Yamamura Takashi, Weinshenker Brian, Yeaman Michael R, De Seze Jerome, Patti Francesco, Lobo Patricia, von Büdingen H-Christian, Kou Xiujing, Weber Kristina, Greenberg Benjamin
National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4 Chome-1-1 Ogawahigashicho, Kodaira, Tokyo 187-8551, Japan.
Mayo Clinic, 200 1st St SW, Rochester, MN 55905, USA.
Mult Scler Relat Disord. 2022 Oct;66:104025. doi: 10.1016/j.msard.2022.104025. Epub 2022 Jul 5.
This analysis evaluated long-term safety findings from the SAkuraSky and SAkuraStar studies with satralizumab in patients with neuromyelitis optica spectrum disorder (NMOSD).
SAkuraSky (satralizumab in combination with baseline immunosuppressive therapy; IST) and SAkuraStar (satralizumab monotherapy) are international, multicenter, randomized, placebo-controlled, phase 3 studies consisting of a double-blind (DB) period followed by an open-label extension (OLE). The overall satralizumab treatment (OST) period safety population comprised patients receiving ≥1 dose of satralizumab in the DB and/or OLE periods (cut-off date: 22 February 2021). Safety was evaluated in the DB and OST periods.
In the SAkuraSky DB period, patients received satralizumab (n = 41) or placebo (n = 42) in addition to stable baseline IST; 75 patients were included in the OST population. In the SAkuraStar DB period, 63 patients received satralizumab monotherapy and 32 received placebo; 91 patients were included in the OST population. Median treatment exposure in the OST period was 4.4 years (range 0.1-7.0) in SAkuraSky and 4.0 years (range 0.1-6.1) in SAkuraStar. Rates of adverse events (AEs per 100 patient-years) and serious AEs in the OST period were comparable with satralizumab and placebo in the DB periods of both studies. Similarly, overall rates of infections and serious infections were consistent between the OST and DB periods with satralizumab, with no increase in rates of infections or serious infections over time. In the OST periods, longer exposure to satralizumab was not associated with a higher risk of severe (grade ≥3) laboratory changes versus the DB periods. No deaths or anaphylactic reactions to treatment with satralizumab were reported during the OST periods of both studies.
The safety profile of satralizumab as a monotherapy or in combination with IST was maintained in the OLE, and no new safety concerns versus the DB period were observed.
ClinicalTrials.gov identifiers: NCT02028884 (SAkuraSky) and NCT02073279 (SAkuraStar).
本分析评估了SAkuraSky和SAkuraStar研究中使用萨特利珠单抗治疗视神经脊髓炎谱系障碍（NMOSD）患者的长期安全性结果。
SAkuraSky（萨特利珠单抗联合基线免疫抑制治疗；IST）和SAkuraStar（萨特利珠单抗单药治疗）是国际多中心、随机、安慰剂对照的3期研究，包括双盲（DB）期和开放标签扩展（OLE）期。总体萨特利珠单抗治疗（OST）期安全性人群包括在DB期和/或OLE期接受≥1剂萨特利珠单抗的患者（截止日期：2021年2月22日）。在DB期和OST期评估安全性。
在SAkuraSky的DB期，患者在稳定的基线IST基础上接受萨特利珠单抗（n = 41）或安慰剂（n = 42）；75名患者纳入OST人群。在SAkuraStar的DB期，63名患者接受萨特利珠单抗单药治疗，32名患者接受安慰剂；91名患者纳入OST人群。SAkuraSky的OST期治疗中位暴露时间为4.4年（范围0.1 - 7.0），SAkuraStar为4.0年（范围0.1 - 6.1）。两项研究的OST期不良事件发生率（每100患者年的AE）和严重AE与DB期萨特利珠单抗和安慰剂组相当。同样，萨特利珠单抗的OST期和DB期感染及严重感染总体发生率一致，感染或严重感染发生率未随时间增加。在OST期，与DB期相比，更长时间暴露于萨特利珠单抗与严重（≥3级）实验室检查异常风险升高无关。两项研究的OST期均未报告因萨特利珠单抗治疗导致的死亡或过敏反应。
在OLE期，萨特利珠单抗单药治疗或联合IST的安全性特征得以维持，与DB期相比未观察到新的安全问题。
ClinicalTrials.gov标识符：NCT02028884（SAkuraSky）和NCT02073279（SAkuraStar）。
