Five-Year Safety and Efficacy Outcomes with Ofatumumab in Patients with Relapsing Multiple Sclerosis.

IF 4.8 3区医学 Q1 CLINICAL NEUROLOGY

Neurology and Therapy Pub Date : 2025-10-01 Epub Date: 2025-07-13 DOI:10.1007/s40120-025-00784-0

Stephen L Hauser, Jeffrey A Cohen, Jérôme de Sèze, Sven G Meuth, Paul S Giacomini, Jin Nakahara, Celia Oreja-Guevara, Derrick Robertson, Sibyl Wray, Alit Bhatt, Xixi Hu, Jing Xi, Rebecca Piccolo, Valentine Jehl, Roseanne Sullivan, Ibolya Boer, Heinz Wiendl, Ludwig Kappos

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引用次数: 0

Abstract

Introduction: Ofatumumab demonstrated superior efficacy and similar safety versus teriflunomide in ASCLEPIOS I/II in people with relapsing multiple sclerosis; no new safety concerns and sustained efficacy were observed up to 4 years in the open-label extension study ALITHIOS. Here, we further characterise the safety and efficacy of ofatumumab up to 5 years by discussing infection outcomes in the COVID-19 era and providing a comprehensive overview of participant disability outcomes.

Methods: Safety (N = 1969; participants who received ≥ 1 dose of ofatumumab in ASCLEPIOS I/II, APLIOS, APOLITOS, or ALITHIOS) and efficacy sets (N = 1882; participants randomised to ofatumumab [OMB-OMB] or teriflunomide [TER-OMB] in ASCLEPIOS I/II, regardless of whether they entered ALITHIOS) were analysed. Data cutoff: 25 September 2022.

Results: The exposure-adjusted incidence rates (per 100 patient-years) of adverse events (AEs, 124.65), serious AEs (4.68), serious infections (1.63), and malignancies (0.32) remained consistent with previous findings up to 5 years of follow-up, with no new safety signals identified. With ofatumumab treatment up to 5 years, > 80% of patients remained free of 6-month confirmed disability worsening (6mCDW). Annualised relapse rates (ARR) remained low, and magnetic resonance imaging (MRI) activity was almost completely suppressed with OMB-OMB through years 1-5; after switching from teriflunomide (years 2-3), pronounced reductions in ARR/MRI activity were observed with low rates sustained through years 3-5. During year 5, 9 of 10 participants in both groups were free of disease activity (NEDA-3).

Conclusion: Ofatumumab has a favourable benefit-risk profile that is sustained up to 5 years.

Trial registration: ALITHIOS (NCT03650114): https://clinicaltrials.gov/ct2/show/NCT03650114.

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Ofatumumab治疗复发性多发性硬化症患者的5年安全性和有效性

在复发性多发性硬化症患者的ASCLEPIOS I/II中，Ofatumumab显示出优于teriflunomide的疗效和相似的安全性；在开放标签扩展研究ALITHIOS中，没有观察到新的安全性问题和持续疗效长达4年。在这里，我们通过讨论COVID-19时代的感染结果并提供参与者残疾结果的全面概述，进一步表征了ofatumumab长达5年的安全性和有效性。方法：安全性(N = 1969；在ASCLEPIOS I/II、applios、APOLITOS或ALITHIOS中接受≥1剂量ofatumumab治疗的参与者和疗效组(N = 1882；在ASCLEPIOS I/II中随机分配到ofatumumab [OMB-OMB]或teriflunomide [TER-OMB]的参与者，无论他们是否进入ALITHIOS)进行分析。数据截止日期：2022年9月25日。结果：暴露调整后的不良事件发生率（每100患者年）（ae, 124.65）、严重ae（4.68）、严重感染（1.63）和恶性肿瘤（0.32）与先前随访5年的结果保持一致，未发现新的安全信号。在ofatumumab治疗长达5年的情况下，bb80 %的患者在6个月后仍无确认的残疾恶化（6mCDW）。年复发率（ARR）仍然很低，OMB-OMB在1-5年期间几乎完全抑制了磁共振成像（MRI）活动；在改用特立氟米特后（第2-3年），观察到ARR/MRI活性明显降低，但在第3-5年期间持续低率降低。在第5年，两组10名参与者中有9名没有疾病活动（NEDA-3）。结论：Ofatumumab具有持续长达5年的有利的获益-风险特征。试验注册：ALITHIOS (NCT03650114): https://clinicaltrials.gov/ct2/show/NCT03650114。

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来源期刊

Neurology and Therapy CLINICAL NEUROLOGY-

CiteScore

5.40

自引率

8.10%

发文量

103

审稿时长

6 weeks

期刊介绍： Aims and Scope Neurology and Therapy aims to provide reliable and inclusive, rapid publication for all therapy related research for neurological indications, supporting the timely dissemination of research with a global reach, to help advance scientific discovery and support clinical practice. Neurology and Therapy is an international, open access, peer reviewed, rapid publication journal dedicated to the publication of high-quality clinical (all phases), observational, real-world and health outcomes research around the discovery, development, and use of neurological and psychiatric therapies, (also covering surgery and devices). Studies relating to diagnosis, pharmacoeconomics, public health, quality of life, and patient care, management, and education are also welcomed. The journal is of interest to a broad audience of healthcare professionals and publishes original research, reviews, case reports, trial designs, communications and letters. 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