Long-term safety and efficacy of dimethyl fumarate for up to 13 years in patients with relapsing-remitting multiple sclerosis: Final ENDORSE study results.

Multiple sclerosis (Houndmills, Basingstoke, England) Pub Date : 2022-04-01 Epub Date: 2021-09-01 DOI:10.1177/13524585211037909

Ralf Gold, Douglas L Arnold, Amit Bar-Or, Robert J Fox, Ludwig Kappos, Oksana Mokliatchouk, Xiaotong Jiang, Jennifer Lyons, Shivani Kapadia, Catherine Miller

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引用次数: 24

Abstract

Background: Dimethyl fumarate (DMF) demonstrated favorable benefit-risk in relapsing-remitting multiple sclerosis (RRMS) patients in phase-III DEFINE and CONFIRM trials, and ENDORSE extension.

Objective: The main aim of this study is assessing DMF safety/efficacy up to 13 years in ENDORSE.

Methods: Randomized patients received DMF 240 mg twice daily or placebo (PBO; Years 0-2), then DMF (Years 3-10; continuous DMF/DMF or PBO/DMF); maximum follow-up (combined studies), 13 years.

Results: By January 2020, 1736 patients enrolled/dosed in ENDORSE (median follow-up 8.76 years (ENDORSE range: 0.04-10.98) in DEFINE/CONFIRM and ENDORSE); 52% treated in ENDORSE for ⩾6 years. Overall, 551 (32%) patients experienced serious adverse events (mostly multiple sclerosis (MS) relapse or fall; one progressive multifocal leukoencephalopathy); 243 (14%) discontinued treatment due to adverse events (4% gastrointestinal (GI) disorders). Rare opportunistic infections, malignancies, and serious herpes zoster occurred, irrespective of lymphocyte count. For DMF/DMF (n = 501), overall annualized relapse rate (ARR) remained low (0.143 (95% confidence interval (CI), 0.120-0.169)), while for PBO/DMF (n = 249), ARR decreased after initiating DMF and remained low throughout (ARR 0-2 years, 0.330 (95% CI, 0.266-0.408); overall ARR (ENDORSE, 0.151 (95% CI, 0.118-0.194)). Over 10 years, 72% DMF/DMF and 73% PBO/DMF had no 24-week confirmed disability worsening.

Conclusion: Sustained DMF safety/efficacy was observed in patients followed up to 13 years, supporting DMF's positive benefit/risk profile for long-term RRMS treatment.

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富马酸二甲酯治疗复发缓解型多发性硬化症长达13年的长期安全性和有效性:最终的背书研究结果

背景:富马酸二甲酯(DMF)在复发-缓解型多发性硬化症(RRMS)患者的iii期DEFINE和CONFIRM试验中显示出有利的获益-风险。目的:本研究的主要目的是评估DMF在背书治疗中长达13年的安全性/有效性。方法:随机患者接受DMF 240 mg，每日2次或安慰剂(PBO;0-2年级)，然后是DMF(3-10年级;连续DMF/DMF或PBO/DMF);最长随访(联合研究)13年。结果:截至2020年1月，在DEFINE/CONFIRM和背书中，1736名患者入组/给药(中位随访8.76年(背书范围:0.04-10.98));52%在背书中接受了小于6年的治疗。总体而言，551例(32%)患者出现严重不良事件(主要是多发性硬化症(MS)复发或跌倒;1例进行性多灶性脑白质病);243例(14%)因不良事件(4%胃肠道疾病)停止治疗。发生罕见的机会性感染、恶性肿瘤和严重的带状疱疹，与淋巴细胞计数无关。对于DMF/DMF (n = 501)，总体年化复发率(ARR)仍然很低(0.143(95%可信区间(CI)， 0.120-0.169))，而对于PBO/DMF (n = 249)， ARR在开始DMF后下降，并在整个过程中保持较低(ARR 0-2年，0.330 (95% CI, 0.266-0.408);总ARR(背书，0.151 (95% CI, 0.118-0.194))。在10年中，72%的DMF/DMF和73%的PBO/DMF在24周内没有确认的残疾恶化。结论:在随访13年的患者中观察到持续的DMF安全性/有效性，支持DMF对长期RRMS治疗的积极益处/风险概况。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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Multiple sclerosis (Houndmills, Basingstoke, England)

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