Moloney Eoin, Mashayekhi Atefeh, Sharma Sakshi, Kontogiannis Vasileios, Ansaripour Amir, Brownlee Wallace, Paling David, Javanbakht Mehdi
Optimax Access Ltd, Southampton, United Kingdom.
Optimax Access Ltd, Rotterdam, Netherlands.
Front Neurol. 2024 Dec 6;15:1479476. doi: 10.3389/fneur.2024.1479476. eCollection 2024.
Relapsing multiple sclerosis (RMS) is a chronic, inflammatory disease of the central nervous system. Ublituximab, an anti-CD20 monoclonal antibody (mAb), is indicated for the treatment of RMS. We performed a systematic literature review (SLR) to identify randomized trials reporting the clinical efficacy and tolerability of ublituximab or comparator disease-modifying therapies (DMTs) for treatment of RMS, and assessed their comparative effects using network meta-analysis (NMA).
The SLR involved a comprehensive search across various medical databases to identify relevant studies. Included studies were randomized controlled trials (RCTs) of an adult RMS population, focusing on treatment with at least one of ublituximab, alemtuzumab, natalizumab, ocrelizumab, or ofatumumab. For outcomes included in the NMA (annualized relapse rate (ARR), confirmed disability progression (CDP), and treatment discontinuation rate), rate ratios (RR) or hazard ratios (HR), along with their 95% confidence intervals (CIs), were calculated. We performed NMA using a contrast-based random-effects model within a frequentist framework for all outcomes. Ranking probabilities among comparators, and intervention rankings for the NMA, were estimated using surface under the cumulative ranking curve (SUCRA).
We included 15 RCTs in the review. For the ARR outcome, there was no statistically significant difference between ublituximab and the other included mAbs [ofatumumab (RR 1.02 (95% CI 0.64-1.62)), natalizumab (RR 0.99 (0.59-1.65)), alemtuzumab (RR 0.86 (0.51-1.46)), and ocrelizumab (RR 0.75 (0.44-1.28))]. For CDP at 6 months, our results showed no statistically significant difference between ublituximab and the comparator mAbs [ofatumumab (HR 0.97 (0.49-1.92)), natalizumab (HR 1.13 (0.53-2.40)), alemtuzumab (HR 1.25 (0.56-2.81)), and ocrelizumab (HR 1.29 (0.57-2.90))]. For CDP at 3 and 6 months, there was no statistically significant difference between ublituximab and placebo. The all-cause treatment discontinuation rate analysis showed no significant difference between ublituximab and other mAbs, except for alemtuzumab.
Results of this SLR-informed NMA showed that there is no statistically significant difference between ublituximab and the other mAbs in terms of clinical efficacy. Additionally, the findings show that there is no statistically significant difference in discontinuation rates with the exception of the comparison with alemtuzumab, which may be attributed to its unique dosing schedule.
复发型多发性硬化症（RMS）是一种中枢神经系统的慢性炎症性疾病。乌布利昔单抗是一种抗CD20单克隆抗体（mAb），被用于治疗RMS。我们进行了一项系统文献综述（SLR），以识别报告乌布利昔单抗或对照疾病修饰疗法（DMTs）治疗RMS的临床疗效和耐受性的随机试验，并使用网络荟萃分析（NMA）评估它们的比较效果。
SLR涉及对各种医学数据库进行全面检索以识别相关研究。纳入的研究是针对成年RMS人群的随机对照试验（RCTs），重点是使用乌布利昔单抗、阿仑单抗、那他珠单抗、奥瑞珠单抗或奥法木单抗中的至少一种进行治疗。对于NMA中纳入的结局（年化复发率（ARR）、确诊的残疾进展（CDP）和治疗中断率），计算率比（RR）或风险比（HR）及其95%置信区间（CIs）。我们在频率主义框架内使用基于对比的随机效应模型对所有结局进行NMA。使用累积排名曲线下面积（SUCRA）估计比较剂之间的排名概率以及NMA的干预排名。
我们在综述中纳入了15项RCTs。对于ARR结局，乌布利昔单抗与其他纳入的mAb之间无统计学显著差异[奥法木单抗（RR 1.02（95% CI 0.64 - 1.62））、那他珠单抗（RR 0.99（0.59 - 1.65））、阿仑单抗（RR 0.86（0.51 - 1.46））和奥瑞珠单抗（RR 0.75（0.44 - 1.28））]。对于6个月时的CDP，我们的结果显示乌布利昔单抗与对照mAb之间无统计学显著差异[奥法木单抗（HR 0.97（0.49 - 1.92））、那他珠单抗（HR 1.13（0.53 - 2.40））、阿仑单抗（HR 1.25（0.56 - 2.81））和奥瑞珠单抗（HR 1.29（0.57 - 2.90））]。对于3个月和6个月时的CDP，乌布利昔单抗与安慰剂之间无统计学显著差异。全因治疗中断率分析显示，除阿仑单抗外，乌布利昔单抗与其他mAb之间无显著差异。
这项基于SLR的NMA结果表明，乌布利昔单抗与其他mAb在临床疗效方面无统计学显著差异。此外，研究结果表明，除了与阿仑单抗比较外，中断率无统计学显著差异，这可能归因于其独特的给药方案。
