Lancet Rheumatology最新文献

{"title":"Serum biomarkers associated with baricitinib response in patients with juvenile idiopathic arthritis: a post-hoc analysis of the phase 3 JUVE-BASIS trial.","authors":"Venkatesh Krishnan, Stuart Y Keller, Christine Chew, Jonathan T Sims, Ching-Yun Chang, Ernst R Dow, Robert J Benschop, Rona Wang, Athimalaipet V Ramanan","doi":"10.1016/S2665-9913(25)00153-5","DOIUrl":"https://doi.org/10.1016/S2665-9913(25)00153-5","url":null,"abstract":"<p><strong>Background: </strong>Baricitinib has previously been shown to improve clinical response in patients with juvenile idiopathic arthritis (JIA) in the JUVE-BASIS trial. In this post-hoc analysis we aimed to identify whether pharmacodynamic changes in serum biomarkers in response to baricitinib treatment could help reaffirm the clinical utility of baricitinib in patients with JIA.</p><p><strong>Methods: </strong>JUVE-BASIS was a randomised, double-blind, placebo-controlled, withdrawal, efficacy, safety, phase 3 trial, done in 75 centres in 20 countries. Eligible patients were children and adolescents (aged 2 to <18 years), with polyarticular JIA (positive or negative for rheumatoid factor), extended oligoarticular JIA, enthesitis-related arthritis, or juvenile psoriatic arthritis, as per the International League of Associations for Rheumatology criteria and an inadequate response (≥12 weeks) or intolerance to one or more conventional synthetic or biological disease-modifying antirheumatic drugs (DMARDs). Here we report post-hoc analyses of serum samples from patients who received open-label baricitinib in the 12-week lead-in period of the JUVE-BASIS trial. Samples were assessed using an Olink Explore 3072 panel at baseline and week 12. Baricitinib-mediated pharmacodynamic changes in serum protein markers were measured as changes from baseline to week 12 derived from a mixed model with repeated measurement. Pearson correlations of the change in serum biomarkers and clinical disease activity (JADAS-27 scores) comparing baseline with week 12 were examined. Proportional changes in biomarkers were classified into three response subsets based on JIA-ACR response rates: JIA-ACR <30% (non-responders), JIA-ACR 30-70% (responders), and JIA-ACR 70-100% (super-responders). People with lived experience of JIA were not involved in the design or conduct of this study. The JUVE-BASIS trial was registered with ClinicalTrials.gov, NCT03773978, and is completed.</p><p><strong>Findings: </strong>Between Dec 17, 2018 and March 3, 2021, 220 patients were enrolled in JUVE-BASIS and received at least one dose of baricitinib in the open-label lead-in period. In this post-hoc analysis, 168 serum samples from 84 patients were analysed: 67 (80%) of 84 patients were female, 17 (20%) were male, 67 (80%) were White and the mean age was 14 years (SD 2). 10 (12%) of 84 were non-responders, 27 (32%) were responders, and 47 (56%) were super-responders based on clinical response. Several serum biomarkers showed significant changes following 12 weeks of baricitinib treatment for all patients with higher magnitude changes seen in responders and super-responders. Changes in biomarkers associated with macrophage activation (CCL7, CCL18, and IL-6) and regulation of matrix composition (matrix metalloproteinase-3) were positively correlated with clinical response.</p><p><strong>Interpretation: </strong>To our knowledge, this is the first study measuring serum protein markers in the","PeriodicalId":48540,"journal":{"name":"Lancet Rheumatology","volume":" ","pages":""},"PeriodicalIF":16.4,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145015289","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"VEXAS syndrome and immune-mediated rheumatic diseases: overlaps in clinical features and mechanisms","authors":"Arvind Kaul PhD ,&nbsp;Adam Al-Hakim MRCP ,&nbsp;Prof Helen Lachmann FMedSci ,&nbsp;Austin Kulasekararaj MD ,&nbsp;Prof Sinisa Savic PhD","doi":"10.1016/S2665-9913(25)00197-3","DOIUrl":"10.1016/S2665-9913(25)00197-3","url":null,"abstract":"<div><div>Vacuoles, E1 enzyme, X-linked, autoinflammatory, and somatic (VEXAS) syndrome is a newly identified disorder caused by an acquired monogenic somatic <em>UBA1</em> gene mutation, affecting nuclear and cytoplasmic ubiquitination. This mutation triggers immune dysregulation, leading to diverse clinical and pathological features resembling inflammatory rheumatic diseases. Blood abnormalities stem from myeloid precursor dysfunction, presenting as elevated concentrations of inflammatory markers and cytokines, leukopenia, and macrocytosis. These abnormalities can lead to inflammatory arthritis, vasculitis, polychondritis, thrombosis, and connective tissue disease-like syndromes. This Review explores the clinical and mechanistic links between VEXAS syndrome and rheumatic diseases, offering guidance on current best management strategies. Although rare, VEXAS syndrome has high morbidity and mortality, providing valuable insights into how genetic mutations drive immune system activation and rheumatic disease development.</div></div>","PeriodicalId":48540,"journal":{"name":"Lancet Rheumatology","volume":"7 10","pages":"Pages e719-e733"},"PeriodicalIF":16.4,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145015267","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mapping the infectious burden in VEXAS syndrome: a systematic review and rationale for prevention","authors":"Valentine Ribier MD ,&nbsp;Jérôme Hadjadj MD ,&nbsp;Vincent Jachiet MD ,&nbsp;Prof Arsène Mekinian MD ,&nbsp;Prof Benjamin Terrier MD ,&nbsp;Prof Sophie Georgin-Lavialle MD ,&nbsp;Peter C Grayson MD ,&nbsp;David B Beck PhD ,&nbsp;Prof Sinisa Savic MD ,&nbsp;Prof Vincent Dubée MD ,&nbsp;Valentin Lacombe MD","doi":"10.1016/S2665-9913(25)00225-5","DOIUrl":"10.1016/S2665-9913(25)00225-5","url":null,"abstract":"<div><div>Infections are increasingly recognised as a major cause of morbidity and mortality in patients with vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome. We conducted a systematic review to characterise the infectious burden of VEXAS syndrome and propose preventive strategies. We included 57 studies (813 patients) showing that infections in patients with VEXAS syndrome were frequent, severe in 40–60% of cases, and fatal in 6–15% of cases. Pulmonary infections were most common, followed by cutaneous infections and bacteraemia. Opportunistic pathogens, such as <em>Pneumocystis jirovecii</em>, <strong>Legionella pneumophila</strong>, non-tuberculous mycobacteria, and varicella zoster virus, were frequently reported, even in patients not receiving immunosuppressive therapy, which suggests intrinsic immune dysfunction. Prophylaxis with co-trimoxazole (or other <em>Pneumocystis</em> prophylaxis, such as atovaquone or pentamidine) and valaciclovir should particularly be considered for patients at high risk of infection, including those receiving immunosuppressive therapy and those with lymphopenia, pMet41Val mutation, or previous severe or recurrent infections. Posaconazole might be appropriate in patients with neutropenia who are taking azacitidine. Vaccination against <em>Streptococcus pneumoniae</em>, varicella zoster virus, influenza, and SARS-CoV-2 is recommended. These data highlight the need to integrate infectious risk into VEXAS syndrome management and to evaluate preventive strategies in prospective studies.</div></div>","PeriodicalId":48540,"journal":{"name":"Lancet Rheumatology","volume":"7 10","pages":"Pages e734-e744"},"PeriodicalIF":16.4,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145015235","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biomarkers for juvenile idiopathic arthritis treatment response-have we identified them?","authors":"Stephanie Ka Wong, Marinka Twilt","doi":"10.1016/S2665-9913(25)00189-4","DOIUrl":"https://doi.org/10.1016/S2665-9913(25)00189-4","url":null,"abstract":"","PeriodicalId":48540,"journal":{"name":"Lancet Rheumatology","volume":" ","pages":""},"PeriodicalIF":16.4,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145015246","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Challenges in the therapeutic management of psoriatic arthritis.","authors":"Dafna D Gladman","doi":"10.1016/S2665-9913(25)00255-3","DOIUrl":"https://doi.org/10.1016/S2665-9913(25)00255-3","url":null,"abstract":"","PeriodicalId":48540,"journal":{"name":"Lancet Rheumatology","volume":" ","pages":""},"PeriodicalIF":16.4,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145008590","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of a treatment strategy utilising golimumab, methotrexate and corticosteroids versus methotrexate and corticosteroids in early, untreated psoriatic arthritis (GOLMePsA): a single-centre, double-blind, parallel-group, randomised controlled trial.","authors":"Gabriele De Marco, Elizabeth M A Hensor, Philip S Helliwell, Shabina Sultan, Sayam R Dubash, Xabier Michelena, Laura C Coates, Paul Emery, Ai Lyn Tan, Dennis McGonagle, Helena Marzo-Ortega","doi":"10.1016/S2665-9913(25)00156-0","DOIUrl":"https://doi.org/10.1016/S2665-9913(25)00156-0","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;The optimal treatment strategy in early psoriatic arthritis remains unknown. We aimed to assess whether the combination of methotrexate and golimumab plus corticosteroids is superior to methotrexate plus corticosteroids in reducing disease activity in early, untreated psoriatic arthritis.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We did a double-blind, randomised, placebo-controlled, parallel-group, single-centre study in adults with treatment-naïve active psoriatic arthritis. Participants were required to have been diagnosed up to 24 months before enrolment and had to be naïve to conventional synthetic, biologic, or targeted synthetic disease-modifying antirheumatic drugs or systemic treatments before enrolment. Participants were randomly assigned (1:1) to receive either combination therapy of golimumab and methotrexate or placebo and methotrexate, stratified by the number of involved peripheral joints at baseline. Investigators and participants were masked to treatment allocation. At baseline, all participants received methylprednisolone (120 mg intramuscular administration, single dose) and commenced weekly methotrexate (increased to 25 mg within 28 days). Golimumab or placebo were administered by subcutaneous injections every 4 weeks. By week 24, additional methylprednisolone was permitted once (totalling up to 240 mg exposure). The primary endpoint was the difference in mean Psoriatic Arthritis Disease Activity Score (PASDAS) at week 24 in the intention-to-treat population, compared using analysis of covariance via multiple linear regression. People with lived experience of psoriatic arthritis were involved in the design and conduct the study. The study was registered with EudraCT, 2013-004122-28, and is complete.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Findings: &lt;/strong&gt;Between Nov 3, 2015 and Jan 26, 2022, 106 people were assessed for eligibility, 22 were excluded, and 84 were randomly assigned (43 to the golimumab and methotrexate group and 41 to the placebo and methotrexate group). 46 (55%) participants were male and 38 (45%) were female. The mean age was 42·5 years (SD 12·4) and 61 (73%) participants were White and seven (8%) were from any Asian, Black, or other ethnic background. PASDAS did not differ between treatment groups at week 24 (unadjusted mean 3·09 [SD 1·32] in the placebo and methotrexate group and 2·70 [1·38] in the golimumab and methotrexate group; adjusted difference -0·55 [95% CI -1·12 to 0·03]; p=0·064). More participants in the placebo and methotrexate group received additional corticosteroids before week 24 (20 [49%] of 41 vs nine [21%] of 43; odds ratio 0·28 [95% CI 0·11 to 0·72]; p=0·009). Similar numbers of participants had adverse events (38 [93%] of 41 in the placebo and methotrexate group vs 41 [95%] of 43 in the golimumab and methotrexate group; risk difference 0·03 [95% CI -0·09 to 0·15]), although altered laboratory investigations and infections occurred more frequently in the golimumab and methotrexate group. N","PeriodicalId":48540,"journal":{"name":"Lancet Rheumatology","volume":" ","pages":""},"PeriodicalIF":16.4,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145008592","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From whole-brain metrics to circuit-specific precision: advancing fMRI biomarkers for TNF inhibitor response in rheumatoid arthritis.","authors":"Aikeremujiang Muheremu, Kan Jiang","doi":"10.1016/S2665-9913(25)00213-9","DOIUrl":"https://doi.org/10.1016/S2665-9913(25)00213-9","url":null,"abstract":"","PeriodicalId":48540,"journal":{"name":"Lancet Rheumatology","volume":" ","pages":""},"PeriodicalIF":16.4,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144974469","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From whole-brain metrics to circuitspecific precision: advancing fMRI biomarkers for TNF inhibitor response in rheumatoid arthritis - Authors' reply.","authors":"Andreas Hess, Koray Tascilar, Georg Schett, Jürgen Rech","doi":"10.1016/S2665-9913(25)00212-7","DOIUrl":"https://doi.org/10.1016/S2665-9913(25)00212-7","url":null,"abstract":"","PeriodicalId":48540,"journal":{"name":"Lancet Rheumatology","volume":" ","pages":""},"PeriodicalIF":16.4,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144974512","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ILD in rheumatic disease: navigating complexity","authors":"The Lancet Rheumatology","doi":"10.1016/S2665-9913(25)00228-0","DOIUrl":"10.1016/S2665-9913(25)00228-0","url":null,"abstract":"","PeriodicalId":48540,"journal":{"name":"Lancet Rheumatology","volume":"7 9","pages":"Page e591"},"PeriodicalIF":16.4,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144863307","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Narendra Kumar Bagri: taking paediatric rheumatology in India to new heights","authors":"Heather Van Epps","doi":"10.1016/S2665-9913(25)00227-9","DOIUrl":"10.1016/S2665-9913(25)00227-9","url":null,"abstract":"","PeriodicalId":48540,"journal":{"name":"Lancet Rheumatology","volume":"7 9","pages":"Page e606"},"PeriodicalIF":16.4,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144864192","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}