贝里穆马布
美罗华
医学
B细胞激活因子
CD20
安慰剂
内科学
不利影响
免疫学
B细胞
胃肠病学
药理学
抗体
病理
替代医学
作者
Xavier Mariette,Francesca Barone,Chiara Baldini,Hendrika Bootsma,Kenneth L. Clark,Salvatore De Vita,David H. Gardner,Robert B. Henderson,Michael Herdman,Karoline Lerang,Prafull Mistry,Raj Punwaney,Raphaèle Séror,John H. Stone,Paul L A van Daele,André van Maurik,Nicolas Wisniacki,David A. Roth,Paul P. Tak
出处
期刊:JCI insight
[American Society for Clinical Investigation]
日期:2022-12-08
卷期号:7 (23)
被引量:23
标识
DOI:10.1172/jci.insight.163030
摘要
BACKGROUNDPrimary Sjögren's syndrome (pSS) is characterized by B cell hyperactivity and elevated B-lymphocyte stimulator (BLyS). Anti-BLyS treatment (e.g., belimumab) increases peripheral memory B cells; decreases naive, activated, and plasma B cell subsets; and increases stringency on B cell selection during reconstitution. Anti-CD20 therapeutics (e.g., rituximab) bind and deplete CD20-expressing B cells in circulation but are less effective in depleting tissue-resident CD20+ B cells. Combined, these 2 mechanisms may achieve synergistic effects.METHODSThis 68-week, phase II, double-blind study (GSK study 201842) randomized 86 adult patients with active pSS to 1 of 4 arms: placebo, s.c. belimumab, i.v. rituximab, or sequential belimumab + rituximab.RESULTSOverall, 60 patients completed treatment and follow-up until week 68. The incidence of adverse events (AEs) and drug-related AEs was similar across groups. Infections/infestations were the most common AEs, and no serious infections of special interest occurred. Near-complete depletion of minor salivary gland CD20+ B cells and a greater and more sustained depletion of peripheral CD19+ B cells were observed with belimumab + rituximab versus monotherapies. With belimumab + rituximab, reconstitution of peripheral B cells occurred, but it was delayed compared with rituximab. At week 68, mean (± standard error) total EULAR Sjögren's syndrome disease activity index scores decreased from 11.0 (1.17) at baseline to 5.0 (1.27) for belimumab + rituximab and 10.4 (1.36) to 8.6 (1.57) for placebo.CONCLUSIONThe safety profile of belimumab + rituximab in pSS was consistent with the monotherapies. Belimumab + rituximab induced enhanced salivary gland B cell depletion relative to the monotherapies, potentially leading to improved clinical outcomes.TRIAL REGISTRATIONClinicalTrials.gov NCT02631538.FUNDINGFunding was provided by GSK.
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