Pub Date : 2024-09-17DOI: 10.1016/S2665-9913(24)00226-1
Serena Bugatti, Georg Schett
{"title":"Prevention of seronegative rheumatoid arthritis: an entity of its own.","authors":"Serena Bugatti, Georg Schett","doi":"10.1016/S2665-9913(24)00226-1","DOIUrl":"https://doi.org/10.1016/S2665-9913(24)00226-1","url":null,"abstract":"","PeriodicalId":48540,"journal":{"name":"Lancet Rheumatology","volume":null,"pages":null},"PeriodicalIF":15.0,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142298935","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}
Pub Date : 2024-09-10DOI: 10.1016/S2665-9913(24)00249-2
Begonya Alcacer-Pitarch , Francesco Del Galdo , Helena Marzo-Ortega
{"title":"Clinical hypnosis and pain management in sharp debridement of skin ulcers in immune-mediated inflammatory diseases","authors":"Begonya Alcacer-Pitarch , Francesco Del Galdo , Helena Marzo-Ortega","doi":"10.1016/S2665-9913(24)00249-2","DOIUrl":"10.1016/S2665-9913(24)00249-2","url":null,"abstract":"","PeriodicalId":48540,"journal":{"name":"Lancet Rheumatology","volume":null,"pages":null},"PeriodicalIF":15.0,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142262180","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}
Pub Date : 2024-09-02DOI: 10.1016/S2665-9913(24)00194-2
Zhenyu Zhong MD , Prof Dan Deng PhD , Yu Gao MD , Qingqing Bu MAS , Lingyu Dai MD , Xiaojie Feng MD , Chong Tang MD , Xiang Luo BS , Yao Wang BS , Chunjiang Zhou MPA , Guannan Su PhD , Prof Peizeng Yang MD
<div><h3>Background</h3><div>Data from head-to-head trials of immunomodulatory therapies for Behçet's disease are scarce. We aimed to compare the efficacy and safety of ciclosporin, interferon alfa-2a, and adalimumab, each combined with corticosteroids, in preventing uveitis relapse in patients with severe Behçet's disease.</div></div><div><h3>Methods</h3><div>We did a randomised, open-label, assessor-masked, head-to-head trial at a large, specialised uveitis centre in Chongqing, China. Patients aged 18 years or older with severe Behçet's disease uveitis on corticosteroids and naive to anti-TNF therapy were eligible. Patients were randomly assigned in a 1:1:1 ratio to ciclosporin (2–5 mg/kg per day orally), interferon alfa-2a (3 million IU per day subcutaneously), or adalimumab (40 mg every 2 weeks subcutaneously), each combined with a tapering dose of corticosteroids with subsequent dose adjustments. The primary outcome was the annualised relapse rate of uveitis, assessed in the full analysis set (all randomly assigned patients with at least one post-baseline assessment). The non-inferiority margin of difference between the interferon alfa-2a and adalimumab groups was set to 1·0 for the primary outcome. Safety was assessed in all patients who received at least one dose of trial drugs. Individuals with lived experience of Behçet's disease uveitis were involved in the trial design and implementation. This study is registered with Chinese Clinical Trial Registry, ChiCTR2000031637. The trial is ongoing, but is closed to new participants.</div></div><div><h3>Findings</h3><div>Between May 12, 2020, and Feb 22, 2022, a total of 270 patients (mean age 38·1 years [SD 9·8]; 213 [79%] men, 57 [21%] women; 270 [100%] east Asian ethnicity) were randomly assigned to ciclosporin, interferon alfa-2a, or adalimumab (n=90 in each group); 261 patients were included in the full analysis set. For the primary outcome, the least-squares mean was 1·84 (95% CI 1·40 to 2·44) with ciclosporin, 1·44 (1·10 to 1·89) with interferon alfa-2a, and 0·95 (0·64 to 1·40) with adalimumab. The annualised relapse rate was significantly higher in patients receiving ciclosporin than in those receiving adalimumab (least-squares mean difference 0·90 [95% CI 0·27 to 1·53]; p=0·0054 for superiority). The least-squares mean difference between interferon alfa-2a and adalimumab was 0·50 (–0·04 to 1·04), which did not meet non-inferiority criteria (p=0·034 for non-inferiority). The primary outcome did not differ substantially between interferon alfa-2a and ciclosporin (least-squares mean difference –0·40 [–1·05 to 0·25]; p=0·23 for superiority). Serious adverse events were reported in 12 (13%) of 90 patients on ciclosporin plus corticosteroids, eight (9%) of 90 patients on interferon alfa-2a plus corticosteroids, and seven (8%) of 90 patients on adalimumab plus corticosteroids. There were no treatment-related deaths.</div></div><div><h3>Interpretation</h3><div>Adalimumab plus corticosteroids wa
{"title":"Combinations of immunomodulatory agents for prevention of uveitis relapse in patients with severe Behçet's disease already on corticosteroid therapy: a randomised, open-label, head-to-head trial","authors":"Zhenyu Zhong MD , Prof Dan Deng PhD , Yu Gao MD , Qingqing Bu MAS , Lingyu Dai MD , Xiaojie Feng MD , Chong Tang MD , Xiang Luo BS , Yao Wang BS , Chunjiang Zhou MPA , Guannan Su PhD , Prof Peizeng Yang MD","doi":"10.1016/S2665-9913(24)00194-2","DOIUrl":"10.1016/S2665-9913(24)00194-2","url":null,"abstract":"<div><h3>Background</h3><div>Data from head-to-head trials of immunomodulatory therapies for Behçet's disease are scarce. We aimed to compare the efficacy and safety of ciclosporin, interferon alfa-2a, and adalimumab, each combined with corticosteroids, in preventing uveitis relapse in patients with severe Behçet's disease.</div></div><div><h3>Methods</h3><div>We did a randomised, open-label, assessor-masked, head-to-head trial at a large, specialised uveitis centre in Chongqing, China. Patients aged 18 years or older with severe Behçet's disease uveitis on corticosteroids and naive to anti-TNF therapy were eligible. Patients were randomly assigned in a 1:1:1 ratio to ciclosporin (2–5 mg/kg per day orally), interferon alfa-2a (3 million IU per day subcutaneously), or adalimumab (40 mg every 2 weeks subcutaneously), each combined with a tapering dose of corticosteroids with subsequent dose adjustments. The primary outcome was the annualised relapse rate of uveitis, assessed in the full analysis set (all randomly assigned patients with at least one post-baseline assessment). The non-inferiority margin of difference between the interferon alfa-2a and adalimumab groups was set to 1·0 for the primary outcome. Safety was assessed in all patients who received at least one dose of trial drugs. Individuals with lived experience of Behçet's disease uveitis were involved in the trial design and implementation. This study is registered with Chinese Clinical Trial Registry, ChiCTR2000031637. The trial is ongoing, but is closed to new participants.</div></div><div><h3>Findings</h3><div>Between May 12, 2020, and Feb 22, 2022, a total of 270 patients (mean age 38·1 years [SD 9·8]; 213 [79%] men, 57 [21%] women; 270 [100%] east Asian ethnicity) were randomly assigned to ciclosporin, interferon alfa-2a, or adalimumab (n=90 in each group); 261 patients were included in the full analysis set. For the primary outcome, the least-squares mean was 1·84 (95% CI 1·40 to 2·44) with ciclosporin, 1·44 (1·10 to 1·89) with interferon alfa-2a, and 0·95 (0·64 to 1·40) with adalimumab. The annualised relapse rate was significantly higher in patients receiving ciclosporin than in those receiving adalimumab (least-squares mean difference 0·90 [95% CI 0·27 to 1·53]; p=0·0054 for superiority). The least-squares mean difference between interferon alfa-2a and adalimumab was 0·50 (–0·04 to 1·04), which did not meet non-inferiority criteria (p=0·034 for non-inferiority). The primary outcome did not differ substantially between interferon alfa-2a and ciclosporin (least-squares mean difference –0·40 [–1·05 to 0·25]; p=0·23 for superiority). Serious adverse events were reported in 12 (13%) of 90 patients on ciclosporin plus corticosteroids, eight (9%) of 90 patients on interferon alfa-2a plus corticosteroids, and seven (8%) of 90 patients on adalimumab plus corticosteroids. There were no treatment-related deaths.</div></div><div><h3>Interpretation</h3><div>Adalimumab plus corticosteroids wa","PeriodicalId":48540,"journal":{"name":"Lancet Rheumatology","volume":null,"pages":null},"PeriodicalIF":15.0,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142141389","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}
Pub Date : 2024-09-02DOI: 10.1016/S2665-9913(24)00222-4
Jian-long Guan , Jun Zou
{"title":"Uveitis relapse in Behçet's disease: a more nuanced approach is needed","authors":"Jian-long Guan , Jun Zou","doi":"10.1016/S2665-9913(24)00222-4","DOIUrl":"10.1016/S2665-9913(24)00222-4","url":null,"abstract":"","PeriodicalId":48540,"journal":{"name":"Lancet Rheumatology","volume":null,"pages":null},"PeriodicalIF":15.0,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142141390","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}
Pub Date : 2024-08-28DOI: 10.1016/S2665-9913(24)00189-9
Gabrielle Virgili-Gervais MSc , Bianca Matthews BSc , Elsa-Lynn Nassar MSc , Marie-Eve Carrier MSc , Linda Kwakkenbos PhD , John D Pauling MD , Prof Susan J Bartlett PhD , Amy Gietzen , Karen Gottesman BA , Geneviève Guillot PDt , Marie Hudson MD , Laura K Hummers MD , Amanda Lawrie-Jones , Prof Vanessa L Malcarne PhD , Prof Maureen D Mayes MD , Michelle Richard DSW , Maureen Sauvé BA , Robyn K Wojeck PhD , Prof Luc Mouthon MD , Andrea Benedetti PhD , Sabrina Provencher
Background
Raynaud's phenomenon is the earliest and most common systemic sclerosis manifestation. Episodes can be triggered by cold exposure and ambient temperature changes. Small studies have found that Raynaud's phenomenon outcomes were associated with season. We aimed to map the degree that differences in ambient temperature are associated with Raynaud's phenomenon outcomes across the temperature spectrum.
Methods
People with Raynaud's phenomenon secondary to systemic sclerosis in the Scleroderma Patient-centered Intervention Network Cohort completed past-week Raynaud's phenomenon severity assessments (0–10 numerical rating scale) at enrolment and longitudinally at 3-month intervals. Mean daily temperature and feels like temperature, which incorporates wind chill and humidity, for the week before each assessment were extracted for each participant from a weather site close to the participant's recruiting centre via the Iowa Environmental Mesonet. We used linear mixed models with basis splines to flexibly model non-linear changes in Raynaud's phenomenon severity across the temperature spectrum. People with lived experience of systemic sclerosis contributed to the study design and interpretation.
Findings
Between April 15, 2014 and Aug 1, 2023, we included data on 20 233 Raynaud's phenomenon severity assessments from 2243 participants. 1964 (88%) of 2243 participants were women, 279 (12%) were men, and 1813 (82%) were White. Mean age was 54·8 (SD 12·7) years. The maximum predicted Raynaud's phenomenon severity score was 6·8 points (95% CI 5·6–8·1), which occurred at –25°C. Severity scores decreased minimally from –15°C to 5°C (0·05–0·21 points per 5°C difference), then decreased in larger steps between 5°C and 25°C (0·37–0·54 points per 5°C difference). The minimum predicted score was at 25°C (2·6 points [95% CI 2·5–2·7]). Scores increased at temperatures above 25°C to 3·5 points (3·0–4·1) at 35°C and 5·6 points (4·5–6·8) at 40°C. Results were similar for feels like temperature.
Interpretation
Raynaud's phenomenon severity is worst at very cold temperatures but also increases with very warm temperatures, presumably due to air conditioning. Clinical management and Raynaud's phenomenon intervention trial designs should consider temperature patterns.
Funding
Scleroderma Society of Ontario, Scleroderma Canada, Sclérodermie Québec, Scleroderma Manitoba, Scleroderma Atlantic, Scleroderma Association of BC, Scleroderma SASK, Scleroderma Australia, Scleroderma New South Wales, Scleroderma Victoria, the Canadian Institutes of Health Research, the Arthritis Society, the Lady Davis Institute for Medical Research of the Jewish General Hospital, the Jewish General Hospital Foundation, and McGill University.
{"title":"The association of outdoor temperature and self-reported Raynaud's phenomenon severity among people with systemic sclerosis: a Scleroderma Patient-centered Intervention Network Cohort study","authors":"Gabrielle Virgili-Gervais MSc , Bianca Matthews BSc , Elsa-Lynn Nassar MSc , Marie-Eve Carrier MSc , Linda Kwakkenbos PhD , John D Pauling MD , Prof Susan J Bartlett PhD , Amy Gietzen , Karen Gottesman BA , Geneviève Guillot PDt , Marie Hudson MD , Laura K Hummers MD , Amanda Lawrie-Jones , Prof Vanessa L Malcarne PhD , Prof Maureen D Mayes MD , Michelle Richard DSW , Maureen Sauvé BA , Robyn K Wojeck PhD , Prof Luc Mouthon MD , Andrea Benedetti PhD , Sabrina Provencher","doi":"10.1016/S2665-9913(24)00189-9","DOIUrl":"10.1016/S2665-9913(24)00189-9","url":null,"abstract":"<div><h3>Background</h3><div>Raynaud's phenomenon is the earliest and most common systemic sclerosis manifestation. Episodes can be triggered by cold exposure and ambient temperature changes. Small studies have found that Raynaud's phenomenon outcomes were associated with season. We aimed to map the degree that differences in ambient temperature are associated with Raynaud's phenomenon outcomes across the temperature spectrum.</div></div><div><h3>Methods</h3><div>People with Raynaud's phenomenon secondary to systemic sclerosis in the Scleroderma Patient-centered Intervention Network Cohort completed past-week Raynaud's phenomenon severity assessments (0–10 numerical rating scale) at enrolment and longitudinally at 3-month intervals. Mean daily temperature and feels like temperature, which incorporates wind chill and humidity, for the week before each assessment were extracted for each participant from a weather site close to the participant's recruiting centre via the Iowa Environmental Mesonet. We used linear mixed models with basis splines to flexibly model non-linear changes in Raynaud's phenomenon severity across the temperature spectrum. People with lived experience of systemic sclerosis contributed to the study design and interpretation.</div></div><div><h3>Findings</h3><div>Between April 15, 2014 and Aug 1, 2023, we included data on 20 233 Raynaud's phenomenon severity assessments from 2243 participants. 1964 (88%) of 2243 participants were women, 279 (12%) were men, and 1813 (82%) were White. Mean age was 54·8 (SD 12·7) years. The maximum predicted Raynaud's phenomenon severity score was 6·8 points (95% CI 5·6–8·1), which occurred at –25°C. Severity scores decreased minimally from –15°C to 5°C (0·05–0·21 points per 5°C difference), then decreased in larger steps between 5°C and 25°C (0·37–0·54 points per 5°C difference). The minimum predicted score was at 25°C (2·6 points [95% CI 2·5–2·7]). Scores increased at temperatures above 25°C to 3·5 points (3·0–4·1) at 35°C and 5·6 points (4·5–6·8) at 40°C. Results were similar for feels like temperature.</div></div><div><h3>Interpretation</h3><div>Raynaud's phenomenon severity is worst at very cold temperatures but also increases with very warm temperatures, presumably due to air conditioning. Clinical management and Raynaud's phenomenon intervention trial designs should consider temperature patterns.</div></div><div><h3>Funding</h3><div>Scleroderma Society of Ontario, Scleroderma Canada, Sclérodermie Québec, Scleroderma Manitoba, Scleroderma Atlantic, Scleroderma Association of BC, Scleroderma SASK, Scleroderma Australia, Scleroderma New South Wales, Scleroderma Victoria, the Canadian Institutes of Health Research, the Arthritis Society, the Lady Davis Institute for Medical Research of the Jewish General Hospital, the Jewish General Hospital Foundation, and McGill University.</div></div>","PeriodicalId":48540,"journal":{"name":"Lancet Rheumatology","volume":null,"pages":null},"PeriodicalIF":15.0,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142113579","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}
Pub Date : 2024-08-28DOI: 10.1016/S2665-9913(24)00243-1
Maurizio Cutolo , Vanessa Smith , Elvis Hysa
{"title":"Outdoor temperatures and Raynaud's phenomenon in patients with systemic sclerosis","authors":"Maurizio Cutolo , Vanessa Smith , Elvis Hysa","doi":"10.1016/S2665-9913(24)00243-1","DOIUrl":"10.1016/S2665-9913(24)00243-1","url":null,"abstract":"","PeriodicalId":48540,"journal":{"name":"Lancet Rheumatology","volume":null,"pages":null},"PeriodicalIF":15.0,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142113578","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}
Pub Date : 2024-08-26DOI: 10.1016/S2665-9913(24)00231-5
George Bertsias , Jinoos Yazdany
{"title":"Achievable but elusive: LLDAS and DORIS remission in clinical trials of belimumab","authors":"George Bertsias , Jinoos Yazdany","doi":"10.1016/S2665-9913(24)00231-5","DOIUrl":"10.1016/S2665-9913(24)00231-5","url":null,"abstract":"","PeriodicalId":48540,"journal":{"name":"Lancet Rheumatology","volume":null,"pages":null},"PeriodicalIF":15.0,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142113576","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}
Pub Date : 2024-08-26DOI: 10.1016/S2665-9913(24)00162-0
Ioannis Parodis MD , Julius Lindblom MD , Prof Roger A Levy MD , Margherita Zen MD , Nursen Cetrez MD , Alvaro Gomez MD , Shereen Oon MBBS , Christine Henning PharmD , Prof Munther Khamashta MD , Holly A Quasny PharmD , Deven Chauhan MSc , Prof Anca Askanase MD , Prof Ronald van Vollenhoven MD , Prof Mandana Nikpour MBBS
<div><h3>Background</h3><div>Disease remission or low disease activity are key treatment targets for patients with systemic lupus erythematosus (SLE). Pivotal trials of belimumab were conducted before the introduction of these targets. In this study, we aimed to pool data across trials to assess attainment of remission and low disease activity in a large, racially and culturally diverse patient population with SLE.</div></div><div><h3>Methods</h3><div>In this integrated post-hoc analysis, we pooled data from five phase 3 trials of belimumab (BLISS-76 [<span><span>NCT00410384</span><svg><path></path></svg></span>], BLISS-52 [<span><span>NCT00424476</span><svg><path></path></svg></span>], BLISS-NEA [<span><span>NCT01345253</span><svg><path></path></svg></span>], BLISS-SC [<span><span>NCT01484496</span><svg><path></path></svg></span>], and EMBRACE [<span><span>NCT01632241</span><svg><path></path></svg></span>]), in patients with active, autoantibody-positive SLE. Patients were randomly assigned to receive belimumab (10 mg/kg per month intravenously or 200 mg per week subcutaneously) or placebo, plus standard therapy. The proportion of patients with Definitions of Remission in SLE (DORIS) remission and lupus low disease activity state (LLDAS) were analysed every 4 weeks from week 4 to week 52 for belimumab versus placebo, using modified Poisson regression adjusted for trial variance, in all patients and in subgroups per baseline SLE Disease Activity Index-2000 score (<10 or ≥10); anti-double stranded DNA positivity (yes or no); low complement 3 (C3) or C4 levels (yes or no); anti-dsDNA positivity or low C3 or C4 levels (yes and no); prednisone-equivalent dose (≤7·5 mg per day or >7·5 mg per day); antimalarial use (yes or no); and by race (Black African ancestry or African American, Asian, Indigenous American, or White).</div></div><div><h3>Findings</h3><div>Data for 3086 patients (1869 in the belimumab group and 1217 in the placebo group) were analysed. 2913 (94%) of 3086 patients were women and 173 (6%) were men, and the median age was 36 years (IQR 28–45). The proportion of patients with DORIS remission was significantly higher in the belimumab group than the placebo group at weeks 28, 48, and 52 (week 52: 148 [8%] of 1869 participants <em>vs</em> 68 [6%] of 1217 participants; risk ratio 1·51 [95% CI 1·15–1·99]; p=0·0055). The proportion of patients who attained LLDAS was higher in the belimumab group than the placebo group at weeks 8, 24, 32–52 (week 52: 322 [17%] of 1869 participants <em>vs</em> 125 [10%] of 1217 participants; 1·74 [1·44–2·12]; p<0·0001). A higher proportion of patients had DORIS remission at week 52 in the belimumab group than the placebo group among all baseline subgroups denoting high disease activity, with the exception of those on a prednisone-equivalent dose higher than 7·5 mg per day in whom there was no difference for DORIS remission with belimumab versus placebo. The proportion of patients with LLDAS was signifi
背景：疾病缓解或疾病活动度低是系统性红斑狼疮（SLE）患者的主要治疗目标。贝利木单抗的关键性试验是在引入这些目标之前进行的。在这项研究中，我们旨在汇集各项试验的数据，以评估大量具有种族和文化多样性的系统性红斑狼疮患者达到缓解和低疾病活动度的情况：在这项综合事后分析中，我们汇总了贝利木单抗五项三期试验（BLISS-76 [NCT00410384]、BLISS-52 [NCT00424476]、BLISS-NEA [NCT01345253]、BLISS-SC [NCT01484496]和EMBRACE [NCT01632241]）的数据，这些试验均针对活动性自身抗体阳性系统性红斑狼疮患者。患者被随机分配接受贝利木单抗（每月静脉注射10毫克/千克或每周皮下注射200毫克）或安慰剂以及标准疗法。从第4周到第52周，每隔4周分析一次贝利木单抗与安慰剂的对比情况，采用经试验方差调整的改良泊松回归法，对所有患者以及按系统性红斑狼疮疾病活动指数-2000基线评分（每天7-5毫克）、抗疟药物使用情况（是或否）和种族（黑非洲血统或非裔美国人、亚洲人、土著美国人或白人）划分的亚组进行分析。研究结果：分析了3086名患者（贝利木单抗组1869人，安慰剂组1217人）的数据。3086名患者中有2913名（94%）为女性，173名（6%）为男性，年龄中位数为36岁（IQR为28-45岁）。在第28、48和52周，贝利木单抗组患者的DORIS缓解比例明显高于安慰剂组（第52周：1869名参与者中的148人[8%] vs 1217名参与者中的68人[6%]；风险比1-51 [95% CI 1-15-1-99]；P=0-0055）。在第8、24、32-52周，贝利木单抗组达到LLDAS的患者比例高于安慰剂组（第52周：1869名参与者中的322[17%]对1217名参与者中的125[10%]；1-74 [1-44-2-12]；p解释：在活动性系统性红斑狼疮成人患者中，贝利木单抗联合标准疗法比安慰剂联合标准疗法在获得DORIS缓解（两组均达到较低比例）和LLDAS方面的获益更大，最早在DORIS缓解的第28周和LLDAS的第8周就观察到了差异：瑞典风湿病协会、古斯塔夫五世国王 80 年基金会、瑞典医学会、Nyckelfonden、Nanna Svartz 教授基金会、Ulla 和 Roland Gustafsson 基金会、斯德哥尔摩地区以及卡罗林斯卡医学院。
{"title":"Attainment of remission and low disease activity after treatment with belimumab in patients with systemic lupus erythematosus: a post-hoc analysis of pooled data from five randomised clinical trials","authors":"Ioannis Parodis MD , Julius Lindblom MD , Prof Roger A Levy MD , Margherita Zen MD , Nursen Cetrez MD , Alvaro Gomez MD , Shereen Oon MBBS , Christine Henning PharmD , Prof Munther Khamashta MD , Holly A Quasny PharmD , Deven Chauhan MSc , Prof Anca Askanase MD , Prof Ronald van Vollenhoven MD , Prof Mandana Nikpour MBBS","doi":"10.1016/S2665-9913(24)00162-0","DOIUrl":"10.1016/S2665-9913(24)00162-0","url":null,"abstract":"<div><h3>Background</h3><div>Disease remission or low disease activity are key treatment targets for patients with systemic lupus erythematosus (SLE). Pivotal trials of belimumab were conducted before the introduction of these targets. In this study, we aimed to pool data across trials to assess attainment of remission and low disease activity in a large, racially and culturally diverse patient population with SLE.</div></div><div><h3>Methods</h3><div>In this integrated post-hoc analysis, we pooled data from five phase 3 trials of belimumab (BLISS-76 [<span><span>NCT00410384</span><svg><path></path></svg></span>], BLISS-52 [<span><span>NCT00424476</span><svg><path></path></svg></span>], BLISS-NEA [<span><span>NCT01345253</span><svg><path></path></svg></span>], BLISS-SC [<span><span>NCT01484496</span><svg><path></path></svg></span>], and EMBRACE [<span><span>NCT01632241</span><svg><path></path></svg></span>]), in patients with active, autoantibody-positive SLE. Patients were randomly assigned to receive belimumab (10 mg/kg per month intravenously or 200 mg per week subcutaneously) or placebo, plus standard therapy. The proportion of patients with Definitions of Remission in SLE (DORIS) remission and lupus low disease activity state (LLDAS) were analysed every 4 weeks from week 4 to week 52 for belimumab versus placebo, using modified Poisson regression adjusted for trial variance, in all patients and in subgroups per baseline SLE Disease Activity Index-2000 score (<10 or ≥10); anti-double stranded DNA positivity (yes or no); low complement 3 (C3) or C4 levels (yes or no); anti-dsDNA positivity or low C3 or C4 levels (yes and no); prednisone-equivalent dose (≤7·5 mg per day or >7·5 mg per day); antimalarial use (yes or no); and by race (Black African ancestry or African American, Asian, Indigenous American, or White).</div></div><div><h3>Findings</h3><div>Data for 3086 patients (1869 in the belimumab group and 1217 in the placebo group) were analysed. 2913 (94%) of 3086 patients were women and 173 (6%) were men, and the median age was 36 years (IQR 28–45). The proportion of patients with DORIS remission was significantly higher in the belimumab group than the placebo group at weeks 28, 48, and 52 (week 52: 148 [8%] of 1869 participants <em>vs</em> 68 [6%] of 1217 participants; risk ratio 1·51 [95% CI 1·15–1·99]; p=0·0055). The proportion of patients who attained LLDAS was higher in the belimumab group than the placebo group at weeks 8, 24, 32–52 (week 52: 322 [17%] of 1869 participants <em>vs</em> 125 [10%] of 1217 participants; 1·74 [1·44–2·12]; p<0·0001). A higher proportion of patients had DORIS remission at week 52 in the belimumab group than the placebo group among all baseline subgroups denoting high disease activity, with the exception of those on a prednisone-equivalent dose higher than 7·5 mg per day in whom there was no difference for DORIS remission with belimumab versus placebo. The proportion of patients with LLDAS was signifi","PeriodicalId":48540,"journal":{"name":"Lancet Rheumatology","volume":null,"pages":null},"PeriodicalIF":15.0,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142113577","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}
Pub Date : 2024-08-22DOI: 10.1016/S2665-9913(24)00228-5
Suzanne Arends , Arjan Vissink , Frans G M Kroese , Gwenny M Verstappen , Hendrika Bootsma
{"title":"A future for prediction and treatment of Sjögren's disease-associated lymphomas","authors":"Suzanne Arends , Arjan Vissink , Frans G M Kroese , Gwenny M Verstappen , Hendrika Bootsma","doi":"10.1016/S2665-9913(24)00228-5","DOIUrl":"10.1016/S2665-9913(24)00228-5","url":null,"abstract":"","PeriodicalId":48540,"journal":{"name":"Lancet Rheumatology","volume":null,"pages":null},"PeriodicalIF":15.0,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142056980","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}
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