Lancet Rheumatology最新文献

{"title":"CD19-targeting CAR-T cell treatment in patients with diffuse systemic sclerosis","authors":"Jérôme Avouac","doi":"10.1016/S2665-9913(24)00311-4","DOIUrl":"10.1016/S2665-9913(24)00311-4","url":null,"abstract":"","PeriodicalId":48540,"journal":{"name":"Lancet Rheumatology","volume":"7 2","pages":"Pages e74-e75"},"PeriodicalIF":15.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142630663","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-targeting CAR T-cell therapy in patients with diffuse systemic sclerosis: a case series","authors":"Janina Auth MD ,&nbsp;Fabian Müller PD MD ,&nbsp;Simon Völkl PD ,&nbsp;Nadine Bayerl MD ,&nbsp;Prof Jörg H W Distler MD ,&nbsp;Carlo Tur MD ,&nbsp;Maria G Raimondo MD ,&nbsp;Sara Chenguiti Fakhouri MS ,&nbsp;Armin Atzinger MD ,&nbsp;Birte Coppers MS ,&nbsp;Markus Eckstein PD ,&nbsp;Anna-Maria Liphardt PD ,&nbsp;Prof Tobias Bäuerle MD ,&nbsp;Koray Tascilar MD ,&nbsp;Michael Aigner PD ,&nbsp;Sascha Kretschmann PhD ,&nbsp;Andreas Wirsching MD ,&nbsp;Jule Taubmann MD ,&nbsp;Melanie Hagen MD ,&nbsp;Andrea-Hermina Györfi MD ,&nbsp;Christina Bergmann MD","doi":"10.1016/S2665-9913(24)00282-0","DOIUrl":"10.1016/S2665-9913(24)00282-0","url":null,"abstract":"<div><h3>Background</h3><div>CD19-targeting chimeric antigen receptor (CAR) T-cell therapy has shown remarkable outcomes in patients with systemic lupus erythematosus. The effects of CD19-targeting CAR T cells on organ manifestations in patients with systemic sclerosis have yet to be characterised. B cells have a central role in the pathogenesis of systemic sclerosis. We present a detailed analysis of the effects of CD19-targeting CAR T-cell therapy in patients with systemic sclerosis.</div></div><div><h3>Methods</h3><div>Six patients with severe diffuse systemic sclerosis with an insufficient response to at least two treatments were consecutively recruited at the Department of Internal Medicine 3, University Hospital Erlangen (Erlangen, Germany) to receive CD19-targeting CAR T-cell treatment (1 × 10⁶ CAR T cells per kg bodyweight). Events were predefined by progression of interstitial lung disease, onset of congestive heart failure, onset of renal failure, onset of arterial hypertension, or initiation of new immunosuppressive or antifibrotic therapy. Event-free time or treatment intensification after study entry was the primary outcome. Key secondary outcomes included changes in the modified Rodnan Skin Score (mRSS), imaging (a component of the assessment of lung fibrosis), laboratory assessments, patient-reported outcomes, and a modified version of the American College of Rheumatology Composite Response Index in Systemic Sclerosis (ACR-CRISS), assessed at baseline, 3 months, 6 months, 9 months, and 12 months.</div></div><div><h3>Findings</h3><div>Between April 20, 2022, and Nov 8, 2023, six patients with severe diffuse systemic sclerosis (median age 42 years [IQR 36–53]; four men and two women; all White European) were recruited and received CD19-targeted CAR T-cell therapy. The median follow-up time was 487 days (IQR 342–585). No events occurred within the observational period. Probability of improvement in the ACR-CRISS score increased to a median of 100% (IQR 100–100) at 6 months. Median mRSS decreased by 31% (IQR 29–38), corresponding to a median of 8 points (IQR 7–13) within 100 days. The extent of disease on CT scan decreased by a median of 4% (IQR 3–4) due to reduction of ground-glass opacities while the reticular pattern remained stable. Forced vital capacity improved by a median of 195 mL (IQR 18–275) at the latest observational timepoint.</div></div><div><h3>Interpretation</h3><div>We provide the first evidence that CD19-targeting CAR T-cell therapy might intercept with the progression of fibrotic organ manifestations in patients with systemic sclerosis.</div></div><div><h3>Funding</h3><div>Deutsche Forschungsgemeinschaft, Deutsche Krebshilfe, ELAN-Foundation Erlangen, IZKF Erlangen, and Bundesministerium für Bildung und Forschung.</div></div>","PeriodicalId":48540,"journal":{"name":"Lancet Rheumatology","volume":"7 2","pages":"Pages e83-e93"},"PeriodicalIF":15.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142630661","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}

{"title":"The inclusion of Indigenous voices in health research","authors":"Katherine A Collins","doi":"10.1016/S2665-9913(24)00335-7","DOIUrl":"10.1016/S2665-9913(24)00335-7","url":null,"abstract":"","PeriodicalId":48540,"journal":{"name":"Lancet Rheumatology","volume":"7 2","pages":"Pages e75-e76"},"PeriodicalIF":15.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142796396","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":"Coronary polyarteritis nodosa in a young adult","authors":"Michele Marchini","doi":"10.1016/S2665-9913(24)00397-7","DOIUrl":"10.1016/S2665-9913(24)00397-7","url":null,"abstract":"","PeriodicalId":48540,"journal":{"name":"Lancet Rheumatology","volume":"7 2","pages":"Page e79"},"PeriodicalIF":15.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142967129","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":"Older age and frailty in ANCA-associated vasculitis: the thin line between undertreating and overtreating","authors":"Sara Thietart ,&nbsp;Xavier Puéchal","doi":"10.1016/S2665-9913(24)00399-0","DOIUrl":"10.1016/S2665-9913(24)00399-0","url":null,"abstract":"","PeriodicalId":48540,"journal":{"name":"Lancet Rheumatology","volume":"7 2","pages":"Page e80"},"PeriodicalIF":15.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143068858","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":"Research in Brief","authors":"Jennifer Thorley","doi":"10.1016/S2665-9913(25)00003-7","DOIUrl":"10.1016/S2665-9913(25)00003-7","url":null,"abstract":"","PeriodicalId":48540,"journal":{"name":"Lancet Rheumatology","volume":"7 2","pages":"Page e82"},"PeriodicalIF":15.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143128191","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":"Advancing personalised precision treatment for Still's disease based on molecular characteristics and disease progression","authors":"Yujie Shen MM ,&nbsp;Jinchao Jia MD ,&nbsp;Jialin Teng MD ,&nbsp;Prof Chengde Yang MD ,&nbsp;Qiongyi Hu MD","doi":"10.1016/S2665-9913(24)00225-X","DOIUrl":"10.1016/S2665-9913(24)00225-X","url":null,"abstract":"<div><div>Still's disease, a systemic autoinflammatory disorder with a classic multigenetic background, is characterised by polyarthritis, high-spiking fever, salmon-like evanescent skin rash, and hyperferritinaemia. Although the exact cause of Still's disease remains unclear, it is believed to be influenced by genetic factors, infections, and immune dysregulation. Current studies indicate that neutrophils and macrophages play crucial roles in the pathogenesis of Still's disease, along with involvement of natural killer cells, T cells, and B cells. Advances in biologic agents have expanded treatment strategies beyond conventional approaches, with cytokine-targeted agents showing promise in the management of Still's disease. Some cytokine-targeting biologic agents can be developed based on clinical manifestations, complications, immune cells, and molecular networks. Emphasis of immunophenotyping for precise clinical subtyping and targeted molecular therapies based on these findings is crucial for optimising treatment outcomes. In this Review, we discuss the latest advancements in the understanding of Still's disease pathogenesis and corresponding therapeutic approaches.</div></div>","PeriodicalId":48540,"journal":{"name":"Lancet Rheumatology","volume":"7 2","pages":"Pages e127-e140"},"PeriodicalIF":15.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142478078","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 apremilast on hand and whole-body MRI assessments of inflammation in patients with psoriatic arthritis (MOSAIC): a phase 4, multicentre, single-arm, open-label study","authors":"Prof Mikkel Østergaard MD ,&nbsp;Mikael Boesen MD ,&nbsp;Walter P Maksymowych FRCP ,&nbsp;Robert G Lambert FRCPC ,&nbsp;Michael R Bubb MD ,&nbsp;Olga Kubassova PhD ,&nbsp;Guillermo Valenzuela MD ,&nbsp;Jyotsna Reddy MD ,&nbsp;Stephen Colgan PhD ,&nbsp;Yuri Klyachkin PhD ,&nbsp;Cynthia Deignan PhD ,&nbsp;Zhenwei Zhou PhD ,&nbsp;Hamid Amouzadeh PhD ,&nbsp;Philip J Mease MD","doi":"10.1016/S2665-9913(24)00232-7","DOIUrl":"10.1016/S2665-9913(24)00232-7","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;The Psoriatic Arthritis Magnetic Resonance Imaging Scoring System (PsAMRIS) and MRI Whole-Body Scoring System for Inflammation in Peripheral Joints and Entheses in Inflammatory Arthritis (MRI-WIPE) have not been used together to assess treatment of psoriatic arthritis in a clinical trial. We aimed to assess the effect of apremilast treatment on inflammation, with outcomes measured by PsAMRIS and MRI-WIPE.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;MOSAIC was a phase 4, multicentre, single-arm, open-label study conducted at 29 sites across ten countries (Belgium, Canada, Denmark, Germany, Italy, Russia, Spain, Switzerland, the UK, and the USA). Adults aged 18 years or older with a documented diagnosis of psoriatic arthritis for a duration of 3 months to 5 years self-enrolled and were included if they met the classification criteria for active psoriatic arthritis at screening. Patients were required to have at least three swollen and three tender joints with hand involvement and at least one active enthesitis site according to the Spondyloarthritis Research Consortium of Canada enthesitis index or the Leeds enthesitis index. Patients were excluded if they had previous treatment with a biological disease-modifying antirheumatic drug or previous treatment with more than two conventional synthetic disease-modifying antirheumatic drugs. After a 5-day titration period, patients received apremilast 30 mg orally twice per day. Concomitant stable methotrexate up to 25 mg per week was permitted. The primary endpoint was change from baseline to week 24 in a composite inflammation score of bone marrow oedema, synovitis, and tenosynovitis in the hand as assessed by PsAMRIS. The full analysis set and safety population included all enrolled patients who received at least one dose of apremilast. This completed study is registered with &lt;span&gt;&lt;span&gt;ClinicalTrials.gov&lt;/span&gt;&lt;svg&gt;&lt;path&gt;&lt;/path&gt;&lt;/svg&gt;&lt;/span&gt; (&lt;span&gt;&lt;span&gt;NCT03783026&lt;/span&gt;&lt;svg&gt;&lt;path&gt;&lt;/path&gt;&lt;/svg&gt;&lt;/span&gt;).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Findings&lt;/h3&gt;&lt;div&gt;Between Feb 6, 2019, and May 11, 2022, 123 patients were enrolled in the MOSAIC study. Of these 123 patients, 122 (99%) were treated with apremilast and included in the full analysis set and safety population. 67 (55%) of 122 patients were female, 55 (45%) were male, and 116 (95%) were White. 80 (66%) of 122 patients completed 48 weeks of treatment. The least squares mean change from baseline to week 24 in the composite inflammation score of bone marrow oedema, synovitis, and tenosynovitis as assessed by PsAMRIS was −2·32 (95% CI −4·73 to 0·09). 95 (78%) of 122 patients had at least one treatment-emergent adverse event. Six (5%) patients had a severe treatment-emergent adverse event and six (5%) patients had a serious treatment-emergent adverse event. No serious treatment-emergent adverse events were considered to be related to apremilast.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Interpretation&lt;/h3&gt;&lt;div&gt;Apremilast improved inflammation in joints and entheses on ","PeriodicalId":48540,"journal":{"name":"Lancet Rheumatology","volume":"7 2","pages":"Pages e118-e126"},"PeriodicalIF":15.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564720","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":"Faecal microbiota transplantation in patients with systemic sclerosis and lower gastrointestinal tract symptoms in Norway (ReSScue): a phase 2, randomised, double-blind, placebo-controlled trial.","authors":"Håvard Fretheim, Imon Barua, Gunnstein Bakland, Alvilde Dhainaut, Anne-Kristine Halse, Maylen N Carstens, Henriette Didriksen, Øyvind Midtvedt, Knut E A Lundin, Lars Aabakken, Vikas K Sarna, Hasse K Zaré, Dinesh Khanna, Oliver Distler, Tore Midtvedt, Espen S Bækkevold, Inge C Olsen, Diana Domanska, Maiju E Pesonen, Øyvind Molberg, Anna-Maria Hoffmann-Vold","doi":"10.1016/S2665-9913(24)00334-5","DOIUrl":"https://doi.org/10.1016/S2665-9913(24)00334-5","url":null,"abstract":"<p><strong>Background: </strong>Gastrointestinal tract involvement is highly prevalent in systemic sclerosis, with few treatment options. We assessed the efficacy and safety of faecal microbiota transplantation using standardised anaerobic cultivated human intestinal microbiome (ACHIM) as a novel treatment option for patients with systemic sclerosis and symptomatic lower gastrointestinal tract involvement.</p><p><strong>Methods: </strong>In this phase 2, randomised, double-blind, placebo-controlled trial done at four university hospitals in Norway, we enrolled adults aged 18-85 years with systemic sclerosis and moderate-to-severe lower gastrointestinal tract symptoms (bloating or diarrhoea). Participants were randomly assigned 1:1 to intestinal infusions of placebo or ACHIM at weeks 0 and 2, stratified by worst symptom (bloating or diarrhoea). The primary endpoint was change in worst lower gastrointestinal tract symptom (bloating or diarrhoea) from week 0 to week 12, measured using the University of California Los Angeles Scleroderma Clinical Trial Consortium Gastrointestinal Tract 2.0 scoring system in the intention-to-treat population. Safety was assessed at weeks 0, 2, 4, 6, and 12 in all participants who received at least one infusion. A person with lived experience of systemic sclerosis was involved in the study planning and conduct. This trial was registered at ClinicalTrials.gov, NCT04300426.</p><p><strong>Findings: </strong>Between Sept 24, 2020, and Jan 14, 2022, 67 participants were enrolled and randomly allocated to placebo (n=34) or ACHIM (n=33). Mean age was 58·91 years (SD 11·59). 62 (93%) of 67 participants were women, five (7%) were men, and 50 (75%) were anti-centromere antibody positive. Change in worst lower gastrointestinal tract symptom from week 0 to week 12 did not differ between participants who received ACHIM (-0·13, 95% CI -0·37 to 0·11) and participants who received placebo (-0·33, -0·57 to -0·09; average marginal effect 0·20, 95% CI -0·12 to 0·52; p=0·22). Adverse events, mostly mild and short-lived gastrointestinal tract symptoms, were reported by 16 (48%) of 33 participants in the ACHIM group and 19 (56%) of 34 in the placebo group. During gastroscopy, one participant had a duodenal perforation.</p><p><strong>Interpretation: </strong>Faecal microbiota transplantation with ACHIM was well tolerated in participants with systemic sclerosis but did not result in an improvement in lower gastrointestinal tract symptoms.</p><p><strong>Funding: </strong>KLINBEFORSK.</p><p><strong>Translation: </strong>For the Norwegian translation of the abstract see Supplementary Materials section.</p>","PeriodicalId":48540,"journal":{"name":"Lancet Rheumatology","volume":" ","pages":""},"PeriodicalIF":15.0,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143123765","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":"Is faecal microbiota transplantation ready for prime time in systemic sclerosis?","authors":"Shu Wen Tay, Andrea Hsiu Ling Low","doi":"10.1016/S2665-9913(24)00376-X","DOIUrl":"https://doi.org/10.1016/S2665-9913(24)00376-X","url":null,"abstract":"","PeriodicalId":48540,"journal":{"name":"Lancet Rheumatology","volume":" ","pages":""},"PeriodicalIF":15.0,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143123780","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}