Data from: Onset of clinical and MRI efficacy of ocrelizumab in relapsing multiple sclerosis

Objective: To assess the onset of ocrelizumab efficacy on brain magnetic
resonance imaging (MRI) measures of disease activity in the Phase II study
in relapsing-remitting multiple sclerosis (RRMS), and relapse rate in the
pooled Phase III studies in relapsing multiple sclerosis (RMS). Methods:
Brain MRI activity was determined in the Phase II trial at monthly
intervals in patients with RRMS receiving placebo, ocrelizumab (600 mg),
or intramuscular interferon (IFN) β-1a (30 μg). Annualized relapse rate
(ARR; over various epochs) and time to first relapse were analyzed in the
pooled population of the Phase III OPERA I and OPERA II trials in patients
with RMS receiving ocrelizumab (600 mg) or subcutaneous IFN β-1a (44 μg).
Results: In patients with RRMS, ocrelizumab reduced the number of new T1
gadolinium-enhancing lesions by Week 4 vs placebo (p=0.042) and by Week 8
vs intramuscular IFN β-1a (p<0.001). Ocrelizumab also reduced the
number of new or enlarging T2 lesions appearing between Weeks 4 and 8 vs
both placebo and IFN β-1a (both p<0.001). In patients with RMS,
ocrelizumab significantly reduced ARR (p=0.005), and the probability of
time to first protocol-defined relapse (p=0.014) vs subcutaneous IFN β-1a
within the first 8 weeks. Conclusion: Epoch analysis of MRI-measured
lesion activity in the Phase II study and relapse rate in the Phase III
studies consistently revealed a rapid suppression of acute MRI and
clinical disease activity following treatment initiation with ocrelizumab
in patients with RRMS and RMS, respectively. Classification of evidence:
This study provides Class II evidence that for patients with RRMS and RMS,
ocrelizumab suppressed MRI activity within 4 weeks and clinical disease
activity within 8 weeks.

研究目的：评估奥瑞珠单抗（ocrelizumab）在复发缓解型多发性硬化（relapsing-remitting multiple sclerosis, RRMS）II期临床试验中，对脑部磁共振成像（MRI）疾病活动度指标的疗效起效特征，以及在复发型多发性硬化（relapsing multiple sclerosis, RMS）汇总III期临床试验中的复发率情况。
研究方法：在该II期临床试验中，对接受安慰剂、奥瑞珠单抗（600 mg）或肌内注射干扰素（IFN）β-1a（30 μg）的RRMS患者，每月一次评估脑部MRI活动情况。对汇总的III期OPERA I与OPERA II临床试验中，接受奥瑞珠单抗（600 mg）或皮下注射IFN β-1a（44 μg）的RMS患者队列，分析其年复发率（annualized relapse rate, ARR；涵盖不同治疗时段）及首次复发时间。
研究结果：在RRMS患者中，相较于安慰剂组，奥瑞珠单抗可在治疗第4周时减少新发T1加权钆增强病灶数量（P=0.042）；相较于肌内注射IFN β-1a组，可在第8周时减少该类病灶数量（P<0.001）。相较于安慰剂组与IFN β-1a组，奥瑞珠单抗还可减少第4周至第8周间出现的新发或扩大的T2加权病灶数量（两组P值均<0.001）。在RMS患者中，相较于皮下注射IFN β-1a组，奥瑞珠单抗可在治疗前8周内显著降低年复发率（P=0.005），并降低首次达到方案预设复发的概率（P=0.014）。
研究结论：对II期临床试验的MRI病灶活动度时段分析，以及III期临床试验的复发率分析结果一致显示：在RRMS与RMS患者中，分别启动奥瑞珠单抗治疗后，可快速抑制急性影像学与临床疾病活动度。
证据分级：本研究提供II级证据，表明针对RRMS与RMS患者，奥瑞珠单抗可在4周内抑制MRI疾病活动度，并在8周内抑制临床疾病活动度。