School of Medicine and Public Health, The University of Newcastle, Callaghan, New South Wales, Australia.
HNEHealth Libraries, Hunter New England Local Health District, New Lambton, New South Wales, Australia.
BMJ Open. 2021 Nov 2;11(11):e051509. doi: 10.1136/bmjopen-2021-051509.
Disease-modifying therapies (DMTs) are the mainstay of treatment for relapsing-remitting multiple sclerosis (RRMS). There is established evidence that DMTs are effective at reducing relapse rate and disease progression in RRMS, but there has been less consideration to the synthesis of MRI and neurocognitive outcomes, which play an increasingly important role in treatment decisions. The aim of this systematic review and network meta-analysis is to examine the relative efficacy, acceptability and tolerability of DMTs for RRMS, using MRI and neurocognitive outcomes.
We will search electronic databases, including MEDLINE, Embase and the Cochrane Central Register of Controlled Trials, with no date restrictions. We will also search the websites of international regulatory bodies for pharmaceuticals and international trial registries. We will include parallel group randomised controlled trials of DMTs including interferon beta-1a intramuscular, interferon beta-1a subcutaneous, interferon beta-1b, peginterferon beta-1a, glatiramer acetate, natalizumab, ocrelizumab, alemtuzumab, dimethyl fumarate, teriflunomide, fingolimod, cladribine, ozanimod, mitoxantrone and rituximab, either head-to-head or against placebo in adults with RRMS. Primary outcomes include efficacy (MRI outcomes including new T1/hypointense lesions and T2/hyperintense lesions) and acceptability (all-cause dropouts). Secondary outcomes include gadolinium-enhancing lesions, cerebral atrophy and tolerability (dropouts due to adverse events). Neurocognitive measures across three domains including processing speed, working memory and verbal learning will be included as exploratory outcomes. Data will be analysed using a random-effects pairwise meta-analysis and a Bayesian hierarchical random effects network meta-analysis to evaluate the efficacy, acceptability and tolerability of the included DMTs. Subgroup and sensitivity analyses will be conducted to assess the robustness of the findings. The review will be reported using the Preferred Reporting Items for Systematic Reviews incorporating Network Meta-Analyses statement.
This protocol does not require ethics approval. Results will be disseminated in a peer-reviewed academic journal.
CRD42021239630.
疾病修正疗法（DMTs）是治疗复发缓解型多发性硬化症（RRMS）的主要方法。已有充分证据表明，DMTs 可有效降低 RRMS 的复发率和疾病进展，但对于 MRI 和神经认知结果的综合考虑较少，而这些结果在治疗决策中起着越来越重要的作用。本系统评价和网络荟萃分析旨在研究 MRI 和神经认知结果的 DMTs 在 RRMS 中的相对疗效、可接受性和耐受性。
我们将检索电子数据库，包括 MEDLINE、Embase 和 Cochrane 对照试验中心注册库，不设日期限制。我们还将检索国际药品监管机构的网站和国际试验注册处。我们将纳入 DMTs 的平行组随机对照试验，包括肌内注射干扰素β-1a、皮下注射干扰素β-1a、干扰素β-1b、聚乙二醇干扰素β-1a、那他珠单抗、奥瑞珠单抗、阿仑单抗、富马酸二甲酯、特立氟胺、芬戈莫德、克拉屈滨、奥扎尼莫德、米托蒽醌和利妥昔单抗，无论是与安慰剂对照还是与其他药物对照，用于治疗 RRMS 的成年人。主要结局包括疗效（MRI 结局，包括新 T1/低信号病变和 T2/高信号病变）和可接受性（所有原因的脱落）。次要结局包括钆增强病变、脑萎缩和耐受性（因不良反应而脱落）。包括处理速度、工作记忆和言语学习在内的三个领域的神经认知测量将作为探索性结局纳入。数据将使用随机效应成对荟萃分析和贝叶斯分层随机效应网络荟萃分析进行分析，以评估纳入的 DMTs 的疗效、可接受性和耐受性。将进行亚组和敏感性分析，以评估结果的稳健性。该综述将按照包含网络荟萃分析的系统评价的首选报告项目进行报告。
本方案不需要伦理批准。研究结果将在同行评议的学术期刊上发表。
PROSPERO 注册号：CRD42021239630。
