Treatment effectiveness of alemtuzumab compared with natalizumab, fingolimod, and interferon beta in relapsing-remitting multiple sclerosis: a cohort study
Treatment effectiveness of alemtuzumab compared with natalizumab, fingolimod, and interferon beta in relapsing-remitting multiple sclerosis: a cohort study
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DOI：
10.1016/s1474-4422(17)30007-8
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发表时间：
2017-04-01
期刊：
影响因子：
48
通讯作者：
Coles, Alasdair
中科院分区：
文献类型：
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作者：
Kalincik, Tomas;Brown, J. William L.;Coles, Alasdair
阿仑单抗是一种抗CD 52抗体，已被证明在治疗复发缓解型多发性硬化症方面比干扰素β-1a更有效，但其相对于更有效的免疫疗法的疗效尚不清楚。我们比较了阿仑单抗与那他珠单抗、芬戈莫德和干扰素β在复发缓解型多发性硬化症患者中治疗长达5 years.Methods的有效性，在这项国际队列研究中，我们使用了来自MSBase和其他6个队列的复发缓解型多发性硬化症倾向匹配患者的数据。纵向临床数据来自21个国家的71个MSBase中心以及英国和德国的6个非MSBase中心，时间为2015年11月1日至2016年6月30日。关键入选标准为确诊为复发缓解型多发性硬化症，暴露于研究治疗之一（阿仑单抗，干扰素β，芬戈莫德或那他珠单抗），年龄65岁或以下，扩展残疾状态量表（EDSS）评分6.5或更低，自首次多发性硬化症症状起不超过10年。主要终点为年复发率。次要终点是复发、残疾累积和残疾改善事件的累积风险。我们比较了复发率与负二项模型，并估计累积风险与条件比例风险models.Findings患者之间的治疗1994年8月1日，2016年6月30日。队列包括189例接受Alemtuzumab治疗的患者，2155例接受干扰素β治疗的患者，828例接受芬戈莫德治疗的患者和1160例接受那他珠单抗治疗的患者。阿仑单抗的年复发率低于干扰素β（0.19 [95%CI 0.14-0.23] vs 0.53 [0.46-0.61]，p
Background Alemtuzumab, an anti-CD52 antibody, is proven to be more efficacious than interferon beta-1a in the treatment of relapsing-remitting multiple sclerosis, but its efficacy relative to more potent immunotherapies is unknown. We compared the effectiveness of alemtuzumab with natalizumab, fingolimod, and interferon beta in patients with relapsing-remitting multiple sclerosis treated for up to 5 years.Methods In this international cohort study, we used data from propensity-matched patients with relapsing-remitting multiple sclerosis from the MSBase and six other cohorts. Longitudinal clinical data were obtained from 71 MSBase centres in 21 countries and from six non-MSBase centres in the UK and Germany between Nov 1, 2015, and June 30, 2016. Key inclusion criteria were a diagnosis of definite relapsing-remitting multiple sclerosis, exposure to one of the study therapies (alemtuzumab, interferon beta, fingolimod, or natalizumab), age 65 years or younger, Expanded Disability Status Scale (EDSS) score 6.5 or lower, and no more than 10 years since the first multiple sclerosis symptom. The primary endpoint was annualised relapse rate. The secondary endpoints were cumulative hazards of relapses, disability accumulation, and disability improvement events. We compared relapse rates with negative binomial models, and estimated cumulative hazards with conditional proportional hazards models.Findings Patients were treated between Aug 1, 1994, and June 30, 2016. The cohorts consisted of 189 patients given alemtuzumab, 2155 patients given interferon beta, 828 patients given fingolimod, and 1160 patients given natalizumab. Alemtuzumab was associated with a lower annualised relapse rate than interferon beta (0.19 [95% CI 0.14-0.23] vs 0.53 [0.46-0.61], p