Lancet Rheumatology最新文献

{"title":"Sarilumab in relapsing polymyalgia rheumatica: patient-reported outcomes from a phase 3, double-blind, randomised controlled trial.","authors":"Vibeke Strand, Jerome Msihid, Jennifer Sloane, Michael C Nivens, Jingdong Chao, Angeliki Giannelou, Stefano Fiore, Lita Araujo, Bhaskar Dasgupta","doi":"10.1016/S2665-9913(25)00041-4","DOIUrl":"https://doi.org/10.1016/S2665-9913(25)00041-4","url":null,"abstract":"<p><strong>Background: </strong>Sarilumab is approved for adult patients with polymyalgia rheumatica who have had an inadequate response to corticosteroids or who cannot tolerate corticosteroid taper. We aimed to evaluate the effect of sarilumab on patient-reported outcomes.</p><p><strong>Methods: </strong>This phase 3, double-blind, randomised controlled trial was done in 60 centres in 17 countries. Eligible patients were adults aged 50 years or older who had at least one episode of disease flare during a glucocorticoid taper (at a dose of ≥7·5 mg per day or prednisone dose equivalent) within 12 weeks before screening and had a history of at least 8 weeks of glucocorticoid treatment (≥10 mg per day or prednisone dose equivalent). All the patients had symptoms of polymyalgia rheumatica and an erythrocyte sedimentation rate >30 mm/h or a C-reactive protein concentration of at least 10 mg/L within 12 weeks before screening. Patients were randomly assigned (1:1) to receive either subcutaneous sarilumab 200 mg once every 2 weeks with a 14-week glucocorticoid taper or matching placebo with a 52-week glucocorticoid taper. Patients and investigators were masked to treatment allocation. The patient-reported outcomes measured were Health Assessment Questionnaire Disability Index (HAQ-DI), Patient Global Assessment of Health Visual Analog Scale (VAS), Pain VAS, Short Form Health Survey (SF-36 v2), EuroQoL 5-Dimensions 3-Levels (EQ-5D including the descriptive system and the VAS), and Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F). Patient-reported outcomes were analysed until week 52 as changes from baseline. Post-hoc analyses included proportions of patients reporting improvements of at least minimum clinically important difference and scores of at least normative values. p values were nominal. Analyses were done in the intention-to-treat population. There was no involvement of people with lived experience at any stage of the study. This trial is registered with ClinicalTrials.gov, NCT03600818.</p><p><strong>Findings: </strong>Between Oct 9, 2018, and July 15, 2020, 118 patients were enrolled and randomly assigned to receive sarilumab (n=60) or placebo (n=58). Of these, 117 patients received treatment (59 in the sarilumab group and 58 in the placebo group). One patient assigned to the sarilumab group did not receive treatment. Mean age was 68·9 years (SD 8·1). 82 (69%) of 118 patients were female and 36 (31%) were male, and 98 (83%) were White. At baseline, moderate-to-severe fatigue was reported by 43 (73%) of 59 patients in the sarilumab group and 43 (74%) of 58 patients in the placebo group. At week 52, patients in the sarilumab group reported greater improvements than patients in the placebo group in SF-36 Physical Component Summary (PCS; least-squares mean [LSM] change 7·65 vs 2·87, p=0·020) and Mental Component Summary (MCS; 3·04 vs -1·71, p=0·030) scores, and in five of eight domains. Sarilumab showed greater improvements in EQ-","PeriodicalId":48540,"journal":{"name":"Lancet Rheumatology","volume":" ","pages":""},"PeriodicalIF":15.0,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144369436","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":"Polymyalgia rheumatica: killing them softly.","authors":"David Fl Liew, Claire E Owen","doi":"10.1016/S2665-9913(25)00095-5","DOIUrl":"https://doi.org/10.1016/S2665-9913(25)00095-5","url":null,"abstract":"","PeriodicalId":48540,"journal":{"name":"Lancet Rheumatology","volume":" ","pages":""},"PeriodicalIF":15.0,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144369435","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)00160-2","DOIUrl":"10.1016/S2665-9913(25)00160-2","url":null,"abstract":"","PeriodicalId":48540,"journal":{"name":"Lancet Rheumatology","volume":"7 7","pages":"Page e462"},"PeriodicalIF":15.0,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144297461","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":"Translating AI innovation into clinical practice","authors":"The Lancet Rheumatology","doi":"10.1016/S2665-9913(25)00161-4","DOIUrl":"10.1016/S2665-9913(25)00161-4","url":null,"abstract":"","PeriodicalId":48540,"journal":{"name":"Lancet Rheumatology","volume":"7 7","pages":"Page e451"},"PeriodicalIF":15.0,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144297353","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":"Exploring the specificity of MRI findings in rheumatoid arthritis.","authors":"Mami Tamai, Atsushi Kawakami","doi":"10.1016/S2665-9913(25)00131-6","DOIUrl":"https://doi.org/10.1016/S2665-9913(25)00131-6","url":null,"abstract":"","PeriodicalId":48540,"journal":{"name":"Lancet Rheumatology","volume":" ","pages":""},"PeriodicalIF":15.0,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144310555","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":"Comparison of findings on contrast-enhanced MRI of the hand, wrist, and forefoot in healthy controls, two at-risk groups, and patients with rheumatoid arthritis: a cohort study.","authors":"Dennis A Ton, Nikolet K den Hollander, Hanna W van Steenbergen, Annette H M van der Helm-van Mil","doi":"10.1016/S2665-9913(25)00065-7","DOIUrl":"https://doi.org/10.1016/S2665-9913(25)00065-7","url":null,"abstract":"<p><strong>Background: </strong>The sensitivity of MRI in detecting joint inflammation in rheumatoid arthritis is well known but its specificity is less discussed. It is important to prevent false positive results and consequent overdiagnosis. Therefore, we aimed to examine MRI-detected inflammation that is less specific for rheumatoid arthritis by evaluating the frequencies of inflammation in healthy controls and in two at-risk groups who have not developed rheumatoid arthritis, compared with patients with rheumatoid arthritis.</p><p><strong>Methods: </strong>In this cohort study, we performed contrast-enhanced MRIs of the second to fifth metacarpophalangeal, wrist, and first to fifth metatarsophalangeal joints of two at-risk groups (individuals with clinically suspect arthralgia and patients with undifferentiated arthritis who have not developed rheumatoid arthritis within a 2-year and 1-year follow-up period, respectively), and patients with rheumatoid arthritis, from two longitudinal observational cohort studies at Leiden University Medical Centre, Netherlands; the Leiden Early Arthritis Clinic (EAC) and the clinically suspect arthralgia (CSA) cohort. Healthy volunteers were also recruited as controls from Leiden University Medical Centre. MRIs were evaluated for synovitis, tenosynovitis, and osteitis using the Rheumatoid Arthritis MRI Scoring system. Intermetatarsal bursitis was also evaluated. All MRIs were scored by two readers independently of each other and who were blinded for clinical data. Each site was graded 0 (no inflammation), 1 (low), 2 (moderate), or 3 (severe). Increased signal intensity of joints, tendon sheaths, and bones were considered as less specific for rheumatoid arthritis if a similar signal intensity grade was present in more than 5% of the reference group. Comparisons were made in the following age-strata: <40 years, 40-59 years, and ≥60 years. Patient partners were involved in the design of the EAC and CSA cohorts.</p><p><strong>Findings: </strong>Participants with valid MRI data from the EAC cohort (enrolled Aug 24, 2010, to March 9, 2020]) and the CSA cohort (enrolled April 3, 2012, to April 29, 2021), and 193 healthy volunteers (enrolled between Nov 15, 2013, to Dec 2, 2014) were included. At follow-up, 516 patients had rheumatoid arthritis, 305 had undifferentiated arthritis, and 598 had clinically suspect arthralgia. Of all participants, 1089 (68%) of 1612 were female and 523 (32%) were male, 1105 (94%) of 1160 were White, and mean age was 51 years (SD 14). Grade 2 and 3 synovitis, tenosynovitis, or osteitis did not occur in more than 5% of healthy controls and clinically suspect arthralgia non-converters (of all ages), therefore grade 1 inflammation in these reference populations versus patients with rheumatoid arthritis was evaluated. Grade 1 inflammation was found at a number of sites in the hand, wrist, and forefoot in more than 5% in all reference populations across all age groups, and these locations of i","PeriodicalId":48540,"journal":{"name":"Lancet Rheumatology","volume":" ","pages":""},"PeriodicalIF":15.0,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144310554","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":"Hydroxychloroquine use in pregnant women with systemic lupus erythematosus: the pill that shields.","authors":"Grégoire Martin de Frémont, Gaëlle Guettrot-Imbert, Nathalie Costedoat-Chalumeau","doi":"10.1016/S2665-9913(25)00132-8","DOIUrl":"https://doi.org/10.1016/S2665-9913(25)00132-8","url":null,"abstract":"","PeriodicalId":48540,"journal":{"name":"Lancet Rheumatology","volume":" ","pages":""},"PeriodicalIF":15.0,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144295151","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":"Dual JAK and ROCK inhibition and comorbidities in rheumatoid arthritis.","authors":"Fabiola Atzeni, James Galloway","doi":"10.1016/S2665-9913(25)00111-0","DOIUrl":"https://doi.org/10.1016/S2665-9913(25)00111-0","url":null,"abstract":"","PeriodicalId":48540,"journal":{"name":"Lancet Rheumatology","volume":" ","pages":""},"PeriodicalIF":15.0,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144295148","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":"Dual JAK and ROCK inhibition with CPL'116 in patients with rheumatoid arthritis with inadequate response to methotrexate: a randomised, double-blind, placebo-controlled, phase 2 trial.","authors":"Maciej Wieczorek, Bartłomiej Kisiel, Dorota Włodarczyk, Piotr Leszczyński, Iryna V Kurylchyk, Ivan Vyshnyvetskyy, Izabela Kierzkowska, Piotr Pankiewicz, Michał Kaza, Martyna Banach, Joanna Kogut","doi":"10.1016/S2665-9913(25)00060-8","DOIUrl":"https://doi.org/10.1016/S2665-9913(25)00060-8","url":null,"abstract":"<p><strong>Background: </strong>Janus kinase (JAK) inhibitors are an effective treatment option in rheumatoid arthritis and other autoimmune diseases. However, the use of JAK inhibitors is associated with increased total cholesterol, LDL cholesterol, triglycerides, and creatinine kinase, reducing the net clinical benefit of using them. Adding Rho-associated protein kinase (ROCK) inhibition to JAK inhibition might provide cardioprotection as ROCK inhibitors have been shown to reduce vascular inflammation, improve endothelial function, and prevent cardiac remodelling in preclinical models. In this study we investigated CPL409116 (hereafter referred to as CPL'116), a novel dual JAK and ROCK inhibitor, in patients with rheumatoid arthritis with inadequate response to methotrexate, to assess dose-dependent effects on disease control, pharmacokinetics, and laboratory abnormalities among other safety events.</p><p><strong>Methods: </strong>This phase 2, randomised, double-blind, dose-ranging, placebo-controlled, parallel group trial enrolled patients aged 18-75 years at nine hospitals or clinics in Poland and Ukraine. Main inclusion criteria were a documented diagnosis of adult-onset, moderate-to-severe rheumatoid arthritis for at least 6 months before screening, and inadequate response to current methotrexate treatment (oral or injected 15-25 mg once weekly, or ≥10 mg once weekly if reduced due to side-effects or intolerance). Participants were randomly assigned via an interactive web response system (1:1:1:1, block size of four, stratified by age) to oral CPL'116 (60 mg, 120 mg, or 240 mg) or placebo twice daily for 12 weeks, with continuation of background methotrexate. The primary endpoint of the study was the change from baseline in Disease Activity Score based on 28 joints and C-reactive protein (DAS28-CRP) at week 12, analysed with a mixed-effects repeated measures model by a modified intention-to-treat approach. p values were nominal. Safety parameters including adverse events, vital functions, and laboratory results were closely monitored and reported for the safety analysis population, comprising all participants who received at least one dose of CPL'116 or placebo. People with lived experience were not involved in the study. The trial was registered with ClinicalTrials.gov, NCT05374785, and is completed.</p><p><strong>Findings: </strong>Between May 30, 2022, and Feb 7, 2024, 106 patients were randomly assigned (27 in the CPL'116 60 mg group, 25 in the 120 mg group, 26 in the 240 mg group, and 28 in the placebo group). Overall mean age was 54·4 years (SD 10·5); 79 (75%) of 106 participants were women and 27 (25%) were men, and all individuals self-reported as White. The least squares mean difference in the change from baseline in DAS28-CRP at 12 weeks with CPL'116 versus placebo was -0·15 (95% CI -0·81 to 0·52; p=0·67) for the 60 mg dose; -0·56 (-1·25 to 0·12; p=0·10) for the 120 mg dose; and -0·89 (-1·56 to -0·22; p=0·010) for the 240 mg dose","PeriodicalId":48540,"journal":{"name":"Lancet Rheumatology","volume":" ","pages":""},"PeriodicalIF":15.0,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144295149","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":"Exposure to hydroxychloroquine in early pregnancy and incidence of pre-eclampsia and pre-term delivery in patients with systemic lupus erythematosus in Sweden: a nationwide population-based cohort study.","authors":"Ngoc V Nguyen, Anna Sandström, Elisabet Svenungsson, Annica Dominicus, Elizabeth V Arkema, Julia F Simard","doi":"10.1016/S2665-9913(25)00076-1","DOIUrl":"https://doi.org/10.1016/S2665-9913(25)00076-1","url":null,"abstract":"<p><strong>Background: </strong>Pregnant women with systemic lupus erythematosus (SLE) have elevated risks of pre-eclampsia and pre-term delivery. Hydroxychloroquine, the mainstay treatment during pregnancy in women with SLE, is currently a promising agent for pre-eclampsia prevention. We aimed to examine associations between hydroxychloroquine use and pre-eclampsia and pre-term delivery in pregnant women with SLE.</p><p><strong>Methods: </strong>In this nationwide population-based cohort study, we included all singleton pregnancies of women with prevalent SLE that lead to a delivery (livebirths and stillbirths) between Jan 1, 2007, and Dec 31, 2022, diagnosed in secondary or tertiary care centres in Sweden. Hydroxychloroquine exposure was defined as two or more dispensations from 3 months pre-pregnancy until the end of the first trimester. The primary outcomes were pre-eclampsia (diagnosed from 20<sup>+0</sup> weeks of gestation to 6 weeks postpartum) and pre-term delivery (delivery before 37<sup>+0</sup> weeks of gestation). Inverse probability of treatment weighting adjusted for measured confounders (eg, maternal smoking, BMI, reproductive characteristics, pre-gestational hypertension, glucocorticoid use) and modified Poisson models estimated risk ratios and 95% confidence intervals. We involved a person with lived experience of pregnancy with SLE in all aspects of the study.</p><p><strong>Findings: </strong>Between Jan 1, 2007, and Dec 31, 2022, we included 959 singleton pregnancies from 685 women with prevalent SLE in Sweden. 404 (42%) of 959 pregnancies were nulliparous pregnancies (232 [57%] were unexposed and 172 [43%] were hydroxychloroquine-exposed) and 555 (58%) were parous pregnancies (333 [60%] were unexposed and 222 [40%] were hydroxychloroquine-exposed). The mean maternal age was 32 years (SD 4·7). Pre-eclampsia was recorded in 19 (11%) of 172 hydroxychloroquine-exposed pregnancies and 30 (13%) of 232 unexposed pregnancies in the nulliparous group and 12 (5%) of 222 hydroxychloroquine-exposed pregnancies and 20 (6%) of 333 unexposed pregnancies in the parous group. Pre-term delivery was recorded in 33 (19%) of 172 hydroxychloroquine-exposed pregnancies and 34 (15%) of 232 in unexposed pregnancies in the nulliparous group and 26 (12%) of 222 hydroxychloroquine-exposed pregnancies and 41 (12%) of 333 unexposed pregnancies in the parous group. The adjusted risk ratio for pre-eclampsia in SLE pregnancies with hydroxychloroquine exposure versus those without exposure was 0·49 (95% CI 0·31-0·79) overall, 0·59 (0·33-1·08) in the nulliparous group, and 0·44 (0·22-0·89) in the parous group. Associations between hydroxychloroquine and pre-term delivery were unclear in the overall (risk ratio 0·95 [95% CI 0·67-1·34]), nulliparous (1·10 [0·68-1·80]), and parous (0·75 [0·47-1·24]) groups. Stratification by antiphospholipid syndrome, renal diseases, and hypertension showed similar results.</p><p><strong>Interpretation: </strong>In this large coh","PeriodicalId":48540,"journal":{"name":"Lancet Rheumatology","volume":" ","pages":""},"PeriodicalIF":15.0,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144295150","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}