Heesen Christoph, Röver Christian, Salem Susanna, Heinz Judith, Chard Declan, Rio Jordi, Fittipaldo Andrea V, Lehnert Thomas, Köpke Sascha, Solari Alessandra, Sormani Maria Pia, Friede Tim, Rahn Anne C
Institute of Neuroimmunology and Multiple Sclerosis (INIMS), University Medical Center, Hamburg, Germany Department of Neurology, University Medical Center, Hamburg, Germany.
Department of Medical Statistics, University Medical Center Göttingen, Göttingen, Germany.
Mult Scler J Exp Transl Clin. 2024 Oct 24;10(4):20552173241274618. doi: 10.1177/20552173241274618. eCollection 2024 Oct-Dec.
This meta-analysis aimed to assess the treatment effects of immunotherapies in subgroups of adults with clinically isolated syndrome or relapsing forms of multiple sclerosis (MS) and the effect of potential treatment effect modifiers (TEMs).
Phase 2 and 3 RCTs with a placebo comparator were analyzed. Risk of bias was assessed. Random-effects meta-analyses were conducted to summarize treatment effects within subgroups and differences in treatment effects between subgroups.
Thirty-one studies were included. Age < 40 years was the strongest TEM for relapse rate across DMTs with a ratio of rate ratios (RRR) of 1.44 (95% CI 1.09-1.90; 7 studies). Disability progression was influenced by age (ratio of hazard ratios, RHR 1.59, 95% CI 1.11-2.29; 4 studies). Dichotomizing patients based on EDSS cut-offs (EDSS 2.0 and 3.0) also showed a significantly higher benefit for those less disabled for relapse rate (RRR 1.35, CI 1.03-1.76; 8 studies). Sex, baseline MRI parameters, previous immunotherapy, and clinical presentation showed no effect in this meta-analysis.
Age < 40 is a robust TEM for a lower relapse rate as well as less disability progression across six MS immunotherapies. Additionally, a lower baseline EDSS was predictive of the relapse rate.
本荟萃分析旨在评估免疫疗法对患有临床孤立综合征或复发型多发性硬化症（MS）的成年亚组患者的治疗效果，以及潜在治疗效果修饰因素（TEMs）的影响。
分析了设有安慰剂对照的2期和3期随机对照试验（RCT）。评估了偏倚风险。进行随机效应荟萃分析，以总结亚组内的治疗效果以及亚组间治疗效果的差异。
纳入了31项研究。年龄<40岁是各类疾病修正治疗（DMTs）中复发率最强的TEM，率比（RRR）为1.44（95%置信区间1.09 - 1.90；7项研究）。残疾进展受年龄影响（风险比，RHR 1.59，95%置信区间1.11 - 2.29；4项研究）。根据扩展残疾状态量表（EDSS）临界值（EDSS 2.0和3.0）对患者进行二分法分析，结果还显示，残疾程度较轻的患者在复发率方面获益显著更高（RRR 1.35，置信区间1.03 - 1.76；8项研究）。在本荟萃分析中，性别、基线MRI参数、既往免疫治疗和临床表现均未显示出影响。
年龄<40岁是六种MS免疫疗法中复发率较低以及残疾进展较少的有力TEM。此外，较低的基线EDSS可预测复发率。
