Department of Neuroscience, Central Clinical School, Monash University, Melbourne, Victoria, Australia.
Department of Medicine and Melbourne Brain Centre, The Royal Melbourne Hospital, University of Melbourne, Melbourne, Victoria, Australia.
Eur J Neurol. 2022 Apr;29(4):1082-1090. doi: 10.1111/ene.14824. Epub 2021 May 6.
Reaching Expanded Disability Status Scale (EDSS) ≥7.0 represents the requirement for a wheelchair. Here we (i) assess the effect of ocrelizumab on time to EDSS ≥7.0 over the ORATORIO (NCT01194570) double-blind and extended controlled periods (DBP+ECP), (ii) quantify likely long-term benefits by extrapolating results, and (iii) assess the plausibility of extrapolations using an independent real-world cohort (MSBase registry; ACTRN12605000455662).
Post hoc analyses assessing time to 24-week confirmed EDSS ≥7.0 in two cohorts of patients with primary progressive multiple sclerosis (baseline EDSS 3.0-6.5) were investigated in ORATORIO and MSBase.
In the ORATORIO DBP+ECP, ocrelizumab reduced the risk of 24-week confirmed EDSS ≥7.0 (hazard ratio = 0.54, 95% confidence interval [CI]: 0.31-0.92; p = 0.022). Extrapolated median time to 24-week confirmed EDSS ≥7.0 was 12.1 and 19.2 years for placebo and ocrelizumab, respectively (7.1-year delay [95% CI: -4.3 to 18.4]). In MSBase, the median time to 24-week confirmed EDSS ≥7.0 was 12.4 years.
Compared with placebo, ocrelizumab significantly delayed time to 24-week confirmed wheelchair requirement in ORATORIO. The plausibility of the extrapolated median time to reach this milestone in the placebo group was supported by observed real-world data from MSBase. Extrapolated benefits for ocrelizumab over placebo could represent a truly meaningful delay in loss of ambulation and independence.
达到扩展残疾状况量表（EDSS）≥7.0 表示需要使用轮椅。在这里，我们（i）评估奥瑞珠单抗在 ORATORIO（NCT01194570）双盲和扩展对照期（DBP+ECP）期间对 EDSS≥7.0 的时间影响，（ii）通过外推结果量化可能的长期获益，以及（iii）使用独立的真实世界队列（MSBase 登记处；ACTRN12605000455662）评估外推的合理性。
对 ORATORIO 和 MSBase 中基线 EDSS 为 3.0-6.5 的原发性进展性多发性硬化症（PPMS）患者的两个队列进行了 24 周确认的 EDSS≥7.0 的时间的事后分析。
在 ORATORIO DBP+ECP 中，奥瑞珠单抗降低了 24 周确认的 EDSS≥7.0 的风险（风险比=0.54，95%置信区间[CI]：0.31-0.92；p=0.022）。外推的中位时间至 24 周确认的 EDSS≥7.0 分别为安慰剂和奥瑞珠单抗组的 12.1 年和 19.2 年（7.1 年延迟[95%CI：-4.3 至 18.4]）。在 MSBase 中，24 周确认的 EDSS≥7.0 的中位时间为 12.4 年。
与安慰剂相比，奥瑞珠单抗在 ORATORIO 中显著延迟了 24 周确认的轮椅需求时间。MSBase 的真实世界数据支持了安慰剂组中位时间达到这一里程碑的外推合理性。奥瑞珠单抗相对于安慰剂的外推获益可能代表了真正有意义的步行和独立能力丧失的延迟。
