Objective To determine the cumulative incidence of difficult-to-manage axial spondyloarthritis (D2M-axSpA) and treatment-refractory axSpA (TR-axSpA) in a recent-onset axSpA inception cohort, identify baseline factors and characterise long-term outcomes. Methods Patients from the French prospective DESIR (DEvenir des Spondyloarthrites Indifférenciées Récentes) cohort fulfilling the Assessment of Spondyloarthritis International Society (ASAS) 2009 criteria for axSpA and exposed to ≥1 biologic disease-modifying antirheumatic drug (bDMARD) were included. Patients with D2M-axSpA and TR-axSpA were classified according to both the ASAS definition and an extended definition adapted to historical treatment availability (failure of ≥3 b/targeted synthetic DMARDs regardless of mechanism of action). Cox proportional hazards models were used to identify baseline factors associated with D2M-axSpA. Clinical, imaging and socio-economic outcomes were analysed over up to 10 years of follow-up. Results Among 177 patients exposed to ≥1 bDMARD, the cumulative incidence of D2M-axSpA was 6.8% (95% CI 2.4 to 11.0) and 14.4% (95% CI 8.3 to 20.2) using the ASAS and extended definitions, respectively, while TR-axSpA remained rare (0.7% and 3.7%, respectively). Female sex and higher baseline disease activity were associated with the development of D2M-axSpA (extended definition). During follow-up, patients with D2M-axSpA according to the extended definition had a higher prevalence of fibromyalgia (60% vs 22.9%), greater healthcare resource utilisation (cumulative number of medical visits 110 vs 60) and opioid use (100% vs 72%). Conclusion In this recent-onset axSpA inception cohort with long-term follow-up, D2M-axSpA was rare, rarely associated with true treatment refractoriness or structural progression and was accompanied by a persistent disease burden carrying a substantial socio-economic impact, highlighting the need for a broader, patient-centred approach to its management. Trial registration number NCT01648907 .
Objective To comparatively evaluate recent adult-onset Still’s disease (AOSD) activity measures—Development and Validation of Disease Activity in AOSD (DAVID), Still’s Disease Activity Score (SDAS), Still Activity Score (SAS) with Pouchot’s Systemic Score (PSS) in an independent multicentre cohort. Methods DAVID and SDAS were modified (m) by omitting global assessments due to availability and to circumvent incorporation bias. Criterion validity was assessed by receiver operating characteristic (ROC) analysis against the treating physician’s determination of disease activity (active vs inactive). Responsiveness was evaluated by comparing mean change in scores between remission and active disease, and Cohen’s d. Longitudinal sensitivity to change was assessed using linear mixed-effects models with z-standardised scores and marginal R². Primary analysis uses imputed data, with complete-case sensitivity analysis. Results The cohort comprised 86 patients with initially active AOSD (64% female; mean age 39.4±15.0 years). In ROC analyses, mSDAS, mDAVID and SAS showed comparable area under the curves (0.69, 0.68 and 0.68, respectively), whereas PSS had a lower AUC (0.60). Responsiveness was greatest for mDAVID (Cohen’s d 0.76 (95% CI 0.30 to 1.20)), followed by mSDAS (0.61 (0.13 to 1.1)), SAS (0.46 (−0.01 to 0.90)) and PSS (0.22 (−0.30 to 0.68)). Longitudinal sensitivity to change, quantified by marginal R², was highest for mDAVID (0.65 (95% CI 0.59 to 0.70)), followed by mSDAS (0.61 (0.55 to 0.67)), PSS (0.61 (0.54 to 0.67)) and SAS (0.55 (0.45 to 0.64)). Sensitivity analyses using complete cases yielded similar results. Conclusion mDAVID and mSDAS demonstrated the most favourable and largely comparable performance profiles across the evaluated metrics, with mDAVID showing greater responsiveness and mSDAS demonstrating a stronger correlation with the articular disease domain. Trial registration number ISRCTN86135778 .
OBJECTIVES:To identify factors associated with the effectiveness and safety of Janus kinase (JAK) inhibitors in patients with rheumatoid arthritis (RA), as reflected by treatment retention. METHODS:This retrospective cohort study used data from the JAGUAR Registry, a multicentre RA registry of JAK inhibitor treatments. At 1 and 4 years, reasons and rates of treatment discontinuation were assessed. Treatment retention was evaluated using Cox regression and Kaplan-Meier curves. Factors associated with treatment retention were analysed for the discontinuation reasons of lack of effectiveness and adverse drug reactions (ADRs). RESULTS:A total of 435 treatment episodes with JAK inhibitors (tofacitinib: 118, baricitinib: 181, upadacitinib: 80, filgotinib: 56) were included. At 1 year, discontinuation rates were: 23.0% due to lack of effectiveness, 17.0% due to ADRs and 2.3% due to other reasons. At 4 years, the corresponding discontinuation rates were: 32.9%, 19.5% and 5.5%, respectively. Chronic concomitant glucocorticoid (GC) treatment was associated with JAK inhibitor discontinuation due to lack of effectiveness (p=0.007). Discontinuation rates due to lack of effectiveness were higher in patients requiring GCs for >6 months versus ≤6 months (29.1% vs 18.8% at 1 year; 50.5% vs 32.5% at 4 years). Age was associated with JAK inhibitor discontinuation due to ADRs (p=0.003). Discontinuation rates due to ADRs were higher in patients aged ≥65 years versus <65 years (25.6% vs 14.5% at 1 year; 35.3% vs 17.4% at 4 years). CONCLUSIONS:In RA, chronic concomitant GC treatment and patient age are associated with JAK inhibitor discontinuation due to lack of effectiveness and ADRs, respectively.
Objectives Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterised by synovial inflammation and joint destruction, in which fibroblast-like synoviocytes (FLS) play a pivotal role through their hyperproliferative, invasive and inflammatory properties. The salt-inducible kinase (SIK) family regulates inflammatory responses, yet the role of its isoform SIK3 in RA and the therapeutic potential of its inhibition remain unclear. This study investigates the effects of HG-9-91-01, a potent SIK inhibitor, on RA-FLS pathogenicity and disease progression. Methods The impact of HG-9-91-01 on human MH7A cells was assessed using cell counting kit-8, 5-ethynyl-2′-deoxyuridine, flow cytometry, wound healing and Transwell assays. RNA sequencing, bioinformatics analyses and western blot analysis were employed to explore the underlying mechanisms. The therapeutic efficacy of HG-9-91-01 was evaluated in a murine collagen-induced arthritis (CIA) model through clinical scoring, histopathology and micro-CT imaging. Results SIK3 was significantly upregulated in RA synovial tissues and correlated with disease activity. HG-9-91-01 potently inhibited MH7A cell proliferation, migration and invasion while promoting apoptosis. Transcriptomic and molecular analyses revealed that these effects were mediated through the concurrent suppression of the phosphoinositide 3-kinase-protein kinase B (PI3K-Akt) and nuclear factor kappa B (NF-κB) signalling pathways, leading to downstream modulation of Bcl-2-associated X protein, B-cell lymphoma 2, inducible nitric oxide synthase, tumour necrosis factor-α and matrix metalloproteinase-9. In CIA mice, HG-9-91-01 administration markedly alleviated arthritis severity, synovitis, cartilage degradation and bone erosion. Conclusions Our findings demonstrate that HG-9-91-01 attenuates RA progression by directly targeting FLS pathogenicity via dual inhibition of PI3K-Akt and NF-κB signalling, highlighting the therapeutic potential of SIK family inhibition in RA.
Objectives To determine whether baseline synovitis detected by ultrasound or MRI predicts radiographic osteoarthritis (OA) progression in the first carpometacarpal (CMC1) and interphalangeal joints.Methods We included 201 participants with hand OA from the Nor-Hand cohort. The CMC1 and interphalangeal joints were examined by ultrasound (both hands) and MRI (dominant hand) at baseline. Grey-scale synovitis, power Doppler activity and MRI-defined synovitis were scored on 0–3 scales. Bilateral hand radiographs at baseline and follow-up were scored by the same reader. We examined whether synovitis at baseline predicted radiographic progression in the same joint defined as ≥1 increase in Kellgren-Lawrence grade, osteophytes or joint space narrowing or incident erosions. CMC1 and interphalangeal joints were analysed separately using logistic regression with generalised estimating equations, adjusted for age, sex, body mass index and follow-up time.Results Radiographic Kellgren-Lawrence progression occurred in 14.7% of CMC1 joints and 10.2% of interphalangeal joints. Baseline grey-scale synovitis was associated with radiographic progression in the CMC1 and interphalangeal joints with the strongest observed association between grade 3 synovitis and Kellgren-Lawrence progression (OR (95% CI) of 9.3 (2.2 to 39.6) and 23.4 (10.4 to 52.9), respectively). Similar relationships were found for power Doppler activity and MRI-defined synovitis.Conclusions Baseline synovitis detected by ultrasound and MRI was associated with radiographic progression in both CMC1 and interphalangeal joints, supporting inflammation as a relevant prognostic feature across hand OA phenotypes.Trial registration number NCT03083548.
Objectives Guidelines for early rheumatoid arthritis (RA) recommend starting methotrexate, with optional glucocorticoid (GC) bridging, followed by treat-to-target intensifications after at least 3 months (routine care). Given RA’s heterogeneity, we evaluated a stratified treat-to-target approach (tailor-made approach) consisting of two modifications to routine care: first-line disease-modifying antirheumatic drug (DMARD) selection stratified by autoantibody status and rapid treatment intensifications guided by early treatment response (within 1 month).Methods This multicentre, open-label randomised controlled trial included adults with DMARD-naïve RA (2010 American College of Rheumatology/European Alliance of Associations for Rheumatology (EULAR) criteria) who were randomly assigned (1:1) to the tailor-made approach or routine care. Both arms followed a treat-to-target strategy, intensifying every 3–4 months until Disease Activity Score (DAS) ≤2.4. The tailor-made approach started MTX in autoantibody-positive patients and hydroxychloroquine in autoantibody-negative patients, both with intramuscular GC bridging. Additional intensifications at months 1 and 4 were allowed when DAS >2.4, 1 month after DMARD initiation or intensification, enabling treatment escalation before the standard 3-month reassessment. Routine care started MTX with GC bridging regardless of autoantibody status and without extra intensifications. The two primary outcomes were targeted synthetic/biologic (ts/b)DMARD use at 10 months and mean DAS over time; superiority required both to favour the tailor-made approach.Results In total, 308 included patients were randomised(152 tailor-made; 156 routine care). At 10 months, ts/bDMARD use was 21% in the tailor-made approach vs 17% in routine care (one-sided p=0.20). Mean DAS trajectories were similar (p=0.57). No differences were observed in mean patient-reported outcome measure trajectories or adverse events.Conclusion Modifying the standard treat-to-target strategy, by stratifying the initial DMARD according to autoantibody status combined with rapidly intensifying therapy based on early treatment response, did not result in superior clinical outcomes.Trial registration number ISRCTN16170070.
Background Rheumatoid arthritis (RA) is associated with inflammation-driven hypercoagulability and increased venous thromboembolic risk. Post hoc analyses of safety trials have raised concerns regarding a potential differential thrombotic risk with Janus kinase inhibitors (JAKi) compared with tumour necrosis factor inhibitors (TNFi). Objectives To compare viscoelastic coagulation profiles and platelet reactivity in patients with RA treated with JAKi or TNFi, and in healthy controls (HC). Methods In this single-centre observational study, patients with RA with stable JAKi or TNFi therapy (>3 months) underwent whole-blood rotational thromboelastometry (ROTEM) and impedance aggregometry (MULTIPLATE). The primary outcomes were evaluation of: (a) whole-blood thrombogenic potential and (b) platelet reactivity. Multivariable linear regression adjusted for age, body mass index, ln-transformed Simple Disease Activity Index, treatment group and ln-transformed prednisone dose. Results Sixty-one patients with RA (30 JAKi, 31 TNFi) and 34 HC were included. Compared with HC, patients with RA exhibited significantly higher maximum clot firmness (MCF) across all ROTEM assays (INTEM 63.4±4.0 vs 57.2±4.1 mm; EXTEM 66.2±4.1 vs 55.9±4.7 mm; FIBTEM 15.7±3.6 vs 12.4±3.7 mm; all p<0.001) and enhanced platelet aggregation (all p<0.001). In multivariable analyses, JAKi therapy (vs TNFi) was independently associated with higher EXTEM MCF (β=2.32, 95% CI 0.42 to 4.23; p=0.018) and FIBTEM MCF (β=1.72, 95% CI 0.07 to 3.37; p=0.041). Prednisone dose independently predicted INTEM and EXTEM MCF, while SDAI independently predicted ADP-induced aggregation (β=11.34, 95% CI 4.31 to 18.37; p=0.002). Conclusions RA is characterised by enhanced clot firmness and platelet reactivity. JAKi therapy was independently associated with higher viscoelastic clot strength compared with TNFi, while inflammatory burden and glucocorticoid exposure were key determinants of prothrombotic signatures.
Objective This systematic literature review (SLR) aims to update the evidence regarding therapeutic strategies in difficult-to-treat rheumatoid arthritis (D2T RA), building on the previous SLR informing the European Alliance of Associations for Rheumatology (EULAR) points to consider for the management of D2T RA.Methods Three research questions addressed efficacy or safety of treatments in patients with RA with (1) active disease and limited treatment options; (2) active disease with ≥2 prior biologic/targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) and (3) poor health-related quality of life and low objective disease activity (non-pharmacological interventions). MEDLINE, Embase and Cochrane Library were searched until July 2025. Meta-analysis and meta-regression were conducted.Results We screened 8589 records and included 131 studies. For research question (RQ)1, evidence on DMARD efficacy and safety was synthesised across a wide spectrum of comorbidities including obesity, cardiovascular disease, history of malignancy and respiratory comorbidities. For RQ2, all b/tsDMARDs except otilimab demonstrated better efficacy than placebo (mostly high risk of bias). Meta-regression showed efficacy was maintained for Janus kinase inhibitors (JAKi) despite increasing number of prior bDMARD failures (1 to ≥3). Safety results confirmed the increased occurrence of infection and malignancy with JAKi. For RQ3, limited evidence suggested orthopaedic surgical intervention as a potential non-pharmacological option in patients with D2T RA.Conclusions This SLR summarised evidence supporting DMARD efficacy/safety across multiple comorbidities. In patients with active RA with ≥2 prior bDMARDs, JAKi offer substantial clinical benefits but require careful risk stratification given cardiovascular and malignancy risks. Furthermore, standardised reporting and dedicated studies on non-pharmacological interventions are urgently needed.PROSPERO registration number CRD42024593584.
Objective To test whether ultrasonography of patients with rheumatoid arthritis (RA) in the American College of Rheumatology/the European Alliance of Associations for Rheumatology (ACR/EULAR) remission is useful for prediction of relapse after discontinuation of a biological disease-modifying antirheumatic drug (bDMARD). Methods Prospective trial including patients with RA in persistent ACR/EULAR remission treated with conventional synthetic DMARDs plus bDMARDs. After stopping the bDMARD, nine study visits including clinical examination and ultrasound of 14 joints (blinded to clinical data) were conducted within 52 weeks. The primary hypothesis was that a Power Doppler (PD) score≥1 predicted relapse occurring within week 16 after bDMARD cessation. Relapse was defined as a change from remission to moderate/high disease activity according to the Simplified Disease Activity Score. Results Inclusion of 110 patients was originally planned; however, the study was terminated after reaching 38 (34.5%) patients due to insufficient recruitment. Relapses till week 16 were numerically more common in patients with PD score≥1 at baseline than in those with PD=0 (9/30 (30.0%) vs 0/7 (0%), p=0.160). Similar observations were made for weeks 24 and 52. PD scores were higher at the time of relapse than at preceding visits (mean PD score difference: 3.2 (±4.5) points, p=0.034). There were trends towards a higher baseline PD score in patients who had a relapse until week 16 as compared with those who remained in remission (5.2±5.8 vs 2.3±3.0, p=0.079). Conclusion The primary endpoint was not reached. The presented data should be interpreted as hypothesis-generating, serving to stimulate future research on the value of ultrasound in assessing remission and predicting relapse in RA. Trial registration number NCT01602302 .
OBJECTIVE:To compare the effectiveness and safety of interleukin 6 receptor inhibitors (IL-6Ris) and conventional synthetic immunomodulators (csIM) in patients with polymyalgia rheumatica (PMR) who received glucocorticoids (GC) and initiated a new therapy for PMR. METHODS:We evaluated the effectiveness and safety of IL-6Ris in a retrospective comparative cohort created from the US Medicare fee-for-service medical and part D prescription claims data. Patients with PMR, on GC, without prior IL-6Ri exposure and initiating IL-6Ri/csIM therapy were identified. These patients were categorised into csIM-naïve and csIM-experienced cohorts and matched using direct methods and propensity score methods. Primary endpoints were time-to-GC discontinuation and time-to-minimal GC use (≤2 mg/day or stop GC) through year 1. Incidence rates (IRs) for adverse events of special interest were reported for IL-6Ri and csIM initiators through year 2. RESULTS:We included 415 matched treatment pairs (187/228, csIM-naïve/csIM-experienced). IL-6Ri initiators were more likely to discontinue GC (adjusted HR (aHR) 1.28, 95% CI 1.02 to 1.60; p=0.031) or achieve minimal GC use (aHR 1.28, 95% CI 1.03 to 1.58; p=0.025) by year 1 versus csIM initiators. At year 1, IR (95% CI)/100 patient-years for primary hospitalised infections was higher for IL-6Ri initiators versus csIM initiators (12.2 (95% CI 8.9 to 16.3) vs 5.7 (95% CI 3.6 to 8.6)); however, it was similar for year 2 (5.8 (95% CI 3.3 to 9.6) vs 6.4 (95% CI 3.8 to 10.1)). For other events of interest, the IRs were low and comparable in both groups. CONCLUSIONS:IL-6Ri therapy was more effective as a steroid-sparing agent than csIM for PMR with no new safety findings.
Background In the American College of Rheumatology/European Alliance of Rheumatology Associations 2010 classification criteria for rheumatoid arthritis (RA), rheumatoid factor (RF) and anti-citrullinated protein/peptide antibodies (ACPA) are assigned the same weight, although ACPA have proven more specific than RF. We aimed to refine the serological weight factors for RA classification.Materials and methods Diagnostic samples from 398 patients with RA and 448 diseased controls (DC) were evaluated with RF and ACPA assays from five different manufacturers. A grid search was conducted across all possible integer score pairs for RF and ACPA to identify the weighting combination that optimised the specificity of RA classification. This combination was applied in a refined scoring system (RSS) for three confirmatory cohorts comprising, respectively, 67, 157 and 132 patients with RA and 441, 153 and 193 DC.Findings In the investigative cohort, the optimal combination of weighting scores was characterised by higher scores for ACPA, higher antibody levels and double RF/ACPA positivity.Applying the optimal combination of weighting scores decreased misclassification compared with the 2010 RA classification criteria, minimally affecting sensitivity. For seropositive patients, RSS significantly lowered misclassification from 38.3–55.8% to 15.0–26.9%.The improved specificity of RSS (compared with the 2010 criteria) was validated in the confirmatory cohorts. Considering only seropositive patients, the RSS significantly decreased RA misclassification (8.6–36.8% vs 20.0–78.9%), minimally affecting the sensitivity (86.7–97.3% vs 86.7–96.0%).Interpretation Serological weight factors for RA classification can be improved by taking into account the antibody type, the antibody levels and single or combined positivity. The application of an RSS reduced the number of RA misclassifications.
OBJECTIVES:Medication adherence is a key determinant of treatment effectiveness in chronic inflammatory diseases but data in Behçet's syndrome (BS) remain limited. This study evaluated medication adherence in a real-world cohort of patients with BS and explored demographic and clinical factors associated with reduced adherence. METHODS:We conducted a monocentric cross-sectional study including 125 patients with BS followed at a tertiary referral centre. Adherence was assessed using the validated 8-item Morisky Medication Adherence Scale (MMAS-8). Patients were classified as having high (score=8), intermediate (score 6-<8) or low adherence (score<6). Disease activity was evaluated using the Behçet's Disease Current Activity Form and the Behçet's Disease Activity Index. Associations between adherence and clinical variables were analysed using Spearman correlation and non-parametric tests. RESULTS:The mean MMAS-8 Score was 6.82±1.32. High adherence was observed in 29.6% of patients, intermediate adherence in 48.8% and low adherence in 21.6%. Lower adherence was more frequent among patients in the lower age quartiles. No significant associations were observed between adherence and sex, disease duration, disease activity indices or treatment class. CONCLUSION:Medication adherence in BS appeared generally satisfactory, although a relevant proportion of patients reported suboptimal adherence. These findings confirm, in a BS-specific real-world setting, previously reported associations between age and medication adherence observed in chronic diseases. Routine adherence assessment may help identify patients at higher risk of poor treatment compliance and support personalised management strategies.
Background Consensus guidelines for malignancy screening in idiopathic inflammatory myopathy (IIM) were recently published by the International Myositis Assessment and Clinical Studies (IMACS) working group. This international multicentre study audited historical cancer screening practices against IMACS recommendations and examined the distribution of observed malignancies across IMACS-defined risk categories in a real-world cohort.Methods This retrospective study included patients with IIM from eight centres across seven countries/regions. Patients were stratified using IMACS-defined cancer risk categories. Historical screening was compared with the guideline recommendations. Multivariable logistic regression identified predictors of cancer and underscreening.Results Of the 795 patients (72.3% female), 51.7%, 37.9% and 10.4% were classified as high risk, moderate risk and standard risk, respectively. Across all sites, few high-risk (6.2%), moderate-risk (2.7%) and standard-risk (11.1%) patients underwent a full panel of IMACS-recommended tests. Within 3 years of diagnosis, 86 patients (10.8%) developed malignancy. Among observed cancers, 77.4% occurred in high-risk and 22.6% in moderate-risk patients, with none detected in the standard-risk group. Anti-transcription intermediary factor 1-gamma (TIF1γ) positivity (OR 4.64, 95% CI 2.35 to 9.16, p<0.001), smoking (OR 3.00, 95% CI 1.64 to 5.50, p<0.001), night sweats (OR 12.76, 95% CI 2.72 to 59.87, p=0.001) and increasing age (OR 1.05 95% CI 1.03 to 1.07 per year, p<0.001) were independently associated with cancer, whereas anti-Mi2 antibodies and non-dermatomyositis subtypes were protective. Cancer risk increased with each additional high-risk feature (OR 1.70) and decreased with each low-risk feature (OR 0.76). Underscreened individuals had lower rates of immune-mediated necrotising myopathy (5.6% vs 14.3%, p=0.005) and anti-TIF1γ positivity (6.8% vs 31.4%, p<0.001).Conclusion Observed cancer distribution across IMACS risk categories was consistent with the framework’s stratification logic, but differential screening intensity precludes formal assessment of predictive validity. Variation between historical practice and current recommendations underscores the need for continued education and prospective longitudinal studies to assess cumulative risk, age thresholds, screening uptake and outcomes in real-world clinical settings.
Since 1975, the Resnick and Niwayama classification criteria have served as the standard framework for defining diffuse idiopathic skeletal hyperostosis (DISH) in research. These criteria predominantly identify advanced disease. Accumulating evidence towards an updated definition of DISH is warranted. In this review we aimed to re-evaluate the definition of DISH in light of contemporary evidence and identify elements that may inform future classification criteria.A literature review was conducted of studies published between 1975 and 2025. Data extraction targeted imaging features, including site-specific bone formation and pre-DISH characteristics, as well as clinical features, functional outcomes and available markers. Findings were qualitatively synthesised.119 studies were included. Imaging data indicated that degenerative spinal disease alone is insufficient to exclude DISH. Bony bridges most commonly affect the thoracic spine, though involvement of the cervical and lumbar regions is well documented. Disease progression is typically slow, and frequent entheseal involvement of pelvic, chest wall and peripheral sites. Epidemiological data demonstrate a rising prevalence with age and a male predominance. DISH shows strong association with metabolic syndrome, type 2 diabetes, elevated body mass index, raised systolic blood pressure, dyslipidaemia, hyperuricaemia and cardiovascular disease. Inflammatory markers are generally within normal ranges. Evidence regarding physical impairment remains mixed, with some studies reporting reduction in spinal mobility and chest expansion alongside broader functional limitations.This review moves beyond the Resnick and Niwayama criteria to offer an updated framework to support the development of future DISH classification criteria, particularly to earlier disease stages.
Objective Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are increasingly recognised for benefits beyond glycaemic control, including anti-inflammatory, anti-atherogenic and potential immunomodulatory effects. Given the high burden of metabolic dysfunction, accelerated cardiovascular disease and chronic systemic inflammation in systemic lupus erythematosus (SLE), significant interest has emerged regarding their therapeutic role in this population.Methods We conducted a Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-guided scoping review of PubMed, Embase, Scopus and the Cochrane Library from database inception to April 2026, including peer-reviewed clinical studies, case series, case reports and relevant research evaluating GLP-1 RAs in SLE while excluding conference abstracts and unpublished material.Results Fourteen studies were included, comprising narrative reviews, mechanistic analyses, editorials and case reports. Across these studies, GLP-1 RAs demonstrated consistent anti-inflammatory, metabolic and endothelial effects relevant to SLE, with mechanistic data suggesting reductions in cytokine signalling, oxidative stress and macrophage activation. Current evidence specific to SLE is largely derived from small observational cohorts, retrospective analyses and isolated case reports, while much of the supportive anti-inflammatory and immunomodulatory data originate from preclinical studies or extrapolated from the broader rheumatic disease populations. GLP-1 RAs appear to have an acceptable safety profile in autoimmune populations, although drug-induced lupus was reported in two case studies.Conclusion Collectively, findings from the included studies suggest that GLP-1 RAs may provide metabolic and anti-inflammatory benefits in SLE with an acceptable safety profile; however, clinical data specific to SLE remain limited and large high-quality prospective clinical trials are required to refine therapeutic indications, optimal patient selection and immunological effects.
BACKGROUND:Whether primary aldosteronism (PA), the most common endocrine cause of hypertension (HTN), contributes to HTN and cardiovascular disease burden in systemic sclerosis (SSc) has never been explored. We aimed to assess the prevalence and management of HTN, prevalence of positive PA screening test results and the associations between markers of PA with HTN and SSc-related outcomes in SSc. METHODS:Data from adult SSc patients and normotensive healthy controls (HC) were analysed in this single-centre study. HTN was defined as blood pressures ≥140/90 mm Hg on two visits or as documented in medical records. PA screening was performed using the aldosterone:renin ratio (ARR). Associations between biomarkers of PA (renin, aldosterone, ARR, hybrid steroid 18-hydroxycortisol (18OHF)) with HTN and SSc-related outcomes were assessed using multivariable regression modelling. RESULTS:Data from 112 SSc patients (median (IQR) age 60 (49, 69) years, 79% female) and 48 HC (median (IQR) age 42.5 (31, 57) years, 52% female) were analysed. At baseline, 41 SSc patients (37%) had HTN, increasing to 52% of the cohort at the last follow-up visit (median follow-up 5.1 years). The prevalence of positive baseline ARR in SSc was 8% (9/112), corresponding to 12% (5/41) in the hypertensive subset. No associations were observed between biomarkers of PA and SSc-related renal and cardiovascular outcomes or HTN at last follow-up visit. CONCLUSIONS:HTN was common in this SSc cohort, and prevalence of positive PA screening test was estimated at 12% among hypertensive SSc patients, supporting consideration of PA screening in this population.
OBJECTIVE:Women with immune-mediated inflammatory diseases (IMID) are at increased risk of cervical cancer. We aimed to determine the prevalence of carcinogenic high-risk human papillomavirus (HR-HPV) infection and identify factors associated with infection in women with IMID. METHODS:We conducted a prospective, single-centre study at a French university hospital. We assessed compliance with cervical cancer screening (CCS) recommendations among all patients aged 30-65 years who attended follow-up visits between March 2024 and May 2025. HPV screening with vaginal self-sampling (VSS) was offered to all women not up to date with CCS. The primary outcome was HR-HPV infection prevalence. RESULTS:Among the 485 patients eligible for CCS, 296 were not up to date with CCS and were therefore eligible for VSS. Of these, 276 (mean age: 48±10 years) consented to participate and were included in the study. HR-HPV was detected in 55 patients (20%, n=55/276), among whom 35% (n=19/55) harboured multiple HR-HPV infections (≥2 types). In multivariable analysis, age at first sexual intercourse (OR (95% CI) 0.85 (0.73 to 0.96)) and number of lifetime sexual partners (OR 1.19 (1.05 to 1.38)) were associated with HR-HPV infection. In exploratory multivariable analyses, longer duration of biological therapy was associated with multiple HR-HPV infections (OR 1.57 (0.99 to 2.85)). CONCLUSIONS:The prevalence of HR-HPV infection in patients with IMID who are not up to date with CCS is 20%. Behavioural factors were associated with HR-HPV infection, while treatment-related findings regarding multiple HR-HPV infections were exploratory and warrant confirmation in larger prospective studies. TRIAL REGISTRATION NUMBER:NCT06302725.
Objectives To investigate the impact of vitamin D on disease activity, function and health in patients with radiographic axial spondyloarthritis (r-axSpA) undergoing biological disease-modifying antirheumatic drug (bDMARD) therapy.Methods Patients with r-axSpA and active disease at baseline initiating a bDMARD were included in this analysis. Vitamin D (25-hydroxyvitamin D) was measured at baseline and every 6 months until year 2; deficiency was defined as <20 ng/mL. The outcomes were AxSpA Disease Activity Score (ASDAS), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Patient Global Assessment (PGA), Bath Ankylosing Spondylitis Functional Index (BASFI), Assessment of SpondyloArthritis international Society Health Index (ASAS-HI) and C reactive protein (CRP). Longitudinal associations were evaluated using generalised estimating equations, with sensitivity analyses accounting for time-varying confounders.Results We analysed 122 patients (mean age 36.6 (10.3) years; 66.4% male), of whom 53.3% had vitamin D deficiency at baseline. In longitudinal models, normal vitamin D levels were associated with lower ASDAS (β per 1 ng/mL increase: −0.010; 95% CI −0.017 to −0.003), BASDAI (β: −0.021; 95% CI −0.036 to −0.006), PGA (β: −0.021; 95% CI −0.039 to −0.003) and BASFI (β: −0.015; 95% CI −0.032 to 0.001). Effect estimates of ASDAS, BASDAI, BASFI, CRP (and their corresponding categorical outcomes) were attenuated in sensitivity analyses but remained directionally consistent. Positive associations with PGA and ASAS-HI were also observed though the estimates were not consistent through all models.Conclusions Normal vitamin D levels were modestly associated with lower disease activity in r-axSpA treated with bDMARDs. Monitoring and optimising vitamin D status may support better disease control.
Systemic sclerosis (SSc) is a rare, heterogeneous, systemic autoimmune rheumatic disease characterised by vasculopathy, immune dysregulation and fibrosis affecting multiple organ systems. The complexity and variability of SSc manifestations pose significant challenges for clinical trial design and endpoint selection. Historically, three types of trial concepts have emerged: studies focused on a single organ; studies suggesting disease modification by combining a primary single-organ endpoint with supportive secondary endpoints across other systems, and studies explicitly designed to demonstrate disease modification through combined endpoints.This expert review explores the current landscape and future directions of clinical endpoints in SSc trials. It highlights the growing importance of patient-reported outcomes, such as the Health Assessment Questionnaire-Disability Index and ScleroID, which provide valuable insights into patient experiences. The review also discusses the emergence of candidate composite endpoints, including the revised Composite Response Index in Systemic Sclerosis, which integrates clinical, functional and patient-centred measures to better reflect treatment efficacy.Despite progress, significant unmet needs remain. Many endpoints assess damage at advanced stages, underscoring the need for earlier indicators of disease progression. The review advocates for incorporating time-to-event analyses, imaging and biomarker-based assessments to enhance sensitivity and relevance. It also emphasises the importance of refining composite endpoints to include continuous measures and broader domains such as vascular and gastrointestinal involvement. These efforts aim to improve the design and interpretability of SSc clinical trials, ultimately enhancing therapeutic development and patient outcomes.
