare the time to undetectable PCR. RESULTS:We enrolled 16 BCD users and 30 TNFi users, each matched to 33 and 53 immunocompetent comparators, respectively. The most common autoimmune disease was rheumatoid arthritis (31% among BCD and 53% among TNFi). About 60% used an antiviral, and the mean number of COVID-19 vaccinations was 4.3. At the time of infection, BCD users had significantly longer viral shedding duration than comparators (median 15 vs 7 days; hazard ratio [HR] 0.43, 95% confidence interval [CI] 0.22-0.86; P = 0.017). The median time to undetectable viral load was similar between TNFi users and comparators (10 vs 8 days; HR 0.77, 95% CI 0.48-1.23; P = 0.27). CONCLUSION:BCD users had eight days longer viral shedding duration than immunocompetent comparators; TNFi users and comparators had similar viral shedding duration. These findings inform clinical and public health strategies for autoimmune patients with COVID-19.
Objective To describe patient profiles, treatment patterns, clinical outcomes, and safety of intentional dual biologic or targeted synthetic disease‐modifying antirheumatic drug (b/tsDMARD) therapy in psoriatic arthritis (PsA). A subset of patients with PsA continue to experience persistent inflammation despite b/tsDMARD monotherapy. Dual b/tsDMARD therapy has emerged as a potential strategy in refractory cases, but evidence in PsA remains limited. Methods We conducted a nested study within the International Psoriasis and Arthritis Research Team prospective cohort. Adults satisfying Classification Criteria for Psoriatic Arthritis who received two concurrent b/tsDMARDs (TNFi, IL‐17i, IL‐23i, JAKi, TYK2i, with or without apremilast) for ≥60 days were included. Baseline features, previous therapies, indications for dual therapy, and disease activity measures (tender joint count in 68 joints, swollen joint count in 66 joints, Disease Activity Index for Psoriatic Arthritis [DAPSA], Psoriasis Area and Severity Index [PASI], body surface area, patient visual analog scale) were collected. Clinical outcomes were reassessed at three‐ to six‐month intervals, with effectiveness assessed only for dual bDMARD + JAK/TYK2i combinations. Safety was evaluated through all‐cause adverse events. Results Thirty‐nine patients initiated dual therapy: 24 patients received bDMARD + JAK/TYK2i and 15 patients with bDMARD + apremilast. Patients were highly treatment‐experienced (median two conventional synthetic DMARDs and five b/tsDMARDs). Indications included refractory peripheral arthritis, concurrent joint and skin activity, palmoplantar or nail psoriasis, and persistent enthesitis. Among bDMARD + JAK/TYK2i combinations, improvements were observed in joint counts, DAPSA, PASI, and patient‐reported outcomes. Adverse events were infrequent and mild. Conclusions In this real‐world cohort, dual b/tsDMARD therapy was feasible, well‐tolerated, and associated with clinical improvement in patients with refractory PsA. These findings support its individualized use and highlight the need for controlled studies to define long‐term safety and optimal combination strategies.
Objective Our objective was to identify and describe the clinical characteristics and outcomes in patients with pre‐existing idiopathic inflammatory myopathies (IIMs) in the Veterans Health Administration (VHA) treated with immune checkpoint inhibitors (ICIs). Methods All veterans receiving ICI infusions were identified. Patients with at least two International Classification of Disease codes for IIM before first ICI infusion underwent chart review to identify patients with confirmed IIM by American College of Rheumatology/EULAR criteria. The demographics, cancer diagnoses, laboratory findings, clinical course, and mortality rates were reported. IIM cases were also reviewed to determine if patients developed IIM flare following ICI treatment. Results We identified 29,539 veterans who received at least one ICI infusion in the VHA between June 6, 2011, and February 14, 2023. The eight patients with confirmed IIM before ICI treatment were mostly White men with an average age of 71.7 years at first ICI infusion. The IIM diagnoses were dermatomyositis in three patients, polymyositis in two, antisynthetase syndrome in two, and one rheumatoid arthritis (RA)/myositis overlap. Cancer diagnoses were lung (two), melanoma (two), head and neck (two), kidney/other urinary (one), and mesothelioma (one). Diagnosis of IIM was made on average 3.1 years before ICI treatment. One patient had an IIM flare after ICI. No IIM flares were identified in other patients. Conclusion Our findings show that an IIM flare after ICI therapy can occur, but most patients did not develop a flare. These observations suggest ICIs can be considered as an option in patients with cancer with IIM with shared decision‐making and close monitoring.
Objective Rehabilitation is rarely integrated into routine rheumatology care, despite high rates of functional limitation in adults with rheumatoid arthritis (RA). The Preserving Valued Activities in Life (PREVAIL) model of care proposes a function‐focused screening survey administered during routine rheumatology visits to guide referrals to rehabilitation and facilitate integration into standard RA care. This study aimed to assess the perceived feasibility and acceptability of the PREVAIL model and inform modifications for pilot testing. Methods We used a multimethod approach including (1) a cross‐sectional survey of 309 adults with RA to assess the feasibility and validity of a proposed screening tool to identify functional limitations for referral and (2) semistructured interviews with 24 adults with RA, 6 rheumatology clinicians, and 6 physical therapists to evaluate the perceived acceptability and feasibility of the PREVAIL model of care. Results The proposed screening tool demonstrated moderate correlations with established measures of functional status and disease activity but identified 90% of participants for rehabilitation referral based on proposed disability risk criteria, necessitating refinement. Interview data revealed broad support for the PREVAIL model across key vested parties. Participants emphasized the value of proactively addressing function, identified patient and clinician knowledge gaps regarding rehabilitation, and highlighted the model's potential to enhance patient‐clinician communication. Modifications to improve feasibility included remote survey completion, educational materials for key vested parties, and an interim physical therapy consultation call to better prioritize referrals. Conclusion The PREVAIL model of care was perceived to be both feasible and acceptable. Study findings directly inform refinements to support real‐world implementation in a pilot clinical trial.
Objective The aim of this study was to explore if vitamin B3 (nicotinamide) supplementation is a safe and effective adjunctive therapy for patients with primary Raynaud phenomenon (RP) and scleroderma‐related RP. The effect of nicotinamide supplementation in human patients with RP has not been studied before. Methods Primary endpoints were to assess adherence to vitamin B3, vitamin B3‐related adverse events, and changes in the following: (1) RP frequency and severity (via the Raynaud Condition Score diary), (2) RP‐related quality of life (via the Short‐Form Assessment of Systemic Sclerosis‐Associated Raynaud's Phenomenon questionnaire), and (3) nailfold videocapillaroscopy (NVC) patterns and parameters. NVC incorporated artificial intelligence using Capillary.io software based on the validated CAPI‐Detect algorithm. We conducted a six‐week prospective longitudinal, within‐participant crossover intervention study using a three‐phase study design: A1 (baseline), B (vitamin B3 500 mg twice daily orally), and A2 (vitamin B3 washout); each phase was two weeks long. A total of 38 participants completed the study (20 with primary RP and 18 with scleroderma‐related RP). Results Vitamin B3 showed excellent adherence (98.7%) with few mild adverse events. NVC patterns improved in 45% postsupplementation (P < 0.001; total cohort), with increased normal and reduced abnormal capillaries. RP‐related quality of life and severity improvements were significant only in primary RP, persisting after washout. Conclusion Vitamin B3 was well tolerated and improved NVC patterns and parameters in both groups, with benefits persisting postwashout. Participants with primary RP had significant improvements in patient‐related outcome measures, which were not found in the scleroderma‐related RP group. Scleroderma microvasculature may be more resistant to vasodilation, possibly due to structural remodeling. Improvements during the washout phase suggest that vitamin B3 may induce functional microvascular effects beyond its pharmacological half‐life.
Objective There is growing evidence that knee osteoarthritis (OA), a significant source of chronic pain, is only partly explained by joint pathophysiology, varies significantly between individuals and may be partly driven by changes in periarticular tissues. The objective of this pilot study was to further characterize soft tissue properties that may be important to knee OA pain, and their associations with indicators of pain sensitization. Methods Forty‐two older adults (aged 50–85 years) with knee OA pain completed quantitative sensory testing (QST), myotonometry (ie, MyotonPRO) in the rectus femoris and biceps femoris, and clinical measures. Using data reduction techniques and unsupervised machine learning, we identified pain sensitivity profiles. Univariate and multivariate analyses of covariance examined associations between pain sensitivity profiles, muscle properties (stiffness, tone, decrement, relaxation time, and creep) and clinical pain, adjusted for age, sex, and body mass index. Pearson correlations assessed bivariate correlations between QST measures and muscle properties. Results Two profiles were identified: (1) high pain sensitivity or inefficient conditioned pain modulation (CPM) and (2) low pain sensitivity or efficient CPM and were significantly associated with muscle properties and clinical pain (P < 0.05), such that those with low pain sensitivity demonstrated greater tone and stiffness, and lower relaxation time and creep. Conclusion Using a brief QST battery, we identified two distinct pain sensitivity profiles that were differentially associated with periarticular tissue properties. Our results align with recent findings demonstrating distinct pain phenotypes in knee OA and that periarticular tissues may be important to understanding pain variability in knee OA.
The rapid integration of immune checkpoint inhibitors (ICIs) into standard oncology protocols has birthed a new frontier in clinical rheumatology: immune‐related adverse events (irAEs). By disrupting the programmed cell death‐1 (PD‐1)/PD‐L1 and cytotoxic T‐lymphocyte‐associated protein 4 (CTLA‐4) axes to restore antitumor T cell activity, these therapies inadvertently breach peripheral tolerance. This results in a spectrum of de novo autoimmune and inflammatory syndromes that frequently mimic established rheumatic diseases, including inflammatory arthritis and myositis. Although ICIs have revolutionized survival outcomes, the resultant irAEs pose a significant clinical challenge, affecting nearly 50% of patients and often necessitating the expertise of rheumatologists for management. This manuscript explores the unique rheumatologic phenotype of ICI‐induced toxicities, emphasizing the urgent need for a shift from broad‐spectrum glucocorticoid use toward targeted, mechanism‐driven therapies that do not compromise the abscopal antitumor effect. We review the current landscape of clinical trials investigating the repurposing of traditional disease‐modifying antirheumatic drugs and advanced biologics. Specifically, we discuss the efficacy and safety of tumor necrosis factor–alpha inhibitors, interleukin‐6 receptor antagonists, and JAK inhibitors in the context of steroid‐refractory irAEs. We further analyze the molecular commonalities between idiopathic autoimmune diseases and ICI‐induced inflammation. As the patient population receiving ICIs grows, the rheumatologist's role as a co‐manager is increasingly essential. This review highlights the need for standardized grading and treatment algorithms for rheumatologic irAEs and advocates collaborative research to separate immunotherapy toxicities from its oncological benefits.
Objective The relationship between physical activity and sleep with inflammatory arthritis (IA) is understudied, and existing research has relied largely on self‐report or short‐term assessments. The NIH All of Us database provides long‐term accelerometry data, enabling more precise estimation of the association between lifestyle behaviors and IA. Methods Participants from the All of Us database who shared electronic health record and Fitbit data were included. Daily activity and sleep metrics were compared between individuals with and without IA using multiple linear regression. Cox proportional hazards regression was used to examine the association of activity and sleep patterns with incident IA in a 10‐year follow‐up period. Results A total of 23,855 participants were included, 200 of whom had IA. Participants with IA took fewer daily steps ( P < 0.001) and had greater sleep variability ( P < 0.001) compared to those without IA. 122 individuals had incident IA. Every 1,000 extra daily steps were associated with a 7% lower risk of IA (hazard ratio [HR] 0.93 [95% confidence interval (CI) 0.87–0.99], P = 0.02). Compared to those who walked <5,000 steps daily, those who walked 5,000 to 10,000 steps and 10,000+ steps had a 41% (HR 0.59 [95% CI 0.39–0.91], P = 0.02) and 50% (HR 0.50 [95% CI 0.29–0.86], P = 0.01) reduction in risk of IA. Conclusion Individuals with IA had reduced step counts and more sleep variability compared to those without IA, highlighting how physical activity and sleep contribute to IA. Additionally, increased daily step count was associated with decreased risk of incident IA, suggesting a possible research intervention for those at high risk of IA.
