RMD Open最新文献

{"title":"To optimise the diagnostic process of rheumatic diseases affecting the hands using fluorescence optical imaging (FOI).","authors":"Nele Stumper, Jörn Berger, Jens Klotsche, Egbert Gedat, Paula Hoff, Gabriela Schmittat, Gerd R Burmester, Gerhard Krönke, Marina Backhaus, Ida K Haugen, Sarah Ohrndorf","doi":"10.1136/rmdopen-2024-005372","DOIUrl":"10.1136/rmdopen-2024-005372","url":null,"abstract":"<p><strong>Background: </strong>Accurate and rapid diagnosis of rheumatic diseases is essential for further treatment decision. Different rheumatic diseases present characteristic patterns (image features) in fluorescence optical imaging (FOI). We developed an atlas of FOI image features and tested its ability to differentiate various rheumatic diseases.</p><p><strong>Methods: </strong>FOI images from patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), connective tissue diseases (CTD) and osteoarthritis (OA) were analysed by two readers blinded for diagnosis and calibrated against each other, using the prima vista mode (PVM) and an automated 5-phase model. Twenty-six different reoccurring typical signal enhancement patterns (features) indicating inflamed joints, nail or skin were defined and all FOI images were scored accordingly. The feature frequency in each patient cohort and phase (PVM, 5-phase) was counted. Contingency tables were created with categorical variable counts and diagnosis using common formulae.</p><p><strong>Findings: </strong>Four hundred thirty-eight patients with RA (n=117), PsA (n=110), CTD (n=121) and OA (n=90) were included. Once the data had been categorised, a two-step diagnostic pathway was developed: in the first step, OA was best distinguished from the other diseases with high specificity by five patterns (specificity >0.9, diagnostic OR between 2.34 and 8.24). In a second step, the remaining autoimmune diseases were differentiated from each other by a certain number of features (five for RA, 12 for PsA and four for CTD).</p><p><strong>Interpretation: </strong>This was the first study to show that feature analysis in FOI helps to differentiate typical rheumatic diseases from each other, potentially simplifying and speeding up the diagnostic process. Therefore, FOI could be considered an additional component of a wider range of imaging techniques used in rheumatology.</p>","PeriodicalId":21396,"journal":{"name":"RMD Open","volume":"11 3","pages":""},"PeriodicalIF":4.7,"publicationDate":"2025-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12406893/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144966865","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":"Hydroxychloroquine and pregnancy outcomes in patients with anti-phospholipid syndrome: a systematic review and meta-analysis.","authors":"Aya Berman, Gili Kenet, Aharon Lubetsky, Nancy Agmon-Levin, Shelly Soffer, Assaf A Barg, Sarina Levy-Mendelovich, Omri Cohen, Liat Waldman-Radinsky, Shadan Lalezari, Eyal Klang, Orly Efros","doi":"10.1136/rmdopen-2025-005825","DOIUrl":"10.1136/rmdopen-2025-005825","url":null,"abstract":"<p><strong>Background: </strong>About 20% of female patients with anti-phospholipid syndrome (APS) experience obstetric complications despite standard treatment with aspirin and heparin. Treatment with hydroxychloroquine (HCQ) was shown to reduce disease flares during pregnancy in patients with systemic lupus erythematosus and to improve pregnancy outcomes.</p><p><strong>Objectives: </strong>To evaluate the impact of HCQ on live birth and obstetric complication rates in pregnant women diagnosed with APS.</p><p><strong>Methods: </strong>We systematically searched PubMed and EMBASE databases in April 2024 for original, peer-reviewed studies on HCQ efficacy and safety in APS patients. The main outcomes measured were live births and obstetric complications, comparing HCQ plus standard therapy to standard therapy alone.</p><p><strong>Results: </strong>Seven observational studies met our inclusion criteria, comprising a total of 750 patients included in the meta-analysis. The overall pooled proportions of live births in the HCQ group were 89.9% (95% CI 76.5% to 96.0%; <i>I</i> ²=81%) and 73.9% (95% CI 51.8% to 88.2%; <i>I</i> ²=81%) in the non-HCQ-treated group. The overall pooled proportion of obstetric complications occurred in 19.3% (95% CI 9.4% to 35.4; <i>I</i> ²=81%; four studies) of the HCQ group and 55.0% (95% CI 39.4 to 69.7; <i>I</i> ²=79%; four studies) of the non-HCQ treated group. Treatment with HCQ was associated with higher rates of live births (OR 2.66; 95% CI 1.44 to 4.91) and lower obstetric complications (OR 0.19; 95% CI 0.19 to 0.39) compared with non-HCQ treatment. HCQ treatment during pregnancy was well tolerated.</p><p><strong>Conclusions: </strong>Our findings suggest that HCQ may offer potential benefits to APS patients during pregnancy by increasing the probability of live birth rates and lowering the risk for obstetric complications.</p><p><strong>Prospero registration number: </strong>The study was registered with PROSPERO, the prospective international register of systematic reviews (identification number CRD42024574097).</p>","PeriodicalId":21396,"journal":{"name":"RMD Open","volume":"11 3","pages":""},"PeriodicalIF":4.7,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12410631/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144966589","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 of risankizumab across GRAPPA domains in psoriatic arthritis: a pooled analysis of patients from the phase 3 KEEPsAKE 1 and 2 studies.","authors":"Laura C Coates, Ricardo Blanco, Frank Behrens, Alexis Ogdie, Filip Van den Bosch, Roberto Ranza, Yael Klionsky, Ahmed M Soliman, Michael Chen, Derek Coombs, Linyu Shi, Jamie R Urbanik, Thomas Iyile, Ralph Lippe, Laure Gossec","doi":"10.1136/rmdopen-2025-005522","DOIUrl":"10.1136/rmdopen-2025-005522","url":null,"abstract":"<p><strong>Objective: </strong>To assess the efficacy of long-term treatment with risankizumab across the updated Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) domains and key related conditions of psoriatic arthritis (PsA).</p><p><strong>Methods: </strong>This post hoc analysis primarily used data from the phase 3 KEEPsAKE 1 trial of adult patients with PsA, with data from KEEPsAKE 2 pooled for prespecified outcomes. Outcomes measuring risankizumab efficacy across key GRAPPA-recognised domains of PsA (peripheral arthritis, enthesitis, dactylitis, skin and nail psoriasis, axial disease) and PsA-related conditions such as inflammatory bowel disease (IBD) and uveitis were assessed over 100 weeks of treatment (~2 years). Statistical approaches included non-responder imputation (as-observed with imputation) for categorical variables and mixed-effect model for repeated measures for continuous variables including as-observed measurements at all visits. PsA-related conditions were evaluated via adverse events through 100 weeks.</p><p><strong>Results: </strong>Overall, in KEEPsAKE 1 and KEEPsAKE 2, 412/483 (85.3%) and 181/224 (80.8%) of patients randomised to risankizumab completed treatment to week 100. Risankizumab demonstrated efficacy across all GRAPPA-defined domains through 100 weeks, including swollen and tender joint counts, enthesitis, dactylitis, skin and nail outcomes, and axial disease. In KEEPsAKE 1, 42.4% of patients had achieved a Disease Activity in Psoriatic Arthritis measurement of low disease activity and 62.9% had reached a minimal clinically important difference in pain at week 100. Rates of new onset or flare of IBD and uveitis were low.</p><p><strong>Conclusions: </strong>Treatment with risankizumab provides durable improvement in the signs and symptoms of PsA across all GRAPPA disease domains and related conditions.</p>","PeriodicalId":21396,"journal":{"name":"RMD Open","volume":"11 3","pages":""},"PeriodicalIF":4.7,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12382576/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144967124","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":"Shared genetic susceptibility between idiopathic inflammatory myopathies and common B cell lymphoma subtypes found primarily in the human leucocyte antigen region.","authors":"Weng Ian Che, Anton Öberg Sysojev, Catherine Zhu, Karina Patasova, Karin E Smedby, Ingrid E Lundberg, Helga Westerlind, Marie Holmqvist","doi":"10.1136/rmdopen-2025-006035","DOIUrl":"https://doi.org/10.1136/rmdopen-2025-006035","url":null,"abstract":"<p><strong>Objectives: </strong>To estimate shared genetic susceptibility between major subtypes of idiopathic inflammatory myopathies (IIM) and B cell lymphomas.</p><p><strong>Methods: </strong>We paired summary statistics from genome-wide association studies (GWASs) of diffuse large B cell lymphoma, follicular lymphoma (FL), chronic lymphocytic leukaemia (CLL) and marginal zone lymphoma with those of dermatomyositis (DM) and polymyositis (PM) from a GWAS and an ImmunoChip study. We estimated local genetic correlation (r_g) for each disease pair using local analysis of (co)variant association (Bonferroni-corrected p value<0.05) and identified genetic variants jointly associated with both diseases using pleiotropy-informed false discovery rate (conjunctional false discovery rate <0.05). Functional mapping and annotation analyses were also performed.</p><p><strong>Results: </strong>We identified significant r_g (ranging from -0.50 to 0.84) across 16 loci, with half located in the human leucocyte antigen (HLA) region, for the disease pairs of IIM and B cell lymphoma subtypes. Furthermore, jointly associated single-nucleotide polymorphisms were predominantly found in the HLA region. Specifically, all disease pairs showed shared genetic susceptibility in the HLA class I regions, while additional correlations in class III and class II regions were specific to DM and PM disease pairs, respectively. For some non-HLA loci with significant r_g, functional analyses revealed immune-related responses potentially overlapping between DM and FL, DM and CLL, and PM and CLL.</p><p><strong>Conclusion: </strong>We revealed that DM and PM share genetic susceptibility with common B cell lymphoma subtypes in both immune-related loci and loci with unclear biological functions. These novel findings improve our understanding of the pathological link between IIM and B cell lymphomas.</p>","PeriodicalId":21396,"journal":{"name":"RMD Open","volume":"11 3","pages":""},"PeriodicalIF":4.7,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12382563/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144966643","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":"2023 ACR/EULAR classification criteria for antiphospholipid syndrome: more lights rise but shade remains.","authors":"Jaume Alijotas-Reig, Francesc Miro-Mur, Ariela Hoxha, Munther A Khamashta, Yehuda Shoenfeld","doi":"10.1136/rmdopen-2025-006014","DOIUrl":"10.1136/rmdopen-2025-006014","url":null,"abstract":"<p><p>Antiphospholipid syndrome (APS) is an autoimmune disorder for which there are no universally accepted diagnostic criteria, although classification criteria do exist, as is the case with most autoimmune diseases. Until 2023, the 2006 Sydney classification criteria were in use. Although originally intended for research purposes, these criteria have often been employed in clinical practice as a substitute for diagnostic guidelines, thereby conflating classification with diagnosis. In July 2023, ACR and European Alliance of Associations for Rheumatology convened a panel of experts to revise these criteria. The newly published classification criteria are explicitly intended for research use only. They place a strong emphasis on specificity-99%-but this comes at the expense of sensitivity-84%. The updated criteria encompass six clinical domains and two laboratory domains. Notably, the inclusion of new clinical features, such as thrombocytopenia, cardiac valve involvement and microvascular thrombosis, has broadened patient inclusion and, indirectly, aided the diagnostic process. However, a significant proportion of patients with suspected antiphospholipid antibody-related conditions may no longer meet the criteria for APS classification. In real-world settings, this could result in these individuals being denied appropriate management, thereby increasing their risk of subsequent thrombotic or obstetric events, as has already been demonstrated.This manuscript examines the advantages and limitations of the new clinical and laboratory domains, considering their implications not only from a research but also from a clinical perspective, APS.</p>","PeriodicalId":21396,"journal":{"name":"RMD Open","volume":"11 3","pages":""},"PeriodicalIF":4.7,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12382538/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144967073","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 as monotherapy or combined with elsubrutinib for the treatment of systemic lupus erythematosus: results through 104 weeks in a long-term extension study.","authors":"Joan T Merrill, Amit Saxena, Martin Aringer, Yoshiya Tanaka, Xiaofeng Zeng, Ling Cheng, Thao T Doan, David D'Cruz, Karim R Masri, Kristin M D'Silva","doi":"10.1136/rmdopen-2025-005742","DOIUrl":"10.1136/rmdopen-2025-005742","url":null,"abstract":"<p><strong>Objectives: </strong>This 1-year long-term extension (LTE) study (NCT04451772) followed the 48-week phase 2 SLEek study (NCT03978520) that evaluated upadacitinib (a Janus kinase inhibitor) alone or combined with elsubrutinib (a Bruton's tyrosine kinase inhibitor) in adults with moderately to severely active systemic lupus erythematosus (SLE). The objective was to evaluate the efficacy and safety of an additional 56 weeks of treatment.</p><p><strong>Methods: </strong>Patients randomised to upadacitinib 30 mg one time per day (QD) or upadacitinib 30 mg/elsubrutinib 60 mg QD (upadacitinib/elsubrutinib) in the SLEek study continued their assigned treatment during the LTE. Patients originally receiving placebo switched to upadacitinib/elsubrutinib in the LTE. Assessments through week 104 included SLE Responder Index-4 (SRI-4), British Isles Lupus Assessment Group-based Combined Lupus Assessment (BICLA), Lupus Low Disease Activity State (LLDAS), change from baseline in glucocorticoid dose, flare events and adverse events.</p><p><strong>Results: </strong>This LTE analysis included 127 patients. Efficacy responses for the groups receiving upadacitinib, upadacitinib/elsubrutinib and placebo to upadacitinib/elsubrutinib were maintained or increased from weeks 48 to 104 (week 104: SRI-4: 82.1%, 85.4% and 61.3%; BICLA: 69.2%, 78.0% and 54.8%; LLDAS: 60.0%, 78.0% and 34.4%). From weeks 48 through 104, the mean daily glucocorticoid dose was reduced, and the incidence of flares was maintained or further reduced in all treatment groups. Safety profiles were similar to those observed in the primary SLEek study.</p><p><strong>Conclusions: </strong>In this LTE study, upadacitinib monotherapy and upadacitinib/elsubrutinib combined were well tolerated and continued to demonstrate beneficial effects on SLE disease activity, glucocorticoid dose and flares through 104 weeks.</p>","PeriodicalId":21396,"journal":{"name":"RMD Open","volume":"11 3","pages":""},"PeriodicalIF":4.7,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12366599/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144883555","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":"Histological synovitis and radiographic damage in knee osteoarthritis: insights from a comprehensive analysis of ultrasound-guided synovial biopsies in 161 patients.","authors":"Pietro Rubortone, Enrico De Lorenzis, Flavia Leone, Barbara Tolusso, Dario Bruno, Marco Gessi, Maria-Antonietta D'Agostino, Stefano Alivernini, Marco Maria Lizzio","doi":"10.1136/rmdopen-2025-006011","DOIUrl":"10.1136/rmdopen-2025-006011","url":null,"abstract":"<p><strong>Objective: </strong>Synovial inflammation plays a crucial role in osteoarthritis (OA) by producing key cytokines that mediate synovium-cartilage interaction and drive damage progression. In this study, we aimed to evaluate relationships between histological features of synovitis, radiographic damage and patients' clinical characteristics.</p><p><strong>Methods: </strong>This observational cross-sectional study included consecutive patients with knee OA from 2016 to 2022. Enrolled patients were aged between 40 and 90 years, had chronic knee pain lasting at least 3 months and showed ultrasound evidence of synovitis. All patients underwent a general rheumatological evaluation, including the collection of clinical and laboratory data and ultrasound (US)-guided minimally invasive synovial tissue biopsy. The severity of synovitis was assessed by histology using the Krenn Synovitis Score (KSS).</p><p><strong>Results: </strong>A total of 161 patients were considered for the analysis. The multivariate analysis showed that both US effusion and Kellgren-Lawrence (KL) grade were positively associated with histological synovitis. In contrast, age, sex, body mass index, levels of inflammatory markers, pain intensity and cardiovascular risk factors were not associated with histological synovitis. A strong positive correlation was found between KL grades and the KSS. A moderate positive correlation emerged between KL grades and the proportion of patients with lymphocytes and plasma cells in synovial tissue.</p><p><strong>Conclusions: </strong>More severe histological synovitis in patients with non-end-stage knee OA is associated with worse radiographic structural damage. In the advanced stages of structural damage, the likelihood of detecting a lymphoplasmacytic inflammatory infiltrate in the synovial membrane increases. US-detected effusion serves as a marker of histological synovitis.</p>","PeriodicalId":21396,"journal":{"name":"RMD Open","volume":"11 3","pages":""},"PeriodicalIF":4.7,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12366559/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144883556","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":"Using ultrasound to define inflammatory and non-inflammatory phenotypes in difficult-to-treat psoriatic arthritis.","authors":"Alen Zabotti, Nicola Cabas, Cristina Di Nicola, Fabio Massimo Perrotta, Andrea Guiotto, Nicoletta Franzolini, Ivan Giovannini, Maria De Martino, Miriam Isola, Andrea Di Matteo, Gabriele De Marco, Dennis McGonagle, Ennio Lubrano, Luca Quartuccio","doi":"10.1136/rmdopen-2025-005785","DOIUrl":"10.1136/rmdopen-2025-005785","url":null,"abstract":"<p><strong>Objective: </strong>To investigate the prevalence of difficult-to-treat psoriatic arthritis (D2T-PsA) and classify patients with persistent inflammatory PsA (PIPsA) and non-inflammatory PsA (NIPsA) based on a combination of clinical and musculoskeletal ultrasound (MSUS) evidence of inflammation.</p><p><strong>Methods: </strong>A multicentre cross-sectional study was conducted on PsA patients treated with biological disease-modifying anti-rheumatic drugs/targeted synthetic disease-modifying anti-rheumatic drugs (b/tsDMARDs). D2T-PsA status was characterised by an inadequate response to ≥2 classes of b/tsDMARDs and the persistence of active disease, defined as a DAPSA >14.</p><p><strong>Results: </strong>Out of 517 PsA patients on b/tsDMARDs, 53 (10.3%) met the criteria for D2T-PsA with 30 (57%) classified as PIPsA and 23 (43%) classified as NIPsA. The PIPsA phenotype had higher swollen joint count (2.5 (IQR 1.0-7.0) vs 0.0 (IQR 0.0-1.0), p<0.001), dactylitis (20% vs 0%, p=0.030) and nail psoriasis (40% vs 13%, p=0.027). Conversely, NIPsA patients had significantly greater ΔPtGA-PhGA (4.0 (IQR 2.5-5.0) vs 0.0 (IQR 0.0-1.5), p<0.001), higher tender points (16.0 (IQR 0.0-18.0) vs 0.0 (IQR 0.0-8.0), p=0.009), a higher SPARCC enthesitis index (5.0 (IQR 2.0-8.0) vs 2.0 (IQR 0.0-5.0), p=0.023). The MSUS showed higher ultrasound activity (3.81±2.0 vs 0.91±0.5, p<0.001) and greater structural damage (4.12±1.0 vs 2.38±2.1, p<0.001), with both activity and damage scores being higher in PIPsA patients.</p><p><strong>Conclusion: </strong>The classification into PIPsA and NIPsA based on easily detectable clinical features can support a tailored therapeutic management of patients with D2T-PsA.</p>","PeriodicalId":21396,"journal":{"name":"RMD Open","volume":"11 3","pages":""},"PeriodicalIF":4.7,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12352194/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144856186","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, pharmacokinetics and safety of iscalimab (CFZ533) in patients with proliferative lupus nephritis: a randomised, double-blind, placebo-controlled, phase II study.","authors":"Nan Shen, Julia Weinmann-Menke, Ana Malvar, André Serra-Roma, Markus Weiss, Rambabu Danekula, Carole Sips, Jan Rohr, Renaud Felten, Peter Gergely, Tamas Shisha","doi":"10.1136/rmdopen-2025-005557","DOIUrl":"10.1136/rmdopen-2025-005557","url":null,"abstract":"<p><strong>Background: </strong>Iscalimab (CFZ533) is a novel, anti-CD40 monoclonal antibody. This study evaluated the efficacy, pharmacokinetics and safety of iscalimab versus placebo as add-on to standard-of-care (SoC) therapy in patients with biopsy-proven active proliferative lupus nephritis (LN).</p><p><strong>Methods: </strong>This was a phase II, randomised, double-blind, placebo-controlled, multicentre study including patients with a diagnosis of systemic lupus erythematosus with active LN. Patients were randomly assigned (2:1) to receive either intravenous iscalimab (10 mg/kg) or placebo for 24 weeks on top of SoC for LN. The primary efficacy endpoint was the ratio from baseline in urinary protein-to-creatinine ratio (UPCR) at week 24. Safety assessments included adverse events (AEs) and serious AEs (SAEs) during treatment and follow-up up to 49 weeks.</p><p><strong>Findings: </strong>Of the 57 patients (iscalimab, n=39; placebo, n=18) randomised, 31 (54.4%) completed the study. The primary efficacy endpoint was met: at week 24, the relative improvement from baseline in proteinuria (UPCR) was 63.1% and 36.3% in the iscalimab and placebo arms, respectively. UPCR to baseline at week 24 showed a statistically significant reduction of 42.1% in the iscalimab versus placebo arm. Most AEs were of mild to moderate severity in both treatment arms. Overall, seven SAEs were reported in six patients (15.4%) in the iscalimab arm versus four in three patients (16.7%) in the placebo arm.</p><p><strong>Interpretation: </strong>Iscalimab showed a significant improvement in proteinuria (UPCR) in patients with active LN. Iscalimab was generally well tolerated with the exception of a few severe infections and one case of macrophage-activation syndrome in immunosuppressed and comorbid patients.</p><p><strong>Trial registration number: </strong>NCT03610516.</p>","PeriodicalId":21396,"journal":{"name":"RMD Open","volume":"11 3","pages":""},"PeriodicalIF":4.7,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12352177/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144856185","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":"Correction: Effectiveness of ixekizumab in 709 real-world patients with axial spondyloarthritis and psoriatic arthritis: a nationwide cohort study.","authors":"","doi":"10.1136/rmdopen-2025-005806corr1","DOIUrl":"10.1136/rmdopen-2025-005806corr1","url":null,"abstract":"","PeriodicalId":21396,"journal":{"name":"RMD Open","volume":"11 3","pages":""},"PeriodicalIF":4.7,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12352248/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144848591","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}