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：评估复发缓解型多发性硬化（RRMS）II期临床试验中，奥瑞珠单抗（ocrelizumab）对脑部磁共振成像（MRI）评估的疾病活动度指标的起效时间，以及复发型多发性硬化（RMS）汇总III期临床试验中的复发率。
研究方法：在II期临床试验中，对接受安慰剂、奥瑞珠单抗（600mg）或肌内注射干扰素（IFN）β-1a（30μg）的RRMS患者，每月评估脑部MRI活动情况。对复发型多发性硬化（RMS）患者的汇总人群（来自III期OPERA I及OPERA II临床试验，接受奥瑞珠单抗600mg或皮下注射IFNβ-1a 44μg），分析其年复发率（ARR，涵盖不同时段）及首次复发时间。
研究结果：在RRMS患者中，与安慰剂相比，奥瑞珠单抗可在第4周时减少新发T1加权钆增强病灶数量（P=0.042）；与肌内注射IFNβ-1a相比，可在第8周时减少该类病灶数量（P<0.001）。与安慰剂及IFNβ-1a相比，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（两者P均<0.001）。在RMS患者中，与皮下注射IFNβ-1a相比，奥瑞珠单抗可在首8周内显著降低年复发率（P=0.005），并降低首次出现方案定义复发的概率（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及III期临床试验的复发率分析一致显示，分别在RRMS及RMS患者中，起始奥瑞珠单抗治疗后可快速抑制急性MRI及临床疾病活动度。
证据分类：本研究提供II级证据，证实对于RRMS及RMS患者，奥瑞珠单抗可在4周内抑制MRI活动度，并在8周内抑制临床疾病活动度。