Annals of the Rheumatic Diseases最新文献

{"title":"More than meets the eye.","authors":"Elise Siegert, Werner Stenzel, David Sinan Koca, Gerhard Krönke, Robert Biesen","doi":"10.1136/ard-2024-226168","DOIUrl":"10.1136/ard-2024-226168","url":null,"abstract":"","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":"84 1","pages":"150-151"},"PeriodicalIF":20.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143057833","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":"Performance analysis of a deep-learning algorithm to detect the presence of inflammation in MRI of sacroiliac joints in patients with axial spondyloarthritis.","authors":"Joeri Nicolaes, Evi Tselenti, Theodore Aouad, Clementina López-Medina, Antoine Feydy, Hugues Talbot, Bengt Hoepken, Natasha de Peyrecave, Maxime Dougados","doi":"10.1136/ard-2024-225862","DOIUrl":"10.1136/ard-2024-225862","url":null,"abstract":"<p><strong>Objectives: </strong>To assess the ability of a previously trained deep-learning algorithm to identify the presence of inflammation on MRI of sacroiliac joints (SIJ) in a large external validation set of patients with axial spondyloarthritis (axSpA).</p><p><strong>Methods: </strong>Baseline SIJ MRI scans were collected from two prospective randomised controlled trials in patients with non-radiographic (nr-) and radiographic (r-) axSpA (RAPID-axSpA: NCT01087762 and C-OPTIMISE: NCT02505542) and were centrally evaluated by two expert readers (and adjudicator in case of disagreement) for the presence of inflammation by the 2009 Assessment of SpondyloArthritis International Society (ASAS) definition. Scans were processed by the deep-learning algorithm, blinded to clinical information and central expert readings.</p><p><strong>Results: </strong>Pooling the patients from RAPID-axSpA (n=152) and C-OPTIMISE (n=579) yielded a validation set of 731 patients (mean age: 34.2 years, SD: 8.6; 505/731 (69.1%) male), of which 326/731 (44.6%) had nr-axSpA and 436/731 (59.6%) had inflammation on MRI per central readings. Scans were obtained from over 30 scanners from 5 manufacturers across over 100 clinical sites. Comparing the trained algorithm with the human central readings yielded a sensitivity of 70% (95% CI 66% to 73%), specificity of 81% (95% CI 78% to 84%), positive predictive value of 84% (95% CI 82% to 87%), negative predictive value of 64% (95% CI 61% to 68%), Cohen's kappa of 0.49 (95% CI 0.43 to 0.55) and absolute agreement of 74% (95% CI 72% to 77%).</p><p><strong>Conclusion: </strong>The algorithm enabled acceptable detection of inflammation according to the 2009 ASAS MRI definition in a large external validation cohort.</p>","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":"84 1","pages":"60-67"},"PeriodicalIF":20.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143057836","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":"Bridging the gap: tackling the challenge of limited progressors in clinical trials aimed at slowing the transition from early preradiographic to established osteoarthritis.","authors":"Francis Berenbaum, Marc Buyse","doi":"10.1016/j.ard.2025.01.002","DOIUrl":"https://doi.org/10.1016/j.ard.2025.01.002","url":null,"abstract":"","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":"84 1","pages":"5-8"},"PeriodicalIF":20.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143057679","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":"Predicting rapid progression in knee osteoarthritis: a novel and interpretable automated machine learning approach, with specific focus on young patients and early disease.","authors":"Simone Castagno, Mark Birch, Mihaela van der Schaar, Andrew McCaskie","doi":"10.1136/ard-2024-225872","DOIUrl":"10.1136/ard-2024-225872","url":null,"abstract":"<p><strong>Objectives: </strong>To facilitate the stratification of patients with osteoarthritis (OA) for new treatment development and clinical trial recruitment, we created an automated machine learning (autoML) tool predicting the rapid progression of knee OA over a 2-year period.</p><p><strong>Methods: </strong>We developed autoML models integrating clinical, biochemical, X-ray and MRI data. Using two data sets within the OA Initiative-the Foundation for the National Institutes of Health OA Biomarker Consortium for training and hold-out validation, and the Pivotal Osteoarthritis Initiative MRI Analyses study for external validation-we employed two distinct definitions of clinical outcomes: Multiclass (categorising OA progression into pain and/or radiographic) and binary. Key predictors of progression were identified through advanced interpretability techniques, and subgroup analyses were conducted by age, sex and ethnicity with a focus on early-stage disease.</p><p><strong>Results: </strong>Although the most reliable models incorporated all available features, simpler models including only clinical variables achieved robust external validation performance, with area under the precision-recall curve (AUC-PRC) 0.727 (95% CI: 0.726 to 0.728) for multiclass predictions; and AUC-PRC 0.764 (95% CI: 0.762 to 0.766) for binary predictions. Multiclass models performed best in patients with early-stage OA (AUC-PRC 0.724-0.806) whereas binary models were more reliable in patients younger than 60 (AUC-PRC 0.617-0.693). Patient-reported outcomes and MRI features emerged as key predictors of progression, though subgroup differences were noted. Finally, we developed web-based applications to visualise our personalised predictions.</p><p><strong>Conclusions: </strong>Our novel tool's transparency and reliability in predicting rapid knee OA progression distinguish it from conventional 'black-box' methods and are more likely to facilitate its acceptance by clinicians and patients, enabling effective implementation in clinical practice.</p>","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":"84 1","pages":"124-135"},"PeriodicalIF":20.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143057838","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":"CD19-CAR T-cell therapy induces deep tissue depletion of B cells.","authors":"Carlo Tur, Markus Eckstein, Joachim Velden, Simon Rauber, Christina Bergmann, Janina Auth, Laura Bucci, Giulia Corte, Melanie Hagen, Andreas Wirsching, Ricardo Grieshaber-Bouyer, Petra Reis, Nicolai Kittan, Jochen Wacker, Aleix Rius Rigau, Andreas Ramming, Maria-Antonietta D'Agostino, Arndt Hartmann, Fabian Müller, Andreas Mackensen, Aline Bozec, Georg Schett, Maria Gabriella Raimondo","doi":"10.1136/ard-2024-226142","DOIUrl":"10.1136/ard-2024-226142","url":null,"abstract":"<p><strong>Objectives: </strong>CD19-targeting chimeric antigen receptor (CAR) T-cell therapy can induce long-term drug-free remission in patients with autoimmune diseases (AIDs). The efficacy of CD19-CAR T-cell therapy is presumably based on deep tissue depletion of B cells; however, such effect has not been proven in humans in vivo.</p><p><strong>Methods: </strong>Sequential ultrasound-guided inguinal lymph node biopsies were performed at baseline and after CD19-CAR T-cell therapy in patients with AIDs. Results were compared with lymph node biopsies from rituximab (RTX)-treated AID patients with absence of peripheral B cells. Conventional and immunohistochemistry staining were performed on lymph node tissue to assess architecture as well the number of B cells, follicular dendritic cells (FDCs), plasma cells, T cells and macrophages.</p><p><strong>Results: </strong>Sequential lymph node biopsies were analysed from five patients with AID before and after CD19-CAR T-cell therapy and from five patients with AID after RTX treatment. In addition, non-lymphoid organ biopsies (colon, kidney and gallbladder) from three additional patients with AID after CD19-CAR T-cell therapy were analysed. CD19⁺ and CD20⁺ B cells were completely depleted in the lymph nodes after CD19-CAR T-cell therapy, but not after RTX treatment. Plasma cells, T cells and macrophages in the lymph nodes remained unchanged. Follicular structures were disrupted and FDCs were depleted in the lymph nodes after CD19-CAR T-cell therapy, but not after RTX. Non-lymphoid organs were completely depleted of B cells.</p><p><strong>Discussion: </strong>This study demonstrates complete B-cell depletion in secondary lymphoid tissues of patients with AIDs following CD19-CAR T-cell therapy combined with standard lymphodepleting therapy.</p>","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":"84 1","pages":"106-114"},"PeriodicalIF":20.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143057683","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":"Results from the international collaborative systematic literature review informing the 2023 EULAR recommendations for the treatment of systemic sclerosis.","authors":"Alain Lescoat, Eugenia Bertoldo, Jelena Čolić, Tania Santiago, Yossra A Suliman, Jenny Emmel, Philip G Conaghan, Yannick Allanore, Francesco Del Galdo","doi":"10.1136/ard-2024-226429","DOIUrl":"10.1136/ard-2024-226429","url":null,"abstract":"<p><strong>Background: </strong>The EULAR recommendations for the treatment of systemic sclerosis (SSc) were updated in 2017, informed by a systematic literature review (SLR) completed in 2014.</p><p><strong>Objectives: </strong>The aim of this new SLR was to provide the most up-to-date literature to underpin contemporary EULAR recommendations for the management of SSc.</p><p><strong>Methods: </strong>30 searches for 30 interventions (including several outcomes/clinical questions), and 1 dedicated search (with several interventions) for calcinosis were prioritised by the task force. Three types of questions were defined: type I questions, unchanged as compared with the previous recommendations; type II questions exploring interventions already mentioned in the previous recommendations but with new outcomes; type III questions for new interventions.</p><p><strong>Results: </strong>14 490 abstracts were retrieved from the databases on 31 March 2022 and 2021 abstracts were retrieved on 11 October 2022. 483 new full texts were evaluated and 172 new articles were included for the first search and 9 for the second search. The majority of the questions covered by this SLR explored new interventions (40% of type III questions) or new outcomes (26% of type II questions). New interventions included targeted therapies such as abatacept, Janus kinase inhibitors or nintedanib, and updated questions incorporated the results from key game- changing randomised controlled trials including trials on tocilizumab, mycophenolate or rituximab in SSc- interstitial lung disease.</p><p><strong>Conclusions: </strong>This SLR provides and summarises the highest level of evidence for the new EULAR recommendations for the treatment of SSc, providing an unprecedented comprehensive overview of recent knowledge on SSc treatments and participating in defining the future research agenda.</p>","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":"84 1","pages":"77-92"},"PeriodicalIF":20.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143057840","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":"Greetings from the Editor - 2025.","authors":"Josef Smolen","doi":"10.1016/j.ard.2025.01.001","DOIUrl":"https://doi.org/10.1016/j.ard.2025.01.001","url":null,"abstract":"","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":"84 1","pages":"1-4"},"PeriodicalIF":20.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143057828","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":"Association of methotrexate polyglutamates concentration with methotrexate efficacy and safety in patients with rheumatoid arthritis treated with predefined dose: results from the MIRACLE trial.","authors":"Hiroya Tamai, Kei Ikeda, Toshiaki Miyamoto, Hiroaki Taguchi, Chang-Fu Kuo, Kichul Shin, Shintaro Hirata, Yutaka Okano, Shinji Sato, Hidekata Yasuoka, Masataka Kuwana, Tomonori Ishii, Hideto Kameda, Toshihisa Kojima, Yurie Nishi, Masahiko Mori, Hideaki Miyagishi, Genta Toshima, Yasunori Sato, Wen-Chan Tsai, Tsutomu Takeuchi, Yuko Kaneko","doi":"10.1136/ard-2024-226350","DOIUrl":"10.1136/ard-2024-226350","url":null,"abstract":"<p><strong>Objectives: </strong>The usefulness of methotrexate-polyglutamates (MTX-PGs) concentration for management of rheumatoid arthritis has been debated. We aimed to clarify the association of MTX-PGs concentration with efficacy and safety in MTX-naïve patients initiating MTX in a prospective interventional clinical trial.</p><p><strong>Methods: </strong>The MIRACLE trial enrolled 300 MTX-naïve patients. Oral MTX was initiated and increased to the maximum tolerated dose by week 12. Patients who did not achieve remission according to the Simplified Disease Activity Index at week 24 were randomised to either the continued dose or reduced dose group and were started on subcutaneous adalimumab. We measured the concentrations of MTX-PGs in erythrocytes using liquid chromatography-tandem mass spectrometry and analysed the association of these concentrations with efficacy and safety.</p><p><strong>Results: </strong>The mean concentration of total MTX-PGs increased with an increasing dose of MTX and continued to elevate for another 12 weeks after the dose was fixed. At week 24, the total MTX-PGs concentration was 110.5 (SD 43.8) nmol/L with MTX dose of 12.6 (3.0) mg/week (0.23 (0.07) mg/kg/week). During MTX monotherapy, the higher MTX-PGs concentration was an independent factor for lower disease activity; however, this association disappeared after adalimumab initiation in patients with continued MTX dose. Hepatotoxicity was related to the higher MTX-PGs concentration regardless of adalimumab use. The total MTX-PGs concentration was significantly elevated by lower estimated glomerular filtration rate, serum albumin and body mass index.</p><p><strong>Conclusions: </strong>The MIRACLE trial demonstrated that higher total MTX-PGs concentration in erythrocytes is related to the higher efficacy and lower safety of MTX.</p><p><strong>Trial registration number: </strong>NCT03505008.</p>","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":"84 1","pages":"41-48"},"PeriodicalIF":20.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143057654","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":"Therapeutic interception in individuals at risk of rheumatoid arthritis to prevent clinically impactful disease.","authors":"Kevin D Deane, V Michael Holers, Paul Emery, Kulveer Mankia, Hani El-Gabalawy, Jeffrey A Sparks, Karen H Costenbader, Georg Schett, Annette van der Helm-van Mil, Dirkjan van Schaardenburg, Ranjeny Thomas, Andrew P Cope","doi":"10.1136/ard-2023-224211","DOIUrl":"10.1136/ard-2023-224211","url":null,"abstract":"<p><p>Multiple clinical trials for rheumatoid arthritis (RA) prevention have been completed. Here, we set out to report on the lessons learnt from these studies. Researchers who conducted RA prevention trials shared the background, rationale, approach and outcomes and evaluated the lessons learnt to inform the next generation of RA prevention trials. Individuals at risk of RA can be identified through population screening, referrals to musculoskeletal programmes and by recognition of arthralgia suspicious for RA. Clinical trials in individuals at risk for future clinical RA have demonstrated that limited courses of corticosteroids, atorvastatin and hydroxychloroquine do not alter incidence rates of clinical RA; however, rituximab delays clinical RA onset, and methotrexate has transient effects in individuals who are anticitrullinated protein antibody-positive with subclinical joint inflammation identified by imaging. Abatacept delays clinical RA onset but does not fully prevent onset of RA after treatment cessation. Additionally, subclinical joint inflammation and symptoms appear responsive to interventions such as methotrexate and abatacept. To advance prevention, next steps include building networks of individuals at risk for RA, to improve risk stratification for future RA and to understand the biological mechanisms of RA development, including potential endotypes of disease, which can be targeted for prevention, thus adopting a more precision-based approach. Future trials should focus on interceptions aimed at preventing clinical RA onset and which treat existing symptoms and imaging-defined subclinical inflammation. These trials may include advanced designs (eg, adaptive) and should be combined with mechanistic studies to further define pathophysiological drivers of disease development.</p>","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":"84 1","pages":"14-28"},"PeriodicalIF":20.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143057841","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":"Microbiome research in autoimmune and immune-mediated inflammatory diseases: lessons, advances and unmet needs.","authors":"Jose U Scher, Renuka Nayak, Jose C Clemente","doi":"10.1136/ard-2024-225735","DOIUrl":"10.1136/ard-2024-225735","url":null,"abstract":"<p><p>The increasing prevalence of autoimmune and immune-mediated diseases (AIMDs) underscores the need to understand environmental factors that contribute to their pathogenesis, with the microbiome emerging as a key player. Despite significant advancements in understanding how the microbiome influences physiological and inflammatory responses, translating these findings into clinical practice remains challenging. This viewpoint reviews the progress and obstacles in microbiome research related to AIMDs, examining molecular techniques that enhance our understanding of microbial contributions to disease. We discuss significant discoveries linking specific taxa and metabolites to diseases such as rheumatoid arthritis, systemic lupus erythematosus and spondyloarthritis, highlighting the role of gut dysbiosis and host-microbiome interactions. Furthermore, we explore the potential of microbiome-based therapeutics, including faecal microbiota transplantation and pharmacomicrobiomics, while addressing the challenges of identifying robust microbial targets. We advocate for integrative, transdisease studies and emphasise the need for diverse cohort research to generalise findings across populations. Understanding the microbiome's role in AIMDs will pave the way for personalised medicine and innovative therapeutic strategies.</p>","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":"84 1","pages":"9-13"},"PeriodicalIF":20.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11822223/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143057831","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}