Rheumatology最新文献

{"title":"Mycophenolate mofetil directly modulates myeloid viability and pro-fibrotic activation of human macrophages.","authors":"Emily A Morris, Rezvan Parvizi, Nicole M Orzechowski, Michael L Whitfield, Patricia A Pioli","doi":"10.1093/rheumatology/keae517","DOIUrl":"10.1093/rheumatology/keae517","url":null,"abstract":"<p><strong>Objectives: </strong>Mycophenolate mofetil (MMF) is an immunosuppressant used to treat rheumatological diseases, including systemic sclerosis (SSc). While MMF is an established inhibitor of lymphocyte proliferation, recent evidence suggests MMF also mediates effects on other cell types. The goal of this study was to determine the effect of MMF on monocytes and macrophages, which have been implicated in SSc pathogenesis.</p><p><strong>Methods: </strong>Human monocyte-derived macrophages were cultured with the active MMF metabolite, mycophenolic acid (MPA), and assessed for changes in viability and immuno-phenotype. Guanosine supplementation studies were performed to determine whether MPA-mediated effects were dependent on de novo purine synthesis. The ability of MPA-treated macrophages to induce fibroblast activation was evaluated, and dermal myeloid expression signatures were analysed in MMF-treated SSc patients.</p><p><strong>Results: </strong>MPA reduced viability and induced apoptosis in monocytes and macrophages at doses (average IC50 = 1.15 µg/ml) within the target serum concentration of MMF-treated SSc patients (1-3 µg/ml). These effects were reversed by guanosine supplementation. Low-dose MPA (0.5 µg/ml) attenuated IL-4 or SSc plasma-mediated macrophage activation, and inhibited the ability of SSc plasma-activated macrophages to induce SSc fibroblast activation. Gene expression studies demonstrated significant reductions in dermal myeloid signatures in MMF-responsive SSc patients.</p><p><strong>Conclusion: </strong>For the first time, we have demonstrated that MMF inhibits the viability and pro-fibrotic activation of human monocytes and macrophages, which is dependent on de novo purine synthesis. Coupled with myeloid gene expression attenuation following MMF treatment in patients, these results suggest that the fibrotic inhibition observed with MMF may be attributable, at least in part, to direct effects on myeloid cells.</p>","PeriodicalId":21255,"journal":{"name":"Rheumatology","volume":" ","pages":"3125-3133"},"PeriodicalIF":4.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12048068/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142308550","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":"Drug-induced liver injury related to avacopan therapy.","authors":"Kentaro Mori, Tsuyoshi Shirai, Tomoyuki Mutoh, Jun Inoue, Fumiyoshi Fujishima, Satsuki Kubo, Hirofumi Watanabe, Satoko Sato, Mamoru Narita, Yosuke Hoshi, Hiroko Sato, Hiroshi Fujii","doi":"10.1093/rheumatology/keae689","DOIUrl":"10.1093/rheumatology/keae689","url":null,"abstract":"<p><strong>Objectives: </strong>The efficacy of avacopan as remission induction therapy for Anti-Neutrophil Cytoplasmic Autoantibody (ANCA)-associated vasculitis (AAV) is well-established. However, concerns regarding liver injury post-avacopan treatment remain, especially in Japan. Therefore, this study aimed to investigate drug-induced liver injury (DILI) associated with avacopan treatment.</p><p><strong>Methods: </strong>This study included 22 patients with AAV who were treated with avacopan at multiple centres in Japan between September 2021 and March 2024. DILI was assessed by the Japanese version of a revised electronic causality assessment method (RECAM-J 2023).</p><p><strong>Results: </strong>Among the 22 patients treated with avacopan, DILI was observed in nine cases (40.9%): six with microscopic polyangiitis and three with granulomatosis with polyangiitis. Severe DILI with elevated total bilirubin (T-Bil) was observed in four of the nine patients (44.4%), a few weeks after the initiation of avacopan therapy. Eight of the nine patients (88.9%) with DILI improved after discontinuation of avacopan and other medications, and one patient developed vanishing bile duct syndrome (VBDS) leading to death. Avacopan-induced DILI was classified into three patterns: 1, short-term injury without T-Bil elevation; 2, transient cholestatic liver injury with T-Bil elevation; 3, decompensated liver injury with marked T-Bil elevation (VBDS). The risk factors for severe DILI with T-Bil elevation in Japanese patients included older age, lower body mass index and early onset DILI following the initiation of avacopan treatment.</p><p><strong>Conclusion: </strong>Avacopan-induced DILI is relatively common in Japan and could be lethal. Frequent laboratory follow-ups should be considered, especially for elderly and low-body-weight patients.</p>","PeriodicalId":21255,"journal":{"name":"Rheumatology","volume":" ","pages":"2533-2540"},"PeriodicalIF":4.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142822557","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Psychological distress over 12 months post-diagnosis in an early inflammatory arthritis cohort.","authors":"Lucy Zhao, James Galloway, Jo Ledingham, Sarah Gallagher, Gerasimina Garnavos, Paul Amlani-Hatcher, Nicky Wilson, Lewis Carpenter, Kirsty Bannister, Sam Norton","doi":"10.1093/rheumatology/keae276","DOIUrl":"10.1093/rheumatology/keae276","url":null,"abstract":"<p><strong>Objectives: </strong>People with inflammatory arthritis (IA) experience worsened mental wellbeing alongside disease progression. Using the National Early Inflammatory Arthritis Audit (NEIAA), we assessed trends in psychological distress during the 12 months following IA diagnosis, mapping these against clinical outcomes to identify associations.</p><p><strong>Methods: </strong>This is a prospective study of people recruited to NEIAA receiving an IA diagnosis and completing the baseline patient survey. Patient-reported outcomes (PROs) at baseline, 3 months and 12 months were collected, including psychological distress [assessed using Patient Health Questionnaire Anxiety and Depression Screener (PHQ4ADS)]. Mixed effects linear regression models estimated associations between predictor variables with psychological distress at baseline and over time.</p><p><strong>Results: </strong>Of 6873 eligible patients, 3451 (50.2%) showed psychological distress at baseline. Of those completing follow-ups, 30.0% and 24.1% were distressed at 3 months and 12 months, respectively. Higher psychological distress at diagnosis was more commonly reported by younger, female and non-White patients. Clinical factors, including higher counts of comorbidities, prior depression and higher disease activity at diagnosis were associated with higher distress. Higher distress at baseline was associated with poorer outcomes over time in quality of life, disability, work performance, disease activity, as well as reduced likelihood of achieving good treatment response by EULAR criteria.</p><p><strong>Conclusion: </strong>Half of patients with IA show significant mental health comorbidity at presentation, which associated with worse disease outcomes and quality of life. Screening for anxiety and depression should be a universal standard, and access to effective mood therapies alongside arthritis treatments is essential. Strategies should be culturally valid and consider multi-morbidities.</p>","PeriodicalId":21255,"journal":{"name":"Rheumatology","volume":" ","pages":"2469-2478"},"PeriodicalIF":4.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12048071/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140945919","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 to: Non-adherence to urate lowering therapy in gout after 5 years is related to poor outcomes: results from the NOR-Gout study.","authors":"","doi":"10.1093/rheumatology/keae719","DOIUrl":"10.1093/rheumatology/keae719","url":null,"abstract":"","PeriodicalId":21255,"journal":{"name":"Rheumatology","volume":" ","pages":"3171"},"PeriodicalIF":4.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12048057/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143773250","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":"Association between colchicine use and adverse cardiovascular events in patients with gout: a nationwide nested case-control study.","authors":"Hyung Woo Kim, Minjin Kang, Hyunsun Lim, Cheol Ho Park, Jae Young Kim, Tae Ik Chang, Seung Hyeok Han","doi":"10.1093/rheumatology/keae545","DOIUrl":"10.1093/rheumatology/keae545","url":null,"abstract":"<p><strong>Objective: </strong>The association between colchicine use and the primary prevention of atherosclerotic cardiovascular disease (ASCVD) remains unknown. This study aimed to explore the association between colchicine use and new development of ASCVD and ASCVD-related mortality in patients with incident gout.</p><p><strong>Methods: </strong>This nested case-control study utilized the nationwide claims database of the Korean National Health Insurance System. Patients without a history of ASCVD who developed incident gout and were newly started on allopurinol as first-line therapy between 2011 and 2016 were initially screened. Individuals who experienced ASCVD event or ASCVD-related mortality during the follow-up period were matched with four controls for age, sex, income, residential area, co-morbidities and medications. The main exposure was colchicine use, assessed by (i) the cumulative defined daily doses (cDDDs) and (ii) the cumulative duration. For secondary analyses, the risk of ASCVD events and ASCVD-related mortality were examined separately.</p><p><strong>Results: </strong>Overall, 9346 patients with ASCVD event or ASCVD-related mortality were matched with 35 070 controls. The patient population was predominantly male. Compared with non-users, a curvilinear relationship between higher cDDDs of colchicine and the odds of ASCVD event was observed; the odds ratios (95% CI) were 1.09 (1.04, 1.15) for <90 cDDDs, 1.20 (1.07, 1.33) for 80-179 cDDDs and 1.21 (1.09, 1.35) for ≥180 cDDDs. This association was similarly observed for ASCVD events and ASCVD-related mortality.</p><p><strong>Conclusion: </strong>Colchicine use was associated with an increased risk of ASCVD in patients with newly diagnosed gout who did not have a prior history of ASCVD.</p>","PeriodicalId":21255,"journal":{"name":"Rheumatology","volume":" ","pages":"2601-2608"},"PeriodicalIF":4.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142406742","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Manubriosternal joint destruction with a rheumatoid nodule in rheumatoid arthritis.","authors":"Takeshi Zoshima","doi":"10.1093/rheumatology/keaf080","DOIUrl":"10.1093/rheumatology/keaf080","url":null,"abstract":"","PeriodicalId":21255,"journal":{"name":"Rheumatology","volume":" ","pages":"3220-3221"},"PeriodicalIF":4.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143399892","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Have we found a true disease-modifying osteoarthritis drug (DMOAD) or is there still much work to be done?","authors":"Roy Fleischmann","doi":"10.1093/rheumatology/keaf031","DOIUrl":"10.1093/rheumatology/keaf031","url":null,"abstract":"","PeriodicalId":21255,"journal":{"name":"Rheumatology","volume":" ","pages":"2345-2346"},"PeriodicalIF":4.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143468878","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prescribing habits before and after regulation change: a British perspective.","authors":"Ben Mulhearn, Marwan Bukhari","doi":"10.1093/rheumatology/keae713","DOIUrl":"10.1093/rheumatology/keae713","url":null,"abstract":"","PeriodicalId":21255,"journal":{"name":"Rheumatology","volume":" ","pages":"2341-2342"},"PeriodicalIF":4.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142877766","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neutrophil-to-lymphocyte ratio as a biomarker for clinical response after autologous haematopoietic stem cell transplantation in systemic sclerosis.","authors":"Shiri Keret, Lisa Kaly, George Schett, Christina Bergmann, Erik Feldman, Tsila Zuckerman, Dana Yehudai-Ofir, Aniela Shouval, Abid Awisat, Itzhak Rosner, Michael Rozenbaum, Nina Boulman, Alaa Sawaed, Emilia Hardak, Jörg Henes, Gleb Slobodin, Doron Rimar","doi":"10.1093/rheumatology/keae606","DOIUrl":"10.1093/rheumatology/keae606","url":null,"abstract":"<p><strong>Objective: </strong>SSc is a complex disease that affects various target organs, making it difficult to assess response and determine remission or relapse. A baseline neutrophil-to-lymphocyte ratio (NLR) >2.95 is associated with severe progressive skin and lung disease and decreased 5-year survival in SSc. However, it is unknown whether NLR changes in response to treatment. To retrospectively evaluate NLR changes as a biomarker for treatment response in SSc.</p><p><strong>Methods: </strong>Progressive diffuse SSc patients who were treated with autologous haematopoietic stem cell transplantation (AHSCT group), with combination therapy of rituximab and MMF (combination group) or chimeric antigen receptor-T-cell (CAR-T) therapy group, were recruited along with healthy controls (HC group). NLR, modified Rodnan Skin Score (mRSS) and forced vital capacity (FVC)% predicted were repeatedly assessed over 2 years.</p><p><strong>Results: </strong>Fifteen patients were recruited in the AHSCT group, 15 in the combination group and 6 patients in the CAR-T group. Baseline mean NLR was high (>2.95) in AHSCT, combination groups and CAR-T compared with HC. All treatment arms showed a statistically significant decrease in mRSS values and an increase in FVC% at each time point up to 12 months. In a linear mixed model, NLR significantly decreased up to 24 months only in the AHSCT group. NLR correlated with mRSS and FVC exclusively in the AHSCT group. NLR increased above 3 in two patients who experienced a relapse after AHSCT.</p><p><strong>Conclusion: </strong>NLR is a simple biomarker that correlated with outcome measures in SSc following AHSCT but not with conventional therapy or CAR-T therapy. It is suggested that a decrease in NLR following AHSCT may indicate remission, whereas an increase may be associated with exacerbation. Further research is needed to validate these novel findings.</p>","PeriodicalId":21255,"journal":{"name":"Rheumatology","volume":" ","pages":"3160-3165"},"PeriodicalIF":4.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142562769","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Executive Summary: The British Society for Rheumatology guideline for the management of foot health in inflammatory arthritis.","authors":"Lara S Chapman, Michael Backhouse, Nadia Corp, Danielle van der Windt, Lindsay Bearne, Lindsey Cherry, Gavin Cleary, Jasmine Davey, Rachel Ferguson, Philip Helliwell, Adam Lomax, Helen McKeeman, Alan A Rawlings, Robin Rees, Robbie Rooney, Sarah Ryan, Lucy Sanders, Heidi J Siddle, Sue Varley, Louise Warburton, Jim Woodburn, Edward Roddy","doi":"10.1093/rheumatology/keaf072","DOIUrl":"10.1093/rheumatology/keaf072","url":null,"abstract":"","PeriodicalId":21255,"journal":{"name":"Rheumatology","volume":" ","pages":"2347-2354"},"PeriodicalIF":4.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12048049/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143658492","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}