RMD Open最新文献

{"title":"Incidence, baseline-associated factors and burden of difficult-to-manage axial spondyloarthritis: a 10-year analysis of the DESIR cohort.","authors":"Olivier Fakih, Anna Moltó, Frank Verhoeven, Clément Prati, Daniel Wendling","doi":"10.1136/rmdopen-2026-007094","DOIUrl":"10.1136/rmdopen-2026-007094","url":null,"abstract":"<p><strong>Objective: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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%).</p><p><strong>Conclusion: </strong>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.</p><p><strong>Trial registration number: </strong>NCT01648907.</p>","PeriodicalId":21396,"journal":{"name":"RMD Open","volume":"12 3","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13560959/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148906747","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative evaluation of disease activity measures for adult-onset Still's disease: a multicentre, retrospective, cohort study.","authors":"Stefan Vordenbäumen, Tim Filla, Rhea Friedrich, Norbert Blank, Diana Ernst, Jörg Henes, Gernot Keyßer, Philipp Klemm, Martin Krusche, Anna Meinecke, Jürgen Rech, Nils Schulz, Simon Michael Petzinna, Anne Pankow, Valentin S Schäfer, Alexander Pfeil, Sebastian Klapa, Georg Pongratz, Eugen Feist, Anna Kernder","doi":"10.1136/rmdopen-2026-007112","DOIUrl":"10.1136/rmdopen-2026-007112","url":null,"abstract":"<p><strong>Objective: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p><p><strong>Trial registration number: </strong>ISRCTN86135778.</p>","PeriodicalId":21396,"journal":{"name":"RMD Open","volume":"12 3","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13548246/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148892278","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Factors associated with the effectiveness and safety of Janus kinase inhibitors in rheumatoid arthritis: an 8-year observational study from the JAGUAR Registry.","authors":"Cristina Martinez-Molina, Beatriz Frade-Sosa, Cesar Diaz-Torné, Raimon Sanmarti, Hèctor Corominas","doi":"10.1136/rmdopen-2026-007099","DOIUrl":"10.1136/rmdopen-2026-007099","url":null,"abstract":"<p><strong>Objectives: </strong>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.</p><p><strong>Methods: </strong>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).</p><p><strong>Results: </strong>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).</p><p><strong>Conclusions: </strong>In RA, chronic concomitant GC treatment and patient age are associated with JAK inhibitor discontinuation due to lack of effectiveness and ADRs, respectively.</p>","PeriodicalId":21396,"journal":{"name":"RMD Open","volume":"12 3","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13536016/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148866668","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and safety of upadacitinib in patients with psoriatic arthritis and exposure to one anti-TNF: post hoc analysis of SELECT-PsA 2.","authors":"Laura C Coates, Philip Mease, Arthur Kavanaugh, Joseph F Merola, Marina Magrey, Thomas Iyile, Limei Zhou, Lucia Novelli, Ivan Lagunes, Arathi R Setty, Filip Van den Bosch","doi":"10.1136/rmdopen-2025-006655","DOIUrl":"10.1136/rmdopen-2025-006655","url":null,"abstract":"<p><strong>Objective: </strong>This post hoc analysis of the SELECT-PsA 2 study evaluated long-term efficacy and safety of upadacitinib 15 mg once daily in patients with psoriatic arthritis (PsA) and exposure to one prior tumour necrosis factor inhibitor (TNFi).</p><p><strong>Methods: </strong>Patients were randomised to upadacitinib 15 mg once daily or placebo (switched to upadacitinib at week 24). Efficacy assessments 20%/50%/70% improvement in American College of Rheumatology response criteria (ACR20/50/70), minimal disease activity (MDA), 75%/90% improvement in Psoriasis Area Severity Index Score (PASI75/90), pain) were conducted through 152 weeks. Analyses evaluated the impact of prior TNFi exposure duration, skin improvement by location and early pain response as a predictor of long-term MDA. Safety was reported as treatment-emergent adverse events through week 152.</p><p><strong>Results: </strong>Of 195 patients with exposure to one prior TNFi, 90 and 105 were randomised to upadacitinib 15 mg once daily and placebo, respectively. More patients randomised to upadacitinib 15 mg once daily versus placebo achieved ACR20 (57.8% vs 21.9%), ACR50 (37.8% vs 9.5%), ACR70 (22.2% vs 0%) and MDA (24.4% vs 2.9%) at week 24. Responses were maintained or improved through week 152. Patients who switched from placebo at week 24 achieved sustained PASI75/90 responses across different anatomical regions. Efficacy was generally similar regardless of the duration of prior TNFi exposure in sensitivity and tertile analyses. Lower pain scores at weeks 2 and 12 predicted MDA achievement at week 152. No new safety signals were identified.</p><p><strong>Conclusion: </strong>Upadacitinib 15 mg once daily demonstrated sustained efficacy and an acceptable safety profile in patients with PsA and exposure to one prior TNFi, irrespective of the duration of previous TNFi exposure.</p>","PeriodicalId":21396,"journal":{"name":"RMD Open","volume":"12 3","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13536139/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148840674","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolic effects of GLP-1 receptor agonists in rheumatology patients and inflammatory outcomes: a single-centre retrospective cohort.","authors":"Miriam Retuerto-Guerrero, Ignacio González Fernández, Mirian Alejo Ramos, Ismael González Fernández, Andrea Vélez Blanco, Anibal Martin Sanz, Octavio Miguel Rivero-Lezcano, Elvira Díez-Álvarez","doi":"10.1136/rmdopen-2026-007122","DOIUrl":"10.1136/rmdopen-2026-007122","url":null,"abstract":"<p><strong>Background: </strong>Obesity and type 2 diabetes are common in rheumatology, often exacerbated by glucocorticoids. Real-world data on glucagon-like peptide-1 receptor agonists (GLP-1RAs) in this setting remain limited.</p><p><strong>Objectives: </strong>To evaluate the metabolic effectiveness and safety of GLP-1RAs in rheumatology outpatients, including inflammatory marker and subgroup analyses.</p><p><strong>Methods: </strong>Single-centre retrospective study (October 2024-October 2025) including 119 patients (from 169 screened) treated with GLP-1RAs. Paired analyses were performed at 3, 6 and 12 months. Exploratory comparisons included participants with chronic inflammatory arthritis (n=46) and those with non-inflammatory disease (n=43).</p><p><strong>Results: </strong>Patients had high baseline cardiometabolic burden (mean body mass index (BMI) 34.9±9.9 kg/m²; diabetes 96.6%). GLP-1RA initiation was associated with sustained weight loss: -4.0 kg, -4.5 kg and -7.7 kg at 3, 6 and 12 months (all p<0.001; -8.2% at 12 months), with 56.5% improving ≥1 BMI category. Haemoglobin A1c decreased by -0.97%, -0.69% and -0.91% (all p<0.001), alongside significant reductions in fasting glucose (up to -24.8 mg/dL; p<0.001). Lipid improvements included reductions in low-density lipoprotein-cholesterol (-12.2 mg/dL; p=0.006) and triglycerides (-21.7 mg/dL; p=0.007). At 12 months, erythrocyte sedimentation rate decreased significantly (p=0.023), while CRP showed a non-significant decline (p=0.076); both were significantly reduced in the inflammatory subgroup. No significant differences were observed between inflammatory and non-inflammatory groups in adjusted metabolic trajectories. Adverse events were mainly gastrointestinal (13.4%); pancreatitis (0.8%) and cholecystitis (1.7%) were rare. Discontinuation occurred in 6.7%. One death (mesenteric ischaemia) had unclear causality.</p><p><strong>Conclusions: </strong>GLP-1RAs were associated with meaningful metabolic improvements in patients with rheumatic diseases, with a favourable safety profile. Potential anti-inflammatory effects require confirmation in prospective studies.</p>","PeriodicalId":21396,"journal":{"name":"RMD Open","volume":"12 3","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13536120/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148819482","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Associations between synovitis and radiographic osteoarthritis progression in the first carpometacarpal and interphalangeal joints: results from the Nor-Hand study.","authors":"Lovisa Klingenberg, Ida K Haugen, Hilde Berner Hammer, Øystein Maugesten, Alexander Mathiessen, Marthe Gløersen","doi":"10.1136/rmdopen-2026-007074","DOIUrl":"10.1136/rmdopen-2026-007074","url":null,"abstract":"<p><strong>Objectives: </strong>To determine whether baseline synovitis detected by ultrasound or MRI predicts radiographic osteoarthritis (OA) progression in the first carpometacarpal (CMC1) and interphalangeal joints.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p><p><strong>Trial registration number: </strong>NCT03083548.</p>","PeriodicalId":21396,"journal":{"name":"RMD Open","volume":"12 3","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13504491/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148797719","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SIK inhibitor HG-9-91-01 suppresses the pathogenic activity of fibroblast-like synoviocytes in rheumatoid arthritis.","authors":"Xiaohao Wang, Yuanyuan Li, Hanchao Li, Lingfei Mo, Xinyi Liu, Zechao Qu, Jing Wang, Liang Yan","doi":"10.1136/rmdopen-2026-007000","DOIUrl":"10.1136/rmdopen-2026-007000","url":null,"abstract":"<p><strong>Objectives: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":21396,"journal":{"name":"RMD Open","volume":"12 3","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13504899/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148797671","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring possibilities towards PeRsonalIsed MEdicine in Rheumatoid Arthritis (PRIMERA): tailored modifications to standard treat-to-target management-a multicentre, randomised, open-label trial.","authors":"Agnes E M Looijen, Hamit Harun Dag, Judith W Heutz, Floris A van Gaalen, Mirjam C Hegeman, Jos H van der Kaap, Lindy-Anne Korswagen, Roos C Padmos, Naghmeh Riyazi, Julia Spierings, Ilja Tchetverikov, Josien J Veris-van Dieren, Harald E Vonkeman, Annemiek Willemze, Annette H M van der Helm-van Mil, Pascal H P de Jong","doi":"10.1136/rmdopen-2026-007217","DOIUrl":"10.1136/rmdopen-2026-007217","url":null,"abstract":"<p><strong>Objectives: </strong>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).</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p><p><strong>Trial registration number: </strong>ISRCTN16170070.</p>","PeriodicalId":21396,"journal":{"name":"RMD Open","volume":"12 3","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13504905/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148797722","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prevalence and clinical relevance of anti-drug antibodies in psoriatic arthritis: a systematic review.","authors":"James Kimpton, Akpabio Akpabio, Andrew Watts, Sarah Tansley, Theresa Smith, Neil McHugh, William Tillett","doi":"10.1136/rmdopen-2026-007140","DOIUrl":"10.1136/rmdopen-2026-007140","url":null,"abstract":"<p><strong>Objectives: </strong>To determine the prevalence of anti-drug antibodies (ADAs) in patients with psoriatic arthritis (PsA) treated with biological disease-modifying antirheumatic drugs (bDMARDs) and to evaluate associations with serum drug levels, clinical efficacy and safety.</p><p><strong>Methods: </strong>A Preferred Reporting Items for Systematic Reviews and Meta-Analyses-guided systematic review was conducted. MEDLINE, Embase and Cochrane CENTRAL were searched from inception to September 2025. Randomised controlled trials and observational studies reporting ADA measurement in adults with PsA receiving bDMARDs were included. The risk of bias was assessed using the Cochrane Risk of Bias Tool 2 and the Risk of Bias in Non-randomised Studies of Interventions.</p><p><strong>Results: </strong>28 studies (19 randomised controlled trials and 9 observational studies) were included. ADA prevalence varied widely between bDMARDs and across studies of the same drug and was not directly comparable due to immunoassay heterogeneity. The highest ADA prevalence was observed with adalimumab, infliximab and golimumab followed by ustekinumab, ixekizumab, certolizumab pegol and guselkumab, while secukinumab and etanercept demonstrated very low or absent immunogenicity. Across tumour necrosis factor (TNF) inhibitor studies, ADAs were consistently associated with lower serum drug levels and reduced clinical response, while concomitant methotrexate was associated with lower ADA prevalence. In contrast, serum drug level and clinical outcome data for interleukin (IL)-17, IL-12/23 and IL-23 inhibitors were limited or lacking. Immunogenicity-related adverse events were uncommon, and evidence was insufficient to establish an association with ADAs across bDMARDs.</p><p><strong>Conclusion: </strong>ADA prevalence in PsA varies widely between bDMARDs and across studies of the same bDMARD. ADAs appear most clinically relevant for TNF inhibitors, whereas evidence for other biological classes remains limited. Immunoassay heterogeneity limits comparability, highlighting the need for standardised prospective studies.</p><p><strong>Prospero registration number: </strong>CRD420251121662.</p>","PeriodicalId":21396,"journal":{"name":"RMD Open","volume":"12 3","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13504906/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148797676","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integration of synovial pathotypes and serum proteomic modules as determinants of disease progression and therapeutic response in early rheumatoid arthritis.","authors":"Sagrario Corrales, Julio Osuna-Soto, Andrea Cid-Chaves, Rafaela Ortega-Castro, Lourdes Ladehesa-Pineda, Christian Merlo-Ruiz, Desirée Ruiz-Vílchez, Nuria Barbarroja, Fernando Leiva-Cepas, Carlos Perez-Sanchez, Marta Alarcón-Riquelme, Concepción Aranda-Valera, Alejandro Escudero-Contreras, Chary López-Pedrera","doi":"10.1136/rmdopen-2026-007196","DOIUrl":"10.1136/rmdopen-2026-007196","url":null,"abstract":"<p><strong>Background: </strong>Rheumatoid arthritis (RA) is characterised by marked clinical, histological and molecular heterogeneity, complicating treatment-response prediction. This study evaluated associations between synovial pathotypes, pathotype-associated serum proteomic patterns and 6-month clinical outcomes in early RA.</p><p><strong>Methods: </strong>A total of 147 patients with early RA were included in two independent cohorts. In cohort 1, 25 patients underwent synovial biopsy for histological classification by synovial pathotype and Krenn synovitis score. Serum samples collected at biopsy were analysed using the Olink Inflammation panel. Cohort 2, comprising 122 patients, was used to assess the directional consistency of associations between predefined serum proteomic scores and 6-month European Alliance of Associations for Rheumatology (EULAR) response.</p><p><strong>Results: </strong>The lymphomyeloid pathotype was associated with higher disease activity, autoantibody positivity and increased synovial immune infiltration. High Krenn score was also associated with greater inflammatory burden and higher disease activity. However, no significant differences in treatment response were observed according to Krenn score, whereas synovial pathotype was associated with differences in biological or targeted synthetic disease-modifying antirheumatic drug (b/tsDMARD) initiation and exploratory 6-month response patterns. Pathotype-associated serum protein patterns identified in cohort 1 showed differential distributions across histological groups. Higher lymphomyeloid scores were observed among conventional synthetic disease-modifying antirheumatic drug responders, whereas higher diffuse-myeloid scores were observed among b/tsDMARD non-responders. These treatment-stratified associations were exploratory and directionally consistent after adjustment in cohort 2, although neither reached statistical significance.</p><p><strong>Conclusion: </strong>Synovial pathotypes in early RA were associated with distinct circulating proteomic patterns reflecting tissue-level heterogeneity. This tissue-to-blood approach supports development of pathotype-associated serum profiles as candidate minimally invasive biomarkers and provides a promising framework for precision medicine in RA.</p>","PeriodicalId":21396,"journal":{"name":"RMD Open","volume":"12 3","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13504898/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148797673","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}