COMBAT-MS: A Population-Based Observational Cohort Study Addressing the Benefit–Risk Balance of Multiple Sclerosis Therapies Compared with Rituximab

IF 8.1 1区医学 Q1 CLINICAL NEUROLOGY Annals of Neurology Pub Date : 2024-06-25 DOI:10.1002/ana.27012

Fredrik Piehl MD, PhD, Peter Alping MD, PhD, Suvi Virtanen MSc, Simon Englund MSc, Joachim Burman MD, PhD, Katharina Fink MD, PhD, Anna Fogdell-Hahn PhD, Martin Gunnarsson MD, PhD, Jan Hillert MD, PhD, Annette Langer-Gould MD, PhD, Jan Lycke MD, PhD, Johan Mellergård MD, PhD, Petra Nilsson MD, PhD, Tomas Olsson MD, PhD, Jonatan Salzer MD, PhD, Anders Svenningsson MD, PhD, Thomas Frisell PhD

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Abstract

Objective

To assess comparative effectiveness, safety, and tolerability of off-label rituximab, compared with frequently used therapies approved for multiple sclerosis (MS).

Methods

A Swedish cohort study of persons with relapsing–remitting MS, age 18 to 75 years at inclusion and with a first therapy start or a first therapy switch between 2011 and 2018. Low-dose rituximab was compared with MS-approved therapies. Primary outcomes were proportions with 12 months confirmed disability worsening and change in MS Impact Scale-29 (MSIS-29) scores, respectively. Secondary endpoints included relapses, therapy discontinuation, and serious adverse events. Analyses used an intention-to-treat approach and were adjusted for demographics, MS features, and health characteristics.

Results

We included 2,449 participants as first therapy start and 2,463 as first therapy switch. Proportions with disability worsening at 3 years were 9.1% for rituximab as first therapy and 5.1% after therapy switch, with no differences to MS-approved comparators. Worsening on rituximab was mostly independent of relapses. MSIS-29 with rituximab at 3 years improved by 1.3/8.4 points (physical/psychological) for first disease-modifying therapy (DMT) and 0.4/3.6 for DMT switch, and was mostly similar across therapies. Rituximab had lower relapse rates and higher therapy persistence in both groups. The rate of hospital-treated infections was higher with rituximab after a therapy switch, but not as a first therapy.

Interpretation

This population-based real-world cohort study found low rates of disability progression, mostly independent of relapses, and without significant differences between rituximab and MS-approved comparators. Rituximab led to lower rates of inflammatory activity and higher treatment persistence, but was associated with an increased rate of serious infections. ANN NEUROL 2024;96:678–693

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COMBAT-MS：一项基于人群的观察性队列研究，探讨多发性硬化症疗法与利妥昔单抗相比的效益-风险平衡。

目的评估标签外利妥昔单抗与多发性硬化症（MS）常用疗法的有效性、安全性和耐受性的比较：一项瑞典队列研究，研究对象为复发性缓解型多发性硬化症患者，纳入时年龄为18至75岁，在2011年至2018年间首次开始治疗或首次更换治疗方案。低剂量利妥昔单抗与多发性硬化症批准疗法进行了比较。主要结果分别是12个月内确认残疾恶化的比例和MS影响量表-29（MSIS-29）评分的变化。次要终点包括复发、停药和严重不良事件。分析采用意向治疗方法，并对人口统计学、多发性硬化症特征和健康特征进行了调整：我们纳入了2449名首次接受治疗的患者和2463名首次转换治疗的患者。首次接受利妥昔单抗治疗的患者3年后出现残疾恶化的比例为9.1%，转换治疗方案后为5.1%，与多发性硬化症批准的比较药物无差异。利妥昔单抗治疗后的病情恶化大多与复发无关。首次使用利妥昔单抗治疗3年后，MSIS-29改善了1.3/8.4分（生理/心理），换用DMT后改善了0.4/3.6分，不同疗法的改善情况基本相似。两组患者中，利妥昔单抗的复发率较低，治疗持续率较高。利妥昔单抗在转换疗法后的医院治疗感染率较高，但不作为第一种疗法：这项基于人群的真实世界队列研究发现，残疾进展率较低，主要与复发无关，且利妥昔单抗与多发性硬化症批准的比较药之间无显著差异。利妥昔单抗的炎症活动率较低，治疗持续率较高，但与严重感染率增加有关。ann neurol 2024。

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来源期刊

Annals of Neurology 医学-临床神经学

CiteScore

18.00

自引率

1.80%

发文量

270

审稿时长

3-8 weeks

期刊介绍： Annals of Neurology publishes original articles with potential for high impact in understanding the pathogenesis, clinical and laboratory features, diagnosis, treatment, outcomes and science underlying diseases of the human nervous system. Articles should ideally be of broad interest to the academic neurological community rather than solely to subspecialists in a particular field. Studies involving experimental model system, including those in cell and organ cultures and animals, of direct translational relevance to the understanding of neurological disease are also encouraged.

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