Lancet Rheumatology最新文献

{"title":"Effectiveness and persistence of biological and targeted synthetic treatment in patients with rheumatoid arthritis and chronic kidney disease: a multicentre, prospective cohort study","authors":"Sho Fukui MD, Hilde S Ørbo MD, Sara K Tedeschi MD, Zeynep S Tuzun MD, Hongshu Guan PhD, Leslie R Harrold MD, Heather J Litman PhD, Tomohiro Shinozaki PhD, Prof Mitsumasa Kishimoto PhD, Prof Yoshinori Komagata PhD, Prof Takeaki Matsuda PhD, Prof Wolfgang C Winkelmayer ScD, Prof Daniel H Solomon MD","doi":"10.1016/S2665-9913(26)00046-9","DOIUrl":"10.1016/S2665-9913(26)00046-9","url":null,"abstract":"<div><h3>Background</h3><div>Chronic kidney disease is a common comorbidity of rheumatoid arthritis. Because there has been scarce and conflicting evidence on the use of biological and targeted synthetic therapy in patients with rheumatoid arthritis and chronic kidney disease, we aimed to examine the effectiveness and persistence of biological and targeted synthetic disease-modifying antirheumatic drugs (DMARDs) for patients with rheumatoid arthritis and chronic kidney disease.</div></div><div><h3>Methods</h3><div>This multicentre, prospective cohort study used data from the CorEvitas Rheumatoid Arthritis registry on patients with rheumatoid arthritis who initiated each type of biological and targeted synthetic DMARD (TNF inhibitors, CTLA4 immunoglobulin, IL-6 inhibitors, B-cell depletion therapy, and JAK inhibitors) recruited from 160 rheumatology practices in the USA. Patients were required to have moderate or high disease activity according to the Clinical Disease Activity Index (CDAI; score >10). Chronic kidney disease was defined as an estimated glomerular filtration rate (eGFR) of less than 60 mL/min per 1·73 m<sup>2</sup> at biological or targeted synthetic DMARD initiation. The primary outcome was the attainment of remission according to CDAI score. Propensity scores were used for overlap weighting to improve the balance of characteristics for patients with and without reduced eGFR. Cox regressions estimated the unadjusted and adjusted hazard ratio (HR) of reduced eGFR for CDAI-based remission. People with lived experience of rheumatoid arthritis were not involved in the study design or conduct.</div></div><div><h3>Findings</h3><div>Between Oct 1, 2001, and Dec 31, 2023, 12 123 biological and targeted synthetic DMARD treatment initiations in 9601 patients with rheumatoid arthritis, with 51 931 person-years of follow-up, were identified. Of 12 123 eligible biological and targeted synthetic DMARD treatment initiations, 10 857 (89·6%) were in patients with preserved eGFR and 1266 (10·4%) were in patients with reduced eGFR. Across both groups, median age was 59·0 years (IQR 50·0–67·0), 9720 (80·2%) of 12 123 treatment initiations were in female patients and 2403 (19·8%) were in male patients, and 9908 (81·7%) were in non-Hispanic White patients. 3025 (27·9%) of 10 857 treatment initiations in patients with preserved eGFR resulted in CDAI-based remission versus 246 (19·4%) of 1266 treatment initiations in patients with reduced eGFR. Reduced eGFR was associated with a lower likelihood of attaining CDAI-based remission (unadjusted HR 0·71 [95% CI 0·62–0·82], adjusted HR 0·76 [0·66–0·88]) compared with preserved eGFR.</div></div><div><h3>Interpretation</h3><div>Although biological and targeted synthetic DMARDs are generally well tolerated and effective options, patients with rheumatoid arthritis and reduced eGFR have lower likelihood of attaining remission. Tailored treatment strategies for this high-risk population should be established.</div","PeriodicalId":48540,"journal":{"name":"Lancet Rheumatology","volume":"8 7","pages":"Pages e550-e562"},"PeriodicalIF":29.5,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147786014","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":"Correction to Lancet Rheumatol 2026; 8: e265–73","authors":"","doi":"10.1016/S2665-9913(26)00181-5","DOIUrl":"10.1016/S2665-9913(26)00181-5","url":null,"abstract":"","PeriodicalId":48540,"journal":{"name":"Lancet Rheumatology","volume":"8 7","pages":"Page e509"},"PeriodicalIF":29.5,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148043915","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":"Baricitinib and ruxolitinib use through the UK HLH Network","authors":"Amelia Holloway, Dreen Gul, Alexandra E Oppong, Hisham Alawad, Elizabeth Rankin, Matthew Steel, Jamie Macleod, David Donaldson, Iman Qureshi, Caitlin Benham, Xin Hui Chan, Raquel Faria, Reece Smith, Daniel Pietsch, Mary Owen, Alexis Jones, Ben Carpenter, Arian Laurence, Rachel S Tattersall, Jessica J Manson, Satyen H Gohil","doi":"10.1016/S2665-9913(26)00119-0","DOIUrl":"10.1016/S2665-9913(26)00119-0","url":null,"abstract":"","PeriodicalId":48540,"journal":{"name":"Lancet Rheumatology","volume":"8 7","pages":"Pages e500-e504"},"PeriodicalIF":29.5,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148043195","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":"Announcing The Lancet Rheumatology commission on reproductive health and family planning in immune-mediated long-term conditions: empowering special reproductive journeys","authors":"Karen Schreiber, Anna Clark, Laura Andreoli","doi":"10.1016/S2665-9913(26)00157-8","DOIUrl":"10.1016/S2665-9913(26)00157-8","url":null,"abstract":"","PeriodicalId":48540,"journal":{"name":"Lancet Rheumatology","volume":"8 7","pages":"Pages e497-e500"},"PeriodicalIF":29.5,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148151269","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":"Beyond laboratory tests: when normal results aren’t the finish line","authors":"Dana Guglielmo MPH","doi":"10.1016/S2665-9913(26)00178-5","DOIUrl":"10.1016/S2665-9913(26)00178-5","url":null,"abstract":"","PeriodicalId":48540,"journal":{"name":"Lancet Rheumatology","volume":"8 7","pages":"Pages e511-e512"},"PeriodicalIF":29.5,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147983912","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":"Silent patients, silent disease: misalignment in patient-initiated follow-up – Authors reply","authors":"Alice E Jennings, Ailsa Bosworth, Mel Brooke, James Galloway, Mark G Perry, Helen Lall, Rob Law, Laura C Coates, Emma Dures","doi":"10.1016/S2665-9913(26)00150-5","DOIUrl":"10.1016/S2665-9913(26)00150-5","url":null,"abstract":"","PeriodicalId":48540,"journal":{"name":"Lancet Rheumatology","volume":"8 7","pages":"Pages e507-e508"},"PeriodicalIF":29.5,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148206572","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(26)00186-4","DOIUrl":"10.1016/S2665-9913(26)00186-4","url":null,"abstract":"","PeriodicalId":48540,"journal":{"name":"Lancet Rheumatology","volume":"8 7","pages":"Page e510"},"PeriodicalIF":29.5,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148529218","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":"Aligning approaches to rheumatoid arthritis drug development: a comparison of FDA and EMA guidance","authors":"Antonio Ciancio MD,&nbsp;Andrea Amati MD,&nbsp;Saviana Gandolfo MD,&nbsp;Prof Ricardo Grieshaber-Bouyer MD PhD,&nbsp;Prof Ranjeny Thomas MD,&nbsp;David F L Liew MD,&nbsp;Guillermo Valenzuela MD,&nbsp;Prof Laure Gossec MD PhD,&nbsp;Maria Manara MD,&nbsp;Prof Tae-Hwan Kim MD PhD,&nbsp;Prof Zoltán Szekanecz MD PhD,&nbsp;Prof Peter C Taylor MD PhD,&nbsp;Prof Xavier Mariette MD PhD,&nbsp;Prof Roberto Caporali MD PhD,&nbsp;Prof Francesco Ciccia MD PhD","doi":"10.1016/S2665-9913(26)00086-X","DOIUrl":"10.1016/S2665-9913(26)00086-X","url":null,"abstract":"<div><div>This Health Policy compares the current recommendations from the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for new treatments in rheumatoid arthritis, highlighting where they align, where they differ, and how harmonisation could make drug development more efficient. We examined the EMA's Guidelines on Clinical Trials of Medicinal Products for the Treatment of rheumatoid arthritis and the FDA's draft guidance rheumatoid arthritis Development of Drugs for Treatment, together with relevant cross-indication FDA guidelines and labelling decisions in rheumatoid arthritis in the last two decades. The key aspects of trial design, including study populations, endpoints, safety requirements, and statistical considerations were analysed. The findings were reviewed and interpreted by a panel of rheumatologists, who proposed strategies for aligning regulatory expectations. The FDA and EMA agree on several core principles such as the use of composite clinical endpoints, validated patient-reported outcomes, the importance of preventing structural joint damage, need for adequate long-term safety exposure, and limits on placebo duration. The EMA, however, favours remission or low disease activity as the preferred primary endpoints, generally requires two pivotal trials in distinct rheumatoid arthritis populations, and background methotrexate unless contraindicated. The FDA offers more flexibility in primary endpoint selection, allows for a single pivotal trial if supported by strong confirmatory evidence, and places greater emphasis on early dose-response characterisation. Greater alignment between FDA and EMA requirements could help reduce duplication, streamline global data interpretation, and speed patient access to effective rheumatoid arthritis therapies globally.</div></div>","PeriodicalId":48540,"journal":{"name":"Lancet Rheumatology","volume":"8 7","pages":"Pages e563-e575"},"PeriodicalIF":29.5,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148303612","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":"Efficacy and safety of branebrutinib (BMS-986195), an irreversible Bruton's tyrosine kinase inhibitor, for the treatment of rheumatoid arthritis: a phase 2a, randomised, double-blind, placebo-controlled study","authors":"Prof Mikkel Østergaard DMSc,&nbsp;Prof Espen A Haavardsholm MD,&nbsp;Miroslawa Nowak MD PhD,&nbsp;Yi Luo PhD,&nbsp;Jessica Landis PhD,&nbsp;Aberra Fura PhD,&nbsp;Chahin Pachai PhD,&nbsp;Duncan Rotich PhD,&nbsp;Yanlin Wang-Fischer MD PhD,&nbsp;Leonidas N Carayannopoulos MD,&nbsp;David Zammit PhD,&nbsp;Hazem Karabeber MD,&nbsp;Alice Wang MD,&nbsp;Dennis M Grasela PharmD PhD","doi":"10.1016/S2665-9913(25)00374-1","DOIUrl":"10.1016/S2665-9913(25)00374-1","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;Branebrutinib, an oral, highly selective, and irreversible Bruton's tyrosine kinase inhibitor, is a potential candidate for rheumatoid arthritis treatment as Bruton's tyrosine kinase has a role in B-cell activation, autoantibody production, and proinflammatory cytokine release, all of which are implicated in rheumatoid arthritis disease activity and progression. This study assessed the efficacy and safety of branebrutinib in patients with rheumatoid arthritis and an inadequate response to methotrexate.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;This phase 2a, randomised, double-blind, placebo-controlled study was designed to assess the efficacy and safety of branebrutinib in patients with rheumatoid arthritis, systemic lupus erythematosus, or primary Sjögren's disease. Here, we report the results of the rheumatoid arthritis substudy, done in the USA, Poland, and Spain across 24 sites. The study included a 12-week double-blind treatment period followed by an additional 12-week open-label period with abatacept treatment. Only data for the double-blind treatment period are reported here. Eligible patients were aged 18–75 years, met the 2010 American College of Rheumatology (ACR)–European Alliance of Associations for Rheumatology criteria for rheumatoid arthritis, had disease duration less than 4 years, and had inadequate response to methotrexate. Patients were randomly assigned (3:1) to receive branebrutinib 9 mg once daily or placebo for 12 weeks. Randomisation was carried out centrally according to a computer-generated block randomisation scheme using interactive response technology. All parties were masked to treatment allocation. The primary endpoint was the proportion of patients who had 50% improvement in the ACR response criteria (ACR50) at week 12, assessed in all participants randomly assigned to treatment (full analysis set). Safety was assessed in patients who received at least one dose of branebrutinib or placebo. This trial was 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;NCT04186871&lt;/span&gt;&lt;svg&gt;&lt;path&gt;&lt;/path&gt;&lt;/svg&gt;&lt;/span&gt;. Patients with lived experience of rheumatoid arthritis were not involved in the study design.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Findings&lt;/h3&gt;&lt;div&gt;Between Jan 7, 2020, to Dec 5, 2022, 85 patients were randomly assigned to receive branebrutinib (n=64) or placebo (n=21). 63 (74%) of 85 patients were female, 22 (26%) were male, 80 (94%) were White, and the mean age was 49·1 years (SD 12·0). The primary endpoint of ACR50 response at week 12 was not met; 12 (19%) of 64 patients had an ACR50 response in the branebrutinib group compared with seven (33%) of 21 patients in the placebo group (p=0·16). Adverse events were similar between the two groups (30 [47%] of 64 in the branebrutinib group and 8 [38%] of 21 in the placebo group), with no reported serious adverse events or deaths.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Interpretation&lt;/h3&gt;&lt;div&gt;There was no significant difference betwee","PeriodicalId":48540,"journal":{"name":"Lancet Rheumatology","volume":"8 7","pages":"Pages e539-e549"},"PeriodicalIF":29.5,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147844839","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":"Efficacy and safety of enpatoran, a Toll-like receptor 7/8 inhibitor, in patients with skin manifestations of cutaneous lupus erythematosus or systemic lupus erythematosus: findings from Cohort A of a multicentre, international, double-blind, placebo-controlled, dose-finding phase 2 trial","authors":"Prof Eric F Morand PhD,&nbsp;Prof Victoria P Werth MD,&nbsp;Prof Joerg Wenzel MD,&nbsp;Prof Richard Furie MD,&nbsp;Prof Maria Dall’Era MD,&nbsp;Prof Jorge Sanchez-Guerrero MD,&nbsp;Sanjeev Roy MD,&nbsp;Summer G Goodson PhD,&nbsp;Flavie Moreau MSc,&nbsp;Hans Gühring MD,&nbsp;Evridiki Sgouroudi PhD,&nbsp;Lena Klopp-Schulze PhD,&nbsp;David R Pearson MD","doi":"10.1016/S2665-9913(25)00337-6","DOIUrl":"10.1016/S2665-9913(25)00337-6","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;Toll-like receptor (TLR)7 and TLR8 are nucleic-acid sensors involved in lupus pathogenesis. We aimed to investigate the efficacy and safety of enpatoran, an oral small-molecule TLR7/8 inhibitor, in participants with active skin manifestations of cutaneous lupus erythematosus (CLE) or systemic lupus erythematosus (SLE).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;WILLOW is a phase 2, randomised, double-blind, placebo-controlled, basket, dose-finding study conducted across 132 centres in 22 countries, enrolling patients into two cohorts (A and B) with different eligibility criteria. In Cohort A of the trial, we enrolled participants aged 18–75 years who had CLE only or SLE with mild or no extra-mucocutaneous disease activity (British Isles Lupus Assessment Group [BILAG]-2004 scores 1B, C, or D), and a Cutaneous Lupus Disease Area and Severity Index–activity (CLASI-A) score of 8 or higher. Participants were randomised (1:1:1:1) to receive placebo or enpatoran at a dose of 25 mg, 50 mg, or 100 mg twice per day for 24 weeks, in combination with standard of care. The primary objective was to evaluate the dose–response relationship of enpatoran in reducing disease activity, based on the percentage change from baseline in CLASI-A total score at week 16, analysed with a multiple comparison procedure–modelling approach. Efficacy analyses were done in the full analysis set of all randomly allocated participants. Safety was assessed in all patients who received at least one dose of study treatment. There was no involvement of people with lived experience of CLE or SLE in study design. This trial 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;NCT05162586&lt;/span&gt;&lt;svg&gt;&lt;path&gt;&lt;/path&gt;&lt;/svg&gt;&lt;/span&gt;; completed); results from Cohort B will be reported separately.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Findings&lt;/h3&gt;&lt;div&gt;Between May 4, 2022, and Feb 6, 2024, 463 patients were screened for eligibility across cohorts A and B; 102 participants were randomly assigned within Cohort A and received treatment (safety population). Two participants (n=1 each from the enpatoran 25 mg and 50 mg groups) were randomly allocated to Cohort A but were subsequently found to have had BILAG scores ≥1A and 2B at screening and were therefore deemed ineligible and excluded; thus 100 participants were analysed for efficacy (placebo group n=26; enpatoran 25 mg group n=23; enpatoran 50 mg group n=25; enpatoran 100 mg group n=26). Participants in the full analysis set had a median age of 47 years (IQR 36–55); 77 (77%) were female, 23 (23%) were male, and 48 (48%) were White. At week 16, enpatoran had a significant, dose-dependent effect on CLASI-A score, with adjusted mean changes from baseline of –64 percentage points (95% CI –70 to –58) in the enpatoran 25 mg group, –68 percentage points (–75 to –61) in the enpatoran 50 mg group, and –72 percentage points (–80 to –64) in the enpatoran 100 mg group, versus –44 percentage points (–55 to –33","PeriodicalId":48540,"journal":{"name":"Lancet Rheumatology","volume":"8 7","pages":"Pages e513-e527"},"PeriodicalIF":29.5,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147870109","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}