伊那鲁单抗对斯尤金病患者的安全性和有效性:一项随机、安慰剂对照、2b 期剂量范围研究的 52 周结果。

IF 11.4 1区 医学 Q1 RHEUMATOLOGY
Thomas Dörner, Simon J Bowman, Robert Fox, Xavier Mariette, Athena Papas, Thomas Grader-Beck, Benjamin A Fisher, Filipe Barcelos, Salvatore De Vita, Hendrik Schulze-Koops, Robert J Moots, Guido Junge, Janice Woznicki, Monika Sopala, Alexandre Avrameas, Wen-Lin Luo, Wolfgang Hueber
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引用次数: 0

摘要

目的报告伊那鲁单抗在斯琼氏症(SjD)患者中进行的为期52周的2b期剂量摸底研究的安全性和有效性:患者随机接受(1:1:1:1:1)伊那鲁单抗(5、50或300毫克)或安慰剂皮下注射,每4周一次,直至第24周(治疗期[TP]1)。第24周时,服用300毫克的患者被重新随机分配为继续服用300毫克或服用安慰剂至第52周(治疗期[TP2]),服用安慰剂的患者则转为服用150毫克的伊那鲁单抗,而服用5毫克和50毫克的患者则直接进入治疗后安全随访。提前终止治疗或完成治疗的患者进入安全随访(≥20周):在 TP1 期间,190 名患者接受了随机治疗(安慰剂=49 人,5 毫克=47 人,50 毫克=47 人,300 毫克=47 人)。在这 190 名患者中,90 人(47.4%;43 人继续服用 300 毫克,47 人服用安慰剂)进入 TP2,81/90 人(90.0%)完成了研究治疗。到第 52 周时,继续服用 300 毫克 TP2 的患者疗效持续(ESSDAI、ESSPRI、PaGA、PhGA 与第 24 周相比的变化分别为:-1.45、-0.46、-4.69、-6.86)。300 毫克组的刺激性唾液流速和自身抗体水平在数值上有所改善。除注射部位反应外,治疗引发的不良反应与剂量无关。在治疗后随访期间,有3名患者出现了中性粒细胞计数减少的情况(根据实验室列表,CTCAE v4.03为3级),分别发生在最后一次使用伊阿鲁单抗后的3.5个月、5.5个月和3个月。除了一次偶然发现的无症状巨细胞病毒感染(IgM+)外,其余均与感染无关:结论:在SjD患者中,伊阿鲁单抗300毫克的疗效持续到第52周,并且在两年的随访中具有良好的安全性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Safety and Efficacy of Ianalumab in Patients With Sjögren's Disease: 52-Week Results From a Randomized, Placebo-Controlled, Phase 2b Dose-Ranging Study.

Objective: To report 52-week safety and efficacy of ianalumab from phase 2b dose-finding study in patients with Sjögren's disease (SjD).

Methods: Patients randomly received (1:1:1:1) ianalumab (5, 50, or 300 mg) or placebo subcutaneously every 4 weeks till week 24 (treatment period [TP]1). At week 24, patients on 300 mg were re-randomized to continue 300 mg or receive placebo till week 52 (TP2), patients on placebo were switched to ianalumab 150 mg, while patients on 5 and 50 mg directly entered post treatment safety follow-up. Patients who discontinued treatment early or completed treatment entered safety follow-up (≥20 weeks).

Results: During TP1, 190 patients were randomized (placebo=49, 5 mg=47, 50 mg=47, 300 mg=47). Of these 190 patients, 90 (47.4 %; 43 continued 300 mg and 47 received placebo) entered TP2, and 81/90 (90.0%) completed the study treatment. By week 52, efficacy was sustained in patients who continued 300 mg in TP2 (ESSDAI, ESSPRI, PaGA, PhGA change from week 24: -1.45, -0.46, -4.69, -6.86, respectively). Stimulated salivary flow rates and autoantibody levels numerically improved in the 300 mg group. Treatment-emergent adverse events were not dose-dependent, except for injection-site reactions. Cases of decreased neutrophil counts (CTCAE v4.03 grade 3 according to laboratory listings) were observed in 3 patients during the post-treatment follow-up, occurring at 3.5, 5.5, and 3 months, after the last ianalumab administration. None were associated with infection except one incidental finding of asymptomatic cytomegalovirus infection (IgM+).

Conclusion: In patients with SjD, ianalumab 300 mg demonstrated sustained efficacy through week 52 and a favorable safety profile up to two years of follow-up.

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来源期刊
Arthritis & Rheumatology
Arthritis & Rheumatology RHEUMATOLOGY-
CiteScore
20.90
自引率
3.00%
发文量
371
期刊介绍: Arthritis & Rheumatology is the official journal of the American College of Rheumatology and focuses on the natural history, pathophysiology, treatment, and outcome of rheumatic diseases. It is a peer-reviewed publication that aims to provide the highest quality basic and clinical research in this field. The journal covers a wide range of investigative areas and also includes review articles, editorials, and educational material for researchers and clinicians. Being recognized as a leading research journal in rheumatology, Arthritis & Rheumatology serves the global community of rheumatology investigators and clinicians.
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