Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
Department of Pharmacology and Clinical Neuroscience, Section for Neurology, Umeå University, Umeå, Sweden.
JAMA Neurol. 2018 Mar 1;75(3):320-327. doi: 10.1001/jamaneurol.2017.4011.
Comparative real-world effectiveness studies of initial disease-modifying treatment (DMT) choices for relapsing-remitting multiple sclerosis (RRMS) that include rituximab are lacking.
To assess the effectiveness and drug discontinuation rates of rituximab among patients with newly diagnosed RRMS compared with injectable DMTs, dimethyl fumarate, fingolimod, or natalizumab.
DESIGN, SETTING, AND PATIENTS: This retrospective cohort study used prospectively collected data to examine specialized care of 2 Swedish county-based community samples of patients with RRMS. Patients with RRMS who received diagnoses from January 1, 2012, to October 31, 2015, who resided in Stockholm or Västerbotten Counties were identified from a Swedish multiple sclerosis registry.
All reasons for drug discontinuation of initial treatment choice (main outcome) and specific reasons for switching (secondary outcomes) were analyzed with multivariable Cox regression, including propensity scores.
Among 494 patients (median [interquartile range] age, 34.4 [27.4-43.4] years; 158 men [32.0%]), 215 received an injectable DMT (43.5%); 86 (17.4%), dimethyl fumarate; 17 (3.4%), fingolimod; 50 (10.1%), natalizumab; 120 (24.3%), rituximab; and 6 (1.2%), other DMT. Regional preferences were pronounced, with 42 of 52 (81%) and 78 of 442 (18%) receiving rituximab in Västerbotten and Stockholm, respectively. The annual discontinuation rate for rituximab, injectable DMTs, dimethyl fumarate, fingolimod, and natalizumab were 0.03, 0.53, 0.32, 0.38, and 0.29, respectively. Continued disease activity was the main reason for discontinuation of injectable DMTs, dimethyl fumarate, and fingolimod; positive John Cunningham virus serology results were the main reason for discontinuation of natalizumab. Rate of clinical relapses and/or neuroradiologic disease activity were significantly lower for rituximab compared with injectable DMTs and dimethyl fumarate, with a tendency for lower relapse rates also compared with natalizumab and fingolimod. The annual discontinuation rate of initial treatment choice was significantly lower in Västerbotten compared with Stockholm (0.09 and 0.37, respectively).
Rituximab was superior to all other DMT in terms of drug discontinuation and displayed better clinical efficacy compared with injectable DMTs and dimethyl fumarate with borderline significance compared with natalizumab and fingolimod. The county where rituximab constituted the main initial treatment choice displayed better outcomes in most measured variables. Collectively, our findings suggest that rituximab performs better than other commonly used DMTs in patients with newly diagnosed RRMS.
缺乏比较利妥昔单抗与其他用于治疗复发缓解型多发性硬化症（RRMS）的初始疾病修正治疗（DMT）选择的真实世界疗效研究。
评估与注射用 DMT、二甲基富马酸、芬戈莫德或那他珠单抗相比，利妥昔单抗在新诊断的 RRMS 患者中的有效性和停药率。
设计、设置和患者：这项回顾性队列研究使用前瞻性收集的数据，对瑞典 2 个基于县的社区 RRMS 患者的专门护理进行了研究。从瑞典多发性硬化症登记处确定了 2012 年 1 月 1 日至 2015 年 10 月 31 日期间在斯德哥尔摩或韦斯特博滕县居住的、被诊断为 RRMS 的患者。
用多变量 Cox 回归（包括倾向评分）分析了所有初始治疗选择的停药原因（主要结局）和特定的换药原因（次要结局）。
在 494 名患者（中位数[四分位间距]年龄，34.4[27.4-43.4]岁；158 名男性[32.0%]）中，215 名接受了注射用 DMT（43.5%）；86 名（17.4%）接受二甲基富马酸治疗；17 名（3.4%）接受芬戈莫德治疗；50 名（10.1%）接受那他珠单抗治疗；120 名（24.3%）接受利妥昔单抗治疗；6 名（1.2%）接受其他 DMT。地域偏好明显，52 名患者中有 42 名（81%）和 442 名患者中有 78 名（18%）分别在韦斯特博滕和斯德哥尔摩接受利妥昔单抗治疗。利妥昔单抗、注射用 DMT、二甲基富马酸、芬戈莫德和那他珠单抗的年停药率分别为 0.03、0.53、0.32、0.38 和 0.29。继续的疾病活动是注射用 DMT、二甲基富马酸和芬戈莫德停药的主要原因；阳性约翰·坎宁安病毒血清学结果是那他珠单抗停药的主要原因。与注射用 DMT 和二甲基富马酸相比，利妥昔单抗的临床复发和/或神经放射学疾病活动率显著降低，与那他珠单抗和芬戈莫德相比，复发率也有降低的趋势。与斯德哥尔摩相比，韦斯特博滕的初始治疗选择的年停药率显著降低（分别为 0.09 和 0.37）。
与其他 DMT 相比，利妥昔单抗在停药方面更具优势，与注射用 DMT 和二甲基富马酸相比，在临床疗效方面也具有优势，与那他珠单抗和芬戈莫德相比，优势具有边缘统计学意义。利妥昔单抗作为主要初始治疗选择的县在大多数测量变量中显示出更好的结果。总的来说，我们的发现表明，在新诊断的 RRMS 患者中，利妥昔单抗比其他常用的 DMT 更有效。
