Systematic literature review and network meta-analysis of cladribine tablets versus alternative disease-modifying treatments for relapsing-remitting multiple sclerosis

<b><i>Objective</i></b>: To assess the comparative efficacy and safety of cladribine tablets versus alternative disease modifying treatments (DMTs) in patients with active relapsing-remitting multiple sclerosis (RRMS), and in a subgroup with high disease activity (HRA+DAT), using systematic literature review (SLR) and network meta-analysis (NMA). <b><i>Methods</i></b>: MEDLINE, Embase, MEDLINE In-Process and CENTRAL databases were systematically searched to identify English-language publications of relevant studies of approved DMTs for RRMS. Searches were conducted from database inception to January 2017. Conference websites and trial registries were also searched. NMA considered the effects of DMTs on annualized relapse rate (ARR), confirmed disease progression (CDP), no evidence of disease activity (NEDA), and safety. <b><i>Results</i></b>: Of 10,825 articles retrieved and screened, 44 studies assessing 12 DMTs contributed to the NMA. In patients with active RRMS, cladribine tablets were associated with a significant 58% reduction in ARR versus placebo (p <b><i>Conclusion</i></b>: In this first NMA to consider cladribine tablets, ocrelizumab, and daclizumab for treatment of RRMS, cladribine tablets are a comparatively effective and safe alternative to other DMTs in both active RRMS and HRA+DAT populations.

<b><i>研究目的</i></b>：本研究旨在通过系统综述（systematic literature review, SLR）与网络荟萃分析（network meta-analysis, NMA），评估克拉屈滨片（cladribine tablets）对比其他疾病修正治疗（disease modifying treatments, DMTs）在活动性复发缓解型多发性硬化（relapsing-remitting multiple sclerosis, RRMS）患者，以及高疾病活动度亚组（HRA+DAT）中的相对疗效与安全性。<b><i>研究方法</i></b>：系统检索MEDLINE、Embase、MEDLINE In-Process及CENTRAL数据库，筛选针对复发缓解型多发性硬化获批疾病修正治疗的相关英文文献，检索时限为数据库建库至2017年1月；同时检索会议官网及试验注册库。本次网络荟萃分析评估了疾病修正治疗对年化复发率（annualized relapse rate, ARR）、确认性疾病进展（confirmed disease progression, CDP）、无疾病活动证据（no evidence of disease activity, NEDA）及安全性的影响。<b><i>研究结果</i></b>：共检索并筛选得到10825篇文献，其中44项涉及12种疾病修正治疗的研究纳入本次网络荟萃分析。在活动性复发缓解型多发性硬化患者中，相较于安慰剂，克拉屈滨片可使年化复发率显著降低58%（p <b><i>研究结论</i></b>：在这项首次将克拉屈滨片、奥瑞珠单抗（ocrelizumab）及达珠单抗（daclizumab）纳入复发缓解型多发性硬化治疗评估的网络荟萃分析中，无论在活动性复发缓解型多发性硬化患者还是高疾病活动度亚组人群中，克拉屈滨片均为相较于其他疾病修正治疗的疗效与安全性俱佳的替代治疗方案。