Seminars In Arthritis And Rheumatism[JOURNAL]
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200 papers
The association between residual disease and the risk of future disease flares in axial spondyloarthritis: A longitudinal study.
Renet E, Smits ML, van Tubergen A … +2 more , Vonkeman HE, Webers C
Semin Arthritis Rheum · 2026 Jun · PMID 41990461 · Publisher ↗
OBJECTIVES: To assess, in patients with axial spondyloarthritis (axSpA), whether the presence of clinically relevant signs or symptoms ('residual disease') while in an inactive disease or low disease activity (ID/LDA) st...
OBJECTIVES: To assess, in patients with axial spondyloarthritis (axSpA), whether the presence of clinically relevant signs or symptoms ('residual disease') while in an inactive disease or low disease activity (ID/LDA) state increases the risk of future disease flares. METHODS: Prospective data were used from SpA-Net, a web-based monitoring system for SpA. Residual disease was defined as the presence of ≥1 patient-experienced indicator (fatigue, back pain, and/or physical function NRS ≥4/10) or objective indicator (active peripheral manifestations, active psoriasis, elevated CRP, and/or physician global assessment NRS ≥2/10) of disease, while in ID/LDA (AxSpA Disease Activity Score [ASDAS] <2.1). A flare was defined as an ASDAS increase ≥0.9 and shift from ID/LDA to high disease activity (ASDAS ≥2.1). Multivariable logistic and Cox regression analyses investigated the association between residual disease and (time to) subsequent flares within 12 months. RESULTS: Among 135 patients (mean age 50.1 ± 13.2 years, 53 [39.3%] females), 80 (62.5%) and 60 (60.0%) had patient-experienced and objective residual disease, respectively. Thirty-four patients (25.2%) experienced a flare, after a mean of 190 (SD 97) days. In adjusted analyses, patient-experienced residual disease in those with lower education levels was associated with an increased risk of flares (OR = 17.7, 95%CI 2.1-147.5), and a shorter time-to-flare (HR = 12.1, 95%CI 1.6-91.9). Objective residual disease was not associated with the occurrence nor time-to-flare. CONCLUSION: The majority of axSpA patients in an ID/LDA state have patient-experienced or objective residual disease. Patient-experienced, but not objective, residual disease predicts flares in patients with lower education levels, suggesting prognostic relevance of residual symptoms in axSpA.
Target trial emulation of biologic and targeted synthetic disease-modifying antirheumatic drugs for rheumatoid arthritis-associated interstitial lung disease.
McDermott GC, Solomon DH, Sparks JA … +1 more , Desai RJ
Semin Arthritis Rheum · 2026 Jun · PMID 41990460 · Publisher ↗
BACKGROUND: There is limited clinical trial evidence guiding immunosuppressive medication use in patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD). We evaluated the associations between dif...
BACKGROUND: There is limited clinical trial evidence guiding immunosuppressive medication use in patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD). We evaluated the associations between different biologic and targeted synthetic DMARD (b/tsDMARD) treatments with outcomes in RA-ILD patients. METHODS: We identified RA-ILD patients using Medicare data from 2006 to 2019 and performed emulated target trials using observational data. Propensity score (PS) matched cohorts compared abatacept, janus kinase inhibitors (JAKi), IL-6 inhibitors (IL-6i), and tumor necrosis factor inhibitors (TNFi); each b/tsDMARD was compared in separate two-way comparisons to rituximab initiators using an intention-to-treat framework. The primary outcome was a composite of respiratory hospitalization, lung transplant, or death. We calculated hazard ratios using Cox proportional hazards regression. RESULTS: We analyzed RA-ILD patients initiating abatacept (n = 694), JAKi (n = 156), IL-6i (n = 389), or TNFi (n = 734), each PS-matched to an equal number of rituximab initiators. There were no statistically significant differences in the risk of the composite outcome of respiratory hospitalization, lung transplant, or death: abatacept (HR 0.87 95%CI 0.75-1.00), JAKi (HR 0.74 95%CI 0.51-1.08), IL-6i (HR 1.08 95%CI 0.88-1.33), and TNFi (HR 1.09 95%CI 0.95-1.25). In secondary analyses, abatacept (HR 0.84 95%CI 0.71-0.98) and JAKi (HR 0.62 95%CI 0.40-0.96) were associated with lower mortality compared to rituximab. CONCLUSIONS: In target trial emulations, there were no statistically significant differences between rituximab and other b/tsDMARDs for the primary composite outcome. However, abatacept and JAKi were associated with reduced mortality. Randomized controlled trials in RA-ILD are needed to determine optimal treatment.
A Delphi exercise informing the development of criteria to measure response to treatment in giant cell arteritis.
Soowamber ML, Bond M, Sanchez-Alvarez C … +25 more , Langford CA, Aydin SZ, Buttgereit F, Camellino D, Cid MC, Grayson PC, Hellmich B, Hendry A, Kermani TA, Khalidi NA, Mackie SL, Mahr A, Matteson EL, Maz M, Merkel PA, Monach PA, Neill L, Ponte C, Salvarani C, Schmidt WA, Villiger PM, Warrington KJ, Dejaco C, Ramiro S, Touma Z
Semin Arthritis Rheum · 2026 Jun · PMID 41985413 · Publisher ↗
OBJECTIVE: To identify the most important and relevant items to consider when developing criteria to measure response to treatment in giant cell arteritis (GCA). METHODS: As part of an ongoing project to develop response...
OBJECTIVE: To identify the most important and relevant items to consider when developing criteria to measure response to treatment in giant cell arteritis (GCA). METHODS: As part of an ongoing project to develop response criteria for GCA, a 4-round web-based Delphi exercise was conducted. Participants included patients with GCA and health professionals with expertise in GCA. Participants rated the importance (1=lowest, 9=highest) of 51 items selected based on a systematic literature review, grouped into six domains, and could suggest additional items. Items scored 7-9 by at least 70% of health professionals and 70% of patients were considered critically important and to have reached consensus. In the last round of the Delphi, participants ranked the top 10 most relevant items. A task force (n = 32 members) meeting followed to review the Delphi results, discuss rankings, and finalize the selection of items. RESULTS: One hundred eighty-seven physicians and 85 patients, from 38 countries, participated in the Delphi exercise. Twenty-four (75%) task force members participated in the virtual meeting. Thirteen new items were proposed in round 1. Twenty-four items were rated as critically important. No items were excluded during any round, and consensus was not reached for 40 items. The top 3 highest rated items by both patients and physicians were headache (ranked highest by 52%), amaurosis fugax (highest=10%), and jaw claudication (highest=7%). Twelve items were selected for the next phase of the project. CONCLUSION: Experts and patients identified 12 items considered important for measuring response to treatment in GCA.
Systemic sclerosis-related digital ulcers: Current understanding and updated management approaches- a primer for clinicians.
Ozen G, Domsic RT, Hughes M
Semin Arthritis Rheum · 2026 Jun · PMID 41985412 · Publisher ↗
Digital ulcers (DUs) are a common and debilitating manifestation of systemic sclerosis (SSc), driven by complex vascular dysfunction and mechanical factors, and are associated with substantial pain, disability, infection...
Digital ulcers (DUs) are a common and debilitating manifestation of systemic sclerosis (SSc), driven by complex vascular dysfunction and mechanical factors, and are associated with substantial pain, disability, infection risk, and higher burden of broader disease. Despite growing insights into the contribution of endothelial injury and impaired angiogenesis, as well as increasing use of imaging and biomarker-based assessments, SSc-related DUs remain an area of significant unmet clinical need. Management is multifaceted, encompassing wound care, vasodilator/active therapies, and selected interventional procedures. Yet major gaps persist in access to specialized care, treatment consistency, and the availability of standardized outcome measures. Continued emphasis on early detection, coordinated multidisciplinary care, and development of more effective and preventative therapies is essential to improve long-term outcomes. Here, we aim to review current knowledge on SSc-related DUs and offer an updated management framework informed by emerging studies over the past five years.
Longitudinal orientation of temporal artery biopsy for the diagnosis of giant cell arteritis: A cross-sectional study.
Loiseau P, Chatelain D, Loire R … +2 more , Schmidt J, Duhaut P
Semin Arthritis Rheum · 2026 Jun · PMID 41980318 · Publisher ↗
OBJECTIVE: To evaluate the diagnostic yield of a longitudinal temporal artery biopsy (TAB) orientation relative to a transverse orientation for the diagnosis of temporal arteritis. METHODS: Patients with giant cell arter...
OBJECTIVE: To evaluate the diagnostic yield of a longitudinal temporal artery biopsy (TAB) orientation relative to a transverse orientation for the diagnosis of temporal arteritis. METHODS: Patients with giant cell arteritis (GCA) from a multicenter prospective cohort study were included in this study. All patients included met the 1990 American College of Rheumatology classification criteria for GCA. Two independent pathologists blind to the relevant clinical data reviewed the TAB specimens. TAB positivity rates were compared between biopsy section orientations (transverse or longitudinal) with adjustment for potential confounding factors. Histological features were compared between orientations. RESULTS: This study included 337 patients with a transverse TAB section (mean age: 74.9 years, 70.6% women) and 69 patients with a longitudinal TAB section (mean age: 75.1 years, 81.4% women). After adjustment for confounding factors, longitudinal TAB section was found to be associated with a higher rate of biopsy positivity (OR: 2.93; 95% CI: 1.07 to 8.04), with 15.0% more positive TAB results. Giant cells, inflammatory cells, nerve inflammation and disruption of the internal elastic lamina were all more frequently observed on longitudinal than on transverse sections. CONCLUSIONS: This is the first study to suggest that the use of a longitudinal section for TAB results in a higher diagnostic yield than the transverse orientation.
Multimorbidity and risk of infection in patients with rheumatoid arthritis: Population-based case-control study.
You SH, Minn DK, Cha YJ … +3 more , Park SB, Song M, Jung SY
Semin Arthritis Rheum · 2026 Jun · PMID 41932225 · Full text
OBJECTIVE: Patients with rheumatoid arthritis (RA) have elevated infection risk owing to disease- and treatment-related immune dysfunction. Whether multimorbidity adds risk remains uncertain. This study evaluated the ass...
OBJECTIVE: Patients with rheumatoid arthritis (RA) have elevated infection risk owing to disease- and treatment-related immune dysfunction. Whether multimorbidity adds risk remains uncertain. This study evaluated the association between multimorbidity and infection in RA. METHODS: A nationwide nested case-control study was conducted in Korea using the Health Insurance Review and Assessment Service database mapped to the Observational Medical Outcomes Partnership Common Data Model. RA was identified by the International Classification of Diseases, 10th revision (M05-M06) with same-day disease-modifying antirheumatic drug prescriptions in 2018-2019. Patients with major immunodeficiencies or recent infections were excluded. Cases were the first serious, opportunistic, or herpes zoster infections between January 1, 2020, and April 30, 2022. Four controls were matched to each case by age, sex, and seropositivity. Multimorbidity was assessed using chronic conditions present during the 2 years preceding infection. RESULTS: Compared with patients with <10 conditions, those with RA and ≥10 conditions had higher odds of infection. A dose-response pattern was evident across multimorbidity groups. Adjusted odds ratios were 1.44 (95% confidence interval 1.32-1.58) for serious infection, 2.19 (1.06-4.53) for opportunistic infection, and 1.18 (1.05-1.34) for herpes zoster. Associations were consistent across subgroups. Multimorbidity increased nonfatal but not fatal infections. Among major infection types, only complicated skin and soft tissue infections were significant. CONCLUSION: In Korean adults with RA, multimorbidity substantially increases infection risk in a dose-response manner, particularly for cutaneous and nonfatal infections. These results highlight the cumulative impact of chronic conditions and support holistic management with proactive infection monitoring.
Lower magnitude of humoral response to recombinant herpes zoster vaccine in immunocompromised Sjögren's disease patients: evidence from a randomized double-blinded placebo-controlled trial.
Pasoto SG, Ribeiro TO, Aikawa NE … +7 more , Medeiros-Ribeiro AC, Borges BDS, Franco AS, Silveira CGT, da Silva HC, Bonfa E, da Silva CAA
Semin Arthritis Rheum · 2026 Jun · PMID 41932224 · Publisher ↗
BACKGROUND: Immunocompromised Sjögren's disease-(SjD) patients are susceptible to herpes zoster reactivated infection-(HZ/shingles), yet data on the recombinant zoster vaccine-(Shingrix®/RZV) in these patients are limite...
BACKGROUND: Immunocompromised Sjögren's disease-(SjD) patients are susceptible to herpes zoster reactivated infection-(HZ/shingles), yet data on the recombinant zoster vaccine-(Shingrix®/RZV) in these patients are limited. OBJECTIVES: To assess RZV humoral/cellular immunogenicity and safety in immunocompromised SjD patients. METHODS: Randomized double-blind placebo-controlled study comprising 67 immunocompromised SjD patients and 201 age-/sex-balanced non-immunosuppressed controls. SjD patients were randomized to receive vaccine-(SjD-V) or placebo-(SjD-P) on day-0-(D0) and D42. SjD-P were immunized after unblinding on D84 and D126. Controls were vaccinated on D0 and D42. Adverse events-(AEs) and disease activity were monitored. Humoral immunogenicity was assessed by anti-gE concentrations, with seroconversion defined as ≥4-fold increase from baseline to 6-weeks after the 2nd RZV dose. gE-specific CD4+ T cells were counted in ≅10% of participants. Vaccine impact on SjD symptoms/biological parameters was explored. RESULTS: SjD and controls were comparable regarding age [55.0 (48.3-63.8) vs. 55.0 (52.0-64.0) years; P = 0.087] and sex (P = 0.303). Seroconversion rate was lower in SjD than controls (90.6% vs. 99.5%; P < 0.001), with reduced geometric-mean-titer-(GMT) [7.1 (5.3-9.6) vs. 12.6 (11.4-13.9) mIU/mL; P < 0.001] and factor-increase-GMT [23.9 (16.0-35.8) vs. 70.4 (58.8-84.4); P < 0.001] in SjD. The cellular response was comparable between SjD patients and controls (P > 0.05). Disease activity, SjD symptoms/biological parameters remained stable (P > 0.05). No serious vaccine-related AEs occurred. CONCLUSION: RZV showed a favorable safety profile in immunocompromised SjD patients. Despite the high seroconversion rate, the response was significantly lower in magnitude compared to controls. This may compromise long-term immunity, underscoring the need for optimizing immune responses in this population (ClinicalTrials.gov-NCT05879419).
HIF-1α in Gout: A central regulator of metabolism, inflammation, and environmental stress.
Rasheed N, Reyes C, Weisman MH
Semin Arthritis Rheum · 2026 Jun · PMID 41923672 · Publisher ↗
Gout is a chronic inflammatory disease characterized by the deposition of monosodium urate crystals in the joints. However, growing research suggests a more complex pathophysiology involving genetic susceptibility, metab...
Gout is a chronic inflammatory disease characterized by the deposition of monosodium urate crystals in the joints. However, growing research suggests a more complex pathophysiology involving genetic susceptibility, metabolic stress, and environmental factors. Among emerging contributors, hypoxia-inducible factor 1 alpha (HIF-1α) has been proposed as a potential regulator that links these processes, though its role in gout remains underexplored. This review examines the emerging evidence supporting HIF-1α's role in both urate production and inflammation, to offer a unifying framework connecting these contributors to gout pathogenesis. Systemically, HIF-1α has been shown to promote a metabolic shift towards glycolysis and purine metabolism, providing a plausible mechanism for hyperuricemia. Locally, metabolic priming helps sustain immune responses, particularly through the release of interleukin-1 beta. Environmental stressors, including hypoxia and pseudohypoxia (e.g., obstructive sleep apnea), can further stabilize HIF-1α and amplify inflammatory signaling. This framework supports a model in which HIF-1α links metabolic stress, immune activation, and environmental exposures, reframing gout as a disorder of metabolic maladaptation and suggesting HIF-1α as a potential therapeutic target.
Emergency department presentations and hospital admissions for patients with biopsy-positive giant cell arteritis in South Australia.
Lyne SA, Lester S, Stanhope J … +5 more , Tieu J, Dyer KA, Shanahan EM, Ruediger CD, Hill CL
Semin Arthritis Rheum · 2026 Jun · PMID 41903314 · Publisher ↗
BACKGROUND/AIMS: Giant cell arteritis (GCA) causes significant morbidity from disease burden and treatment complications, yet Australian data on healthcare utilisation are lacking. This study quantified healthcare utilis...
BACKGROUND/AIMS: Giant cell arteritis (GCA) causes significant morbidity from disease burden and treatment complications, yet Australian data on healthcare utilisation are lacking. This study quantified healthcare utilisation among patients with biopsy-proven GCA in South Australia (SA) by examining rates and causes of hospitalisation and emergency department (ED) presentation, temporal trends, length of stay, and cumulative comorbidity burden. METHODS: Patients aged ≥50 years with positive temporal artery biopsy were identified from the SA GCA Registry (1992-2022). ED presentations and hospital admissions (2001-2022) were obtained using the SA-NT Data-linkage framework, and compared against controls (4:1) from the same sociodemographic distribution. Recurrent event Andersen-Gill time-to-event models estimated Hazard Ratios (HR). Cumulative Elixhauser comorbidity scores were determined at last visit as a surrogate for patients' overall health status. RESULTS: 435 GCA patients and 2124 controls were included. Both ED presentations and hospital admissions were increased in GCA patients compared to controls (HR 1.74 (95%CI 1.48, 2.03) and HR 1.73 (95%CI 1.14, 2.61)), with events highest within 12 months of GCA diagnosis. Mean length of stay was equivalent. GCA patients more often had a principal admission diagnosis of infection (HR 1.53, 95%CI 1.12, 2.09), cerebrovascular disease (HR 1.99, 95%CI 1.17, 3.36), osteoporosis/osteoporotic fracture (HR 4.0, 95%CI 1.06, 15.08), pulmonary embolus (HR 4.35, 95%CI 1.53, 12.27), diverticulitis (HR 4.74, 95%CI 1.12, 2.09), and atherosclerosis (HR 9.73, 95%CI 3.22, 29.4). Comorbidity index suggested no difference between GCA patients and controls (age-adjusted mean difference =-0.1, p = 0.59). CONCLUSION: This is the first Australian study to determine the significant burden of GCA, particularly in the 12 months following diagnosis. Improved understanding of healthcare utilisation will enable appropriate resource allocation and research prioritisation to improve patient outcomes.
Prognostic significance of 1-year pulmonary function changes in inflammatory myopathy-related interstitial lung disease.
Keret S, Laverde SM, Silva RL … +19 more , Choudhuri I, Gkiaouraki E, Chandra T, Pongtarakulpanit N, Bhowmick N, Kothari V, Reddy KS, Alhassan E, Aggarwal A, Almackenzie M, Sullivan DI, Faghihi-Kashani S, Yamaguchi K, Kass D, Gibson K, Ascherman DP, Moghadam-Kia S, Oddis CV, Aggarwal R
Semin Arthritis Rheum · 2026 Jun · PMID 41903313 · Publisher ↗
BACKGROUND: The prognostic value of pulmonary function test (PFT) trends in idiopathic inflammatory myopathy-related interstitial lung disease (IIM-ILD) remains unclear. We evaluated whether one-year changes in forced vi...
BACKGROUND: The prognostic value of pulmonary function test (PFT) trends in idiopathic inflammatory myopathy-related interstitial lung disease (IIM-ILD) remains unclear. We evaluated whether one-year changes in forced vital capacity (FVC) and diffusing capacity (DLCO) predict 10-year mortality and lung transplantation. METHODS: In a retrospective, single-center cohort of adults with IIM-ILD classified by autoantibody status and 2017 EULAR/ACR criteria, ILD was defined by high-resolution chest CT (HRCT). Inclusion required baseline and follow-up PFTs 6-18 months apart. Cox regression and Kaplan-Meier analyses assessed associations between PFT changes and survival. Multivariable models adjusted for age, sex, smoking, baseline FVC, and PFT timing. RESULTS: The most common IIM subset among 149 patients (mean age 50.5 ± 12.9 years, 63 % female) was anti-synthetase syndrome (73 %). Over mean 6.3-year follow-up, 41 (27.5 %) died and 6 (4.0 %) underwent transplantation. In multivariate analyses, absolute and relative FVC declines of ≥5% over one year were significantly associated with increased 10-year mortality (HR=2.78, CI 1.27-6.09, p = 0.01 and HR=2.37, CI 1.11-5.05, p = 0.025) . Larger FVC declines (≥10%/≥15 %) showed stronger mortality associations, whereas stable or improved FVC predicted better outcomes (HR=0.38, CI 0.18-0.82, p = 0.01). DLCO decline was not associated with survival. Kaplan-Meier analysis demonstrated worse survival with FVC decline≥5 % (p = 0.028). Survival did not differ by autoantibody subtype or HRCT pattern. CONCLUSION: Even modest FVC decline (≥5 %) over one year predicts mortality and transplant in IIM-ILD, while stabilization or improvement in FVC associates with improved survival and should be considered therapeutic goals. Routine FVC monitoring may support risk stratification, guide transplant referral, and serve as a trial endpoint.
Spectrum of clinical phenotypes associated with myositis-specific and myositis-associated antibodies in juvenile idiopathic inflammatory myositis: Our experience from North India.
Vignesh P, Basu S, Nadig PL … +14 more , Sivagnanaganesan S, Dod A, Kumrah R, Garg R, Khalko P, Sudhakar M, Tyagi R, Dhaliwal M, Sharma S, Pilania RK, Jindal AK, Suri D, Singh S, Rawat A
Semin Arthritis Rheum · 2026 Jun · PMID 41887030 · Publisher ↗
BACKGROUND: Myositis-specific autoantibodies (MSAs) and myositis-associated autoantibodies (MAAs) are increasingly being identified in juvenile inflammatory myositis (JIIM). The current study's objective was to character...
BACKGROUND: Myositis-specific autoantibodies (MSAs) and myositis-associated autoantibodies (MAAs) are increasingly being identified in juvenile inflammatory myositis (JIIM). The current study's objective was to characterize the incidence and clinical-phenotypic profile of MSA/MAA in a cohort of JIIM from North India. METHODS: We reviewed the medical records of the Pediatric Rheumatology Clinic of a tertiary care referral centre in Chandigarh, North India (1992 to 2024) and analysed the clinical details of children with JIIM. MSA/MAAs were assayed using a 16-antigen kit immunoblot assay (Euroline Autoimmune Inflammatory Myopathies 16 Ag, Euroimmune, Lübeck, Germany). RESULTS: Of the 173 patients of JIIM in our cohort, assay for MSA/MAA was performed in 113 patients which included juvenile dermatomyositis (n=89), clinically amyopathic dermatomyositis (n=8), overlap myositis (n=13), and juvenile polymyositis (n=3). Autoantibody positivity was seen in 72.5% (82/113; MSA =70, MAA=12) of the children, with anti-NXP2 (n=24) being the most common followed by anti-MDA5 (n=14), anti-TIF-1γ (n=12), anti-Mi 2 (n=9) in that order. Patients with NXP2 positivity were younger at onset [3.15 years; (1.2-11.88 years) p=0.015], had severe muscle weakness at onset (p=0.04) and persistent calcinosis (p=0.004) in follow-up. Patients with anti-TIF1γ antibody were observed to have persistent skin lesions (p <0.001) during follow-up. Incidence of arthritis (p=0.001), inverse Gottron papules (p=0.003), skin ulceration (p=0.065), oral ulcers (p=0.012), and ILD (p<0.001) were high in anti-MDA5-JDM. CONCLUSION: Anti-NXP2 antibody is the most common MSA noted in our North Indian cohort of JIIM. The findings emphasize the importance of region-specific data in understanding disease variability and guiding management.
Is there a window of opportunity in the treatment of giant cell arteritis with tocilizumab? Multicenter study of 471 patients.
Martín-Gutiérrez A, Loricera J, Prieto-Peña D … +8 more , Aldasoro V, Maiz O, de Miguel E, Galíndez-Agirregoikoa E, Ferraz-Amaro I, Castañeda S, Blanco R, Tocilizumab in Giant Cell Arteritis Spanish Collaborative Group
Semin Arthritis Rheum · 2026 Jun · PMID 41887029 · Publisher ↗
BACKGROUND: Tocilizumab (TCZ) is currently the first biological drug approved for the treatment of giant cell arteritis (GCA), regardless of disease stage or phenotype. The window of opportunity, a critical period for ea...
BACKGROUND: Tocilizumab (TCZ) is currently the first biological drug approved for the treatment of giant cell arteritis (GCA), regardless of disease stage or phenotype. The window of opportunity, a critical period for early intervention, is increasingly recognized in immune-mediated inflammatory disorders (IMIDs). OBJECTIVES: To assess whether there was a window of opportunity at the classic cut-off point used in clinical trials (e.g., GiACTA). PATIENTS AND METHODS: Multicenter observational study of 471 patients with GCA treated with TCZ. Patients were stratified into two groups: Newly Diagnosed (TCZ ≤6 weeks from diagnosis) and Refractory (>6 weeks). Timing effects were assessed using multivariable regression models adjusted for potential confounding factors, evaluating both the dichotomous variable "newly diagnosed GCA" and the continuous variable "time from GCA diagnosis to TCZ initiation"; multiple time cut-offs were also analyzed following the same methodological approach. RESULTS: Of the 471 patients (72.6 % female; mean age 73.5 ± 9 years), 91 (19.3 %) were classified as newly diagnosed and 380 (80.7 %) as refractory. No significant differences were observed in EULAR-defined remission, cumulative organic damage, or relapse rates after 24 months of TCZ. Using the continuous variable "time from GCA diagnosis to TCZ initiation", a significant association was observed between shorter time to TCZ initiation and EULAR remission at 24 months (OR 0.983; 95 % CI 0.967-0.999; p = 0.035), whereas no significant associations were found for organ damage or relapses. CONCLUSIONS: Although no clear window of opportunity was identified using the classic cut-off for TCZ initiation in GCA (≤6 weeks), an earlier initiation of TCZ after diagnosis appears to be associated with a higher likelihood of remission in patients with GCA.
Sex differences in patient-reported outcome measures and clinical parameters in patients with Sjögren's disease.
Kokol H, Rebel D, de Wolff L … +12 more , Oei E, van Deelen E, Ausma N, Olie L, Alberga JM, van der Vegt B, Kroese FGM, Vissink A, Delli K, Verstappen GM, Bootsma H, Arends S
Semin Arthritis Rheum · 2026 Jun · PMID 41881907 · Publisher ↗
OBJECTIVE: To explore sex differences in patient-reported outcome measures (PROMs) and clinical parameters in patients with Sjögren's disease (SjD). METHODS: Consecutive patients with clinical diagnosis of SjD, enrolled...
OBJECTIVE: To explore sex differences in patient-reported outcome measures (PROMs) and clinical parameters in patients with Sjögren's disease (SjD). METHODS: Consecutive patients with clinical diagnosis of SjD, enrolled in the prospective RESULT cohort or retrospective DiagnoSS registry, who fulfilled 2016 ACR/EULAR classification criteria, were included. PROMs evaluating sicca symptoms, fatigue, pain and health-related quality of life (HR-QoL), and clinical parameters including salivary and ocular gland function, salivary gland ultrasound (SGUS) and biopsy outcomes, physical examination results, serological parameters, systemic disease activity and damage were compared between female and male patients. RESULTS: Of the 405 SjD patients, 360 (89%) were female and 45 (11%) were male. Females had earlier onset of symptoms (median 37 vs. 51 years), longer diagnostic delay (5 vs. 3 years), scored worse on PROMs assessing sicca symptoms (e.g. ESSPRI dryness median 7 vs. 5), had lower salivary gland function (SWS, UWS; UWS<0.1ml/min: 69% vs. 44%), and more tender points than male patients. ESSDAI total score did not differ, but female patients less often had pulmonary (1.7% vs. 6.7%) and peripheral nervous system activity (3.4% vs. 11.1%) than male patients. Clinical parameters including ocular tests, SGUS (Hocevar), biopsy parameters, immunological serology and damage (SSDDI) did not differ. HR-QoL (SF-36, EQ-5D-5L: index median 0.76 vs. 0.74) and PASS (72% vs. 70%) were comparable between sexes. CONCLUSION: In this cohort of SjD patients from daily clinical practice, female and male patients showed distinct patterns of experienced symptoms and disease manifestations. The overall impact of SjD on HR-QoL was similar.
The complexity of pain in inflammatory arthropathies beyond pain intensity and impact: An OMERACT initiative.
Khot S, Cowern M, Djurtoft C … +4 more , Christensen R, Mease P, Simon LS, Choy E
Semin Arthritis Rheum · 2026 Jun · PMID 41856014 · Publisher ↗
INTRODUCTION: People with IA may suffer from pain of differing aetiologies and subtypes including nociceptive joint pain, neuropathic pain of carpal tunnel syndrome or nociplastic pain from concomitant fibromyalgia. Lack...
INTRODUCTION: People with IA may suffer from pain of differing aetiologies and subtypes including nociceptive joint pain, neuropathic pain of carpal tunnel syndrome or nociplastic pain from concomitant fibromyalgia. Lack of precise measurement tools to identify nociplastic pain influences as a contextual factor potentially all outcomes in collected clinical trials as residual pain might impact various measurements in IA. The OMERACT 2025 pain SIG discussed, developing a scoping review from protocol, to identify an instrument to measure nociplastic pain in IA and a contextualised domain definition for nociplastic pain in IA. Stakeholder opinions were sought regarding pain in IA and the importance of identifying an instrument to measure nociplastic pain in IA. METHODS: A total of twenty-four participants attending the OMERACT 2025 pain SIG session included a mix of patients, clinicians, researchers, methodologists, and industry representatives. Patient research partner (PRP), MC spoke about the impact of pain including different pain subtypes in IA. She recapped the results of OMERACT 2023 poll where participants, including PRPs, agreed that assessing different pain subtypes in IA was important to improve targeted treatments for pain. SK - a pain specialist- presented evidence supporting the presence and impact of nociplastic pain in different IA's including rheumatoid arthritis (RA), psoriatic arthritis (PsA) and axial spondylarthritis (AxSpA). Details of the scoping review protocol developed by the OMERACT Pain Working Group identifying candidate instruments for nociplastic pain assessment in IA was presented. Participants opinions were polled regarding their perspectives of the nociplastic pain definition and measurement. RESULTS: Polling showed clear agreement on advancing efforts to identify or develop an outcome measure for nociplastic pain. Most participants (86 %, 19/24) endorsed beginning with a systematic review of the existing literature to identify an appropriate validated instrument. Following a pain neuroscience education session five of the six (83 %) patient research partners (PRP) agreed they would be able to report the different pain types experienced in IA. Only one participant (1/24) agreed that the current IASP nociplastic pain definition is directly applicable to IA. Most participants (96 %) either disagreed or were uncertain, and over half (14/24) felt the definition likely requires contextualisation for IA. DISCUSSION: There was broad agreement that, in a substantial proportion of patients with inflammatory arthritis, nociplastic pain persists despite optimal treatment, is challenging to manage in routine clinical practice, and is associated with substantial patient suffering. The OMERACT meeting underscored the need for a standardized measure of nociplastic pain in inflammatory arthritis to refine eligibility criteria and support the development of stratified approaches in future clinical trials.
Increased incidence of sudden cardiac death in systemic sclerosis: data from a nationwide cohort study.
Fairley JL, Paratz E, Hansen D … +10 more , Proudman S, Sahhar J, Ngian GS, Apostolopoulos D, Walker J, Host LV, Stevens W, La Gerche A, Nikpour M, Ross L
Semin Arthritis Rheum · 2026 Jun · PMID 41833238 · Publisher ↗
OBJECTIVE: To evaluate incidence and risk factors of sudden cardiac death (SCD) in systemic sclerosis (SSc). METHODS: Individuals with SSc from the Australian Scleroderma Cohort Study meeting ACR/EULAR criteria were incl...
OBJECTIVE: To evaluate incidence and risk factors of sudden cardiac death (SCD) in systemic sclerosis (SSc). METHODS: Individuals with SSc from the Australian Scleroderma Cohort Study meeting ACR/EULAR criteria were included. International Classification of Diseases (ICD)-10 code cause of death was sourced from the Australian National Death Index. "Presumed" SCD was defined as primary cause of death being an acute cardiovascular pathology (e.g., cardiac arrest, myocardial infarction). Between-group comparisons (presumed SCD vs. overall cohort) and multivariable Cox proportional hazard modelling were used to identify SCD associations. RESULTS: Among 1708 SSc patients, 32 SCD events occurred (1.9%) over 10,650 person-years of follow-up, giving an incidence rate of 300/100,000 person-years (PY). This rate is 3-9 times higher than published community estimates (35-89/100,000PY). Participants with SCD were more likely to have a history of coronary artery disease (CAD; 40.6% vs. 13.8%, p < 0.001), reduced left ventricular ejection fraction (LVEF; 18.5% vs. 5.5%, p = 0.004) and elevated NT-proBNP (33.3% vs. 11.5%, p = 0.042). SSc heart involvement occurred in 18.8% of SCD cases and 9.4% of the remaining cohort (p = 0.074). Multivariable modelling identified that older age (hazard ratio(HR)1.15 (95% confidence interval(CI)1.10-1.20), p < 0.001), CAD (HR2.28 (95%CI1.04-5.00), p = 0.040), reduced LVEF(HR2.89 (95%CI1.06-7.90), p = 0.038) and smoking history(HR2.80 (95%CI1.21-6.49), p = 0.016) were associated with SCD. CONCLUSION: SCD occurred in 1.9% of a large SSc cohort, with an incidence rate of 300/100,000PY, representing a significant increased frequency compared to the general population. Older age, CAD, reduced LVEF and smoking history were key risk factors, highlighting important and potentially modifiable risk factors for SCD in SSc.
Phenotype-genotype correlation and treatment outcomes in mevalonate kinase deficiency: A large Turkish cohort.
Kaplan MM, Ekici Tekin Z, Kılıç Könte E … +39 more , Balık Z, Aydın T, Çağlayan Ş, Arık SD, Kurt T, Yıldız Ç, Karalı Y, Kışla Ekinci M, Çakan M, Doğantan Ş, Kılbaş G, Bozkaya Yücel B, Tanatar A, Şener S, Esen E, Öner N, Köker O, Demir S, Sağ E, Demir Yiğit Y, Baba Ö, Kaya Akça Ü, Taşkın S, Sunar Yayla EN, Yıldız M, Gezgin Yıldırım D, Paç Kısaarslan A, Kasap Demir B, Kalyoncu M, Gürgöze MK, Yüksel S, Kılıç SŞ, Bora B, Sözeri B, Aktay Ayaz N, Bilginer Y, Kasapçopur Ö, Özen S, Çelikel Acar B
Semin Arthritis Rheum · 2026 Jun · PMID 41833237 · Publisher ↗
OBJECTIVES: This study aimed to comprehensively assess the clinical spectrum, genotype-phenotype correlations, and treatment responses in a large cohort of Turkish pediatric patients with genetically confirmed mevalonate...
OBJECTIVES: This study aimed to comprehensively assess the clinical spectrum, genotype-phenotype correlations, and treatment responses in a large cohort of Turkish pediatric patients with genetically confirmed mevalonate kinase deficiency (MKD). METHODS: This retrospective, multicenter cohort study included 107 genetically confirmed MKD patients followed between 2010 and 2024 across 25 pediatric rheumatology centers in Turkey. Demographic characteristics, clinical features, laboratory parameters, genotypic data, and treatment outcomes were recorded and analyzed. RESULTS: Of the 107 patients, 48 (44.9%) were female. The median age at symptom onset was 7 (3-24) months, and the median age at diagnosis was 71 (27-115) months. The most frequent clinical features included fever in 105 (98.1%) patients, abdominal pain in 92 (86%), arthralgia in 74 (69.2%), diarrhea in 73 (68.2%), lymphadenopathy in 64 (59.8%), vomiting in 52 (48.6%), and oral aphthae in 50 (46.7%). Less frequent findings included pancreatitis in 2 (1.9%), genital aphthae in 2 (1.9%), neurosensory hearing loss in 3 (2.8%), and hidradenitis suppurativa in 1 (0.9%) patients. Amyloidosis and MAS were reported in 4 (3.7%) and 4 (3.7%) patients, respectively. Among the 107 patients, 45 (42%) had a homozygous V377I mutation (Group 1), 28 (26.2%) had a compound heterozygous mutation involving V377I and a non-V377I allele (Group 2), 15 (14%) had two non-V377I alleles (Group 3), and 19 (17.8%) had a single heterozygous mevalonate kinase gene mutation (Group 4). No statistically significant differences were observed between the groups in demographic features, attack characteristics, clinical manifestations, laboratory findings, or treatment outcomes. IL-1 antagonists were the primary therapeutic agents. Anakinra yielded no clinical response in 14 (13.1%), partial response in 17 (15.9%), and complete response in 13 (12.1%) patients. Canakinumab treatment resulted in no response in 2 (1.9%) patients, partial response in 34 (31.8%), and complete response in 56 (52.3%). CONCLUSIONS: The variability in clinical manifestations and treatment responses across genotypes highlights the complexity and heterogeneity of MKD, suggesting that factors beyond genotype may influence disease expression and therapeutic outcomes. We also confirm that heterozygous individuals may express the disease phenotype.
Trends and outcomes of lung transplant listings for connective tissue disease-associated interstitial lung disease (CTD-ILD): A 20-Year analysis from the organ procurement and transplantation network database.
Bhandari S, Bhandari S, Byers DE … +3 more , Witt C, Huecker J, Sen D
Semin Arthritis Rheum · 2026 Jun · PMID 41833236 · Publisher ↗
BACKGROUND: Lung transplantation represents a potential life-extending therapy for patients with advanced CTD-ILD. This study aims to characterize lung transplant listing outcomes among CTD-ILD patients over a 20-year pe...
BACKGROUND: Lung transplantation represents a potential life-extending therapy for patients with advanced CTD-ILD. This study aims to characterize lung transplant listing outcomes among CTD-ILD patients over a 20-year period using the Organ Procurement and Transplantation Network (OPTN) national database. METHODS: Data analyzed from the OPTN between 2003-2023 included adults ≥18 years of age with CTD-ILD listed for lung transplantation. Patients were categorized into six diagnoses: scleroderma, lupus, rheumatoid arthritis (RA), myositis, Sjögren's, and "Other" (including mixed connective tissue disease, CTD, etc.). Disease and patient specific data were obtained. Trends in listing and outcomes were analyzed in four time periods across the 20 years and among various diagnoses. We used descriptive summary statistics to characterize the sample, and univariate and multivariable logistic regression models to identify factors associated with undergoing lung transplantation. RESULTS: A total of 1977 CTD-ILD patients were listed. Scleroderma constituted the majority (47%). Listings increased fourfold (185 to 744) from the first to last time periods. Listings for all diagnoses increased with time, with rising representation of non-White patients. Trend noted towards listing patients with more advanced lung disease with time. Transplant rates rose, while wait times, and waitlist mortality declined overtime. All diseases received transplants at comparable rates. Older age, lower lung allocation scores, and male sex were associated with higher odds of transplantation, female sex with lower odds. CONCLUSION: Over two decades, CTD-ILD transplant listings have increased in volume, matched with substantially improved outcomes. This reflects the evolution of listing practices and a growing confidence in lung transplantation as a viable option for CTD-ILD.
Therapeutic effect of tofacitinib combined with leflunomide for refractory Takayasu arteritis: pilot study.
Chang S, Kong X, Ma L … +5 more , Li M, Qin J, Zhu H, Sun Y, Jiang L
Semin Arthritis Rheum · 2026 Jun · PMID 41830887 · Publisher ↗
OBJECTIVES: Takayasu arteritis (TAK) is a refractory disease with high incidence of disease relapse and glucocorticoids dependence. The objective of this study is to evaluate the effect and safety of tofacitinib (TOF) co...
OBJECTIVES: Takayasu arteritis (TAK) is a refractory disease with high incidence of disease relapse and glucocorticoids dependence. The objective of this study is to evaluate the effect and safety of tofacitinib (TOF) combined with leflunomide (LEF) treatment regimen in patients with refractory TAK, thereby providing a potential new therapeutic option for managing this condition. METHODS: Twenty-four patients with refractory TAK treated with tofacitinib and leflunomide between May 2020 to August 2024 were enrolled retrospectively from the East China Takayasu Arteritis (ECTA) cohort established by the Department of Rheumatology of Zhongshan Hospital. Most (91.7%) patients received glucocorticoids (GCs) simultaneously. Remission rate, tapering of GCs, reduction in inflammatory parameters, improvement in vascular imaging, and adverse events were analyzed in a 12-month follow-up period. RESULTS: Remission rate upon combined treatment was 87.5% (95CI: 69.0%-95.7%) at 6 months and 79.2% (95CI: 59.5%-90.8%) at 12 months respectively. Relapse rate was 8.3% (95CI: 2.3%-25.8%). GCs were successfully tapered from 15.2±12.9 mg/day at baseline to 7.8±4.5 mg/d at 6 months (p = 0.02) and 6.5±4.5 mg/day at 12 months (p = 0.001). The decrease in the erythrocyte sedimentation rate (ESR) was also significant (36.3±33.8 mm/h at baseline vs. 17.1±17.6 mm/h at 12 months, p = 0.02). Stability or improvements in imaging were observed in 5/7 (71.4%) patients who received magnetic resonance angiography (MRA) follow-up. The regimen was well-tolerated with only few and mild adverse events observed. CONCLUSIONS: The regimen of TOF combined with LEF might be a promising novel option in treating refractory TAK patients.
Suitability of the Numerical Pain Rating Scale for measuring pain in clinical trials evaluating interventions for people with shoulder disorders according to the OMERACT filter 2.2.
Furtado R, Marmura H, Haas R … +8 more , Ramiro S, Verhagen A, Whittle S, Beaton D, Shea B, Richards P, Gagnier J, Buchbinder R
Semin Arthritis Rheum · 2026 Jun · PMID 41830886 · Publisher ↗
BACKGROUND: The Outcome Measures in Rheumatology (OMERACT) group recommends pain as a core domain in clinical trials for shoulder disorders. This study evaluated the suitability of the Numerical Pain Rating Scale (NPRS)...
BACKGROUND: The Outcome Measures in Rheumatology (OMERACT) group recommends pain as a core domain in clinical trials for shoulder disorders. This study evaluated the suitability of the Numerical Pain Rating Scale (NPRS) for measuring pain using the OMERACT Filter 2.2. METHODS: Following the OMERACT Handbook for instrument selection, a systematic review assessed the NPRS's construct validity, reliability, longitudinal construct validity, clinical trial discrimination, and thresholds of meaning. Articles were independently screened, appraised with the COSMIN-OMERACT Good Methods Checklist, and rated as green (good), amber (caution), red (poor), or white (no evidence). Only green and amber studies were included. Findings were summarized in a Summary of Measurement Properties table and discussed at the 2025 OMERACT Shoulder Special Interest Group workshop. RESULTS: Twelve studies, including 18 pieces of evidence met eligibility criteria. Three studies examined construct validity, two test-retest reliability, four longitudinal construct validity, six clinical trials discrimination and three thresholds of meaning. Six (33%) components of evidence had good methods and were rated green and 12 were rated amber. There was significant heterogeneity in NPRS versions and formats evaluated across studies, questioning the validity of synthesizing the data together. Therefore, 75% of respondents at the 2025 OMERACT conference agreed that synthesizing results from studies using different NPRSs was inappropriate. CONCLUSIONS: The NPRS cannot progress to the endorsement stage for the core domain of pain for shoulder conditions due to insufficient evidence for any single NPRS version. Current evidence is insufficient to support its use to measure pain in clinical trials of shoulder disorders.
Evaluation of disease severity and treatment responses in patients with enthesitis-related arthritis.
Aydin S, Balik Z, Batu ED … +6 more , Bayindir Y, Unal D, Ercan Emreol H, Basaran O, Bilginer Y, Ozen S
Semin Arthritis Rheum · 2026 Jun · PMID 41825256 · Publisher ↗
OBJECTIVES: This study evaluated treatment responses to various drugs in patients with enthesitis-related arthritis (ERA) and assessed disease activity indices. Secondary aims included identifying factors influencing bio...
OBJECTIVES: This study evaluated treatment responses to various drugs in patients with enthesitis-related arthritis (ERA) and assessed disease activity indices. Secondary aims included identifying factors influencing biologic use and characterizing clinical features and comorbidities in a regional cohort. METHODS: We retrospectively reviewed 133 pediatric ERA patients diagnosed between January 2015 and October 2023. Clinical, laboratory, radiological, and treatment data were collected. Disease activity was assessed using JADAS, BASDAI, and JSpADA scores at baseline, month three, and latest follow-up. Statistical analyses identified factors linked to biologic use, comorbidities, and active disease. RESULTS: The cohort was mostly male (74%) with a median symptom onset age of 12.2 years. HLA-B27 positivity was 53.3%, and axial involvement occurred in 74.4%. Methotrexate was the most frequently used conventional DMARD (71%). According to JSpADA and BASDAI, 41.1% and 49.4% responded to methotrexate, while 47.2% and 58.3% responded to sulfasalazine. Patients treated with biologics had higher remission rates at month three; 60.9% received anti-TNF therapy. Axial involvement, absence of peripheral arthritis, MRI-detected osteitis, and comorbidities predicted anti-TNF use. BASDAI and JSpADA showed better correlation and responsiveness than JADAS. HLA-B27 positive patients had higher ESR and CRP and used systemic steroids more often. CONCLUSION: Although most patients improved, especially with biologics, axial involvement, early diagnosis, and comorbidities were linked to greater disease burden and need for intensive therapy. Although about half of the patients initially responded to DMARDs, a substantial proportion required biologic therapy for sustained disease control. Therefore, earlier biologic treatment may be considered in patients with poor prognostic factors. BASDAI and JSpADA may be more suitable for monitoring ERA activity. Prospective multicenter studies are needed to confirm these findings and optimize treatment.
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