Safety of ocrelizumab in patients with relapsing and primary progressive multiple sclerosis

Objective: To report safety of ocrelizumab (OCR) up to 7 years in patients
with relapsing multiple sclerosis (RMS) and primary progressive multiple
sclerosis (PPMS) enrolled in clinical trials or treated in real-world
postmarketing settings. Methods: Safety analyses are based on integrated
clinical and laboratory data for all patients who received OCR in 11
clinical trials, including the controlled treatment and open-label
extension (OLE) periods of the phase 2 and 3 trials, plus the phase 3b
trials VELOCE, CHORDS, CASTING, OBOE, ENSEMBLE, CONSONANCE, and LIBERTO.
For selected adverse events (AEs), additional postmarketing data were
used. Incidence rates of serious infections and malignancies were
contextualized using multiple epidemiologic sources. Results: At data
cut-off (January 2020), 5,680 patients with multiple sclerosis (MS)
received OCR (18,218 patient years [PY] of exposure) in clinical trials.
Rates per 100 PY (95% CI) of AEs (248; 246–251), serious AEs (7.3;
7.0–7.7), infusion-related reactions (25.9; 25.1–26.6), and infections
(76.2; 74.9–77.4) were similar to those within the controlled treatment
period of the phase 3 trials. Rates of the most common serious AEs,
including serious infections (2.01; 1.81–2.23) and malignancies (0.46;
0.37–0.57), were consistent with the ranges reported in epidemiologic
data. Conclusion: Continuous administration of OCR for up to 7 years in
clinical trials, as well as its broader use for more than 3 years in the
real-world setting, are associated with a favorable and manageable safety
profile, without emerging safety concerns in a heterogeneous MS
population. Classification of Evidence: This analysis provides Class III
evidence that long-term, continuous treatment with OCR has a consistent
and favorable safety profile in patients with RMS and PPMS. This study is
rated Class III because of the use of OLE data and historical controls.

研究目标：报告奥瑞珠单抗（ocrelizumab, OCR）在复发型多发性硬化（relapsing multiple sclerosis, RMS）与原发进展型多发性硬化（primary progressive multiple sclerosis, PPMS）患者中长达7年的安全性，纳入研究的患者来自临床试验队列或真实世界上市后用药场景。
研究方法：安全性分析基于所有接受OCR治疗患者的整合临床与实验室数据，涉及11项临床试验，包括2期、3期试验的对照治疗期与开放标签扩展（open-label extension, OLE）阶段，以及3b期试验VELOCE、CHORDS、CASTING、OBOE、ENSEMBLE、CONSONANCE与LIBERTO。针对特定不良事件（adverse events, AEs），本研究补充使用了额外的上市后数据。严重感染与恶性肿瘤的发生率通过多个人群流行病学数据源进行背景参照校正。
研究结果：截至数据截止日期（2020年1月），共有5680例多发性硬化（multiple sclerosis, MS）患者接受OCR治疗，累计暴露时长为18218患者年（patient years, PY）。每100患者年的不良事件发生率（95%置信区间）为248（246~251），严重不良事件为7.3（7.0~7.7），输液相关反应为25.9（25.1~26.6），感染为76.2（74.9~77.4），上述发生率与3期试验对照治疗阶段的水平相近。最常见的严重不良事件发生率，包括严重感染（2.01；1.81~2.23）与恶性肿瘤（0.46；0.37~0.57），与流行病学数据报道的参考范围一致。
研究结论：在临床试验中长达7年的持续OCR给药，以及真实世界场景中超过3年的更广泛临床应用，均与良好且可控的安全性特征相关，在异质性多发性硬化人群中未出现新的安全性隐患。
证据分类：本分析提供III类证据，表明OCR长期持续治疗在RMS与PPMS患者中具有一致且良好的安全性特征。本研究被评为III类证据，原因在于使用了开放标签扩展数据与历史对照。