Muros-Le Rouzic Erwan, Heer Yanic, Yiu Sean, Tozzi Viola, Braune Stefan, van Hövell Philip, Bergmann Arnfin, Bernasconi Corrado, Model Fabian, Craveiro Licinio
F. Hoffmann-La Roche Ltd., Basel, Switzerland.
PricewaterhouseCoopers AG, Zürich, Switzerland.
J Cent Nerv Syst Dis. 2024 Sep 13;16:11795735241260563. doi: 10.1177/11795735241260563. eCollection 2024.
Clinical trials comparing the efficacy of ocrelizumab (OCR) with other disease-modifying therapies (DMTs) other than interferon (IFN) β-1a in relapsing multiple sclerosis (RMS) are lacking.
To compare the treatment effect of OCR vs six DMTs' (IFN β-1a, glatiramer acetate, fingolimod, dimethyl fumarate, teriflunomide, natalizumab) treatment pathways used in clinical practice by combining clinical trial and real-world data.
Patient-level data from OPERA trials and open-label extension phase, and from the German NeuroTransData (NTD) MS registry, were used to build 1:1 propensity score-matched (PSM) cohorts controlling for seven baseline covariates, including brain imaging activity. Efficacy outcomes were time to first relapse and time to 24-week confirmed disability progression over 5.5 years of follow-up. Intention-to-treat analysis using all outcome data irrespective of treatment switch was applied.
The analyses included 611 OPERA patients and 7141 NTD patients. We built 12 paired-matched cohorts (six for each outcome, two for each DMT) to compare efficacy of OCR in OPERA with each DMT treatment pathway in NTD. Post-matching, baseline covariates and PS were well balanced (standardized mean difference <.2 for all cohorts). Over 5.5 years, patients treated with OCR showed a statistically significant reduction in the risk of relapse (hazard ratios [HRs] .30 to .54) and disability progression (HRs .51 to .67) compared with all index therapies and their treatment switching pathways in NTD. Treatment switch and/or discontinuation occurred frequently in NTD cohorts.
OCR demonstrates superiority in controlling relapses and disability progression in RMS compared with real-world treatment pathways over a 5.5-year period. These analyses suggest that high-efficacy DMTs and high treatment persistence are critical to achieve greatest clinical benefit in RMS.
OPERA I (NCT01247324), OPERA II (NCT01412333).
在复发型多发性硬化症（RMS）中，缺乏将奥瑞珠单抗（OCR）与除干扰素（IFN）β-1a之外的其他疾病修饰疗法（DMTs）的疗效进行比较的临床试验。
通过整合临床试验和真实世界数据，比较奥瑞珠单抗与六种DMTs（IFNβ-1a、醋酸格拉替雷、芬戈莫德、富马酸二甲酯、特立氟胺、那他珠单抗）在临床实践中使用的治疗途径的治疗效果。
来自OPERA试验及其开放标签延长期以及德国神经传递数据（NTD）多发性硬化症登记处的患者水平数据，用于构建1:1倾向评分匹配（PSM）队列，控制七个基线协变量，包括脑成像活动。疗效结局为随访5.5年期间首次复发时间和24周确认的残疾进展时间。应用意向性分析，使用所有结局数据，无论是否发生治疗转换。
分析纳入了611例OPERA患者和7141例NTD患者。我们构建了12个配对匹配队列（每个结局6个，每个DMT 2个），以比较OPERA中奥瑞珠单抗与NTD中每种DMT治疗途径的疗效。匹配后，基线协变量和PSM得到了很好的平衡（所有队列的标准化均数差异<.2）。在5.5年期间，与NTD中的所有对照疗法及其治疗转换途径相比，接受奥瑞珠单抗治疗的患者复发风险（风险比[HRs].30至.54）和残疾进展风险（HRs.51至.67）有统计学显著降低。NTD队列中经常发生治疗转换和/或停药。
与5.5年期间的真实世界治疗途径相比，奥瑞珠单抗在控制RMS的复发和残疾进展方面显示出优越性。这些分析表明，高效DMTs和高治疗持续性对于在RMS中获得最大临床益处至关重要。
OPERA I（NCT01247324），OPERA II（NCT01412333）。
