AQP4-IgG 血清阳性视神经脊髓炎谱系疾病患者使用 Satralizumab 的长期疗效：SAkuraSky 和 S AkuraStar 研究结果
Long-term Efficacy of Satralizumab in AQP4-IgG-Seropositive Neuromyelitis Optica Spectrum Disorder From SAkuraSky and SAkuraStar.
机构信息
From the Ruhr University Bochum (I.K.), Bochum, Germany, and Marianne-Strauß-Klinik, Behandlungszentrum Kempfenhausen für Multiple Sklerose Kranke gGmbH, Berg, Germany; University of British Columbia (A.T.), Vancouver, Canada; John Radcliffe Hospital (J.P.), Oxford, United Kingdom; National Institute of Neuroscience (T.Y.), National Center of Neurology and Psychiatry, Tokyo, Japan; Fukushima Medical University School of Medicine (K.F.), Japan; Service of Neurology (A.S.), Hospital Clinic and Institut d'Investigació Biomèdica August Pi i Sunyer (IDIBAPS), University of Barcelona, Spain; University of Chicago Department of Neurology (A.J.), IL; ApotheCom (D.M.), London, United Kingdom; F. Hoffmann-La Roche Ltd (H.-C.B., G.K., D.S.), Basel, Switzerland; and Departments of Neurology and Ophthalmology (J.L.B.), Programs in Neuroscience and Immunology, University of Colorado School of Medicine, Aurora.
出版信息
Neurol Neuroimmunol Neuroinflamm. 2022 Dec 8;10(1). doi: 10.1212/NXI.0000000000200071. Print 2023 Jan.
BACKGROUND AND OBJECTIVES
Satralizumab, an interleukin 6 receptor inhibitor, reduced the risk of protocol-defined relapse (PDR) vs placebo in 2 independent, double-blind studies in patients with neuromyelitis optica spectrum disorder (NMOSD). We assessed the long-term efficacy of satralizumab in patients with aquaporin-4-immunoglobulin G (IgG)-seropositive (AQP4-IgG+) NMOSD.
METHODS
Following the double-blind periods of SAkuraSky (satralizumab + baseline immunosuppressive treatment [IST]) and SAkuraStar (satralizumab monotherapy), patients could enter the open-label extension (OLE, satralizumab 120 mg Q4W ± IST). This analysis included all AQP4-IgG+ patients who received ≥1 dose of satralizumab in the double-blind and/or OLE periods, from patients' first dose to the data cutoff (February 22, 2021). PDR in the OLE period was determined by the investigator without external adjudication. We evaluated time to first investigator-reported PDR (iPDR), severe iPDR (≥2 point increase in the Expanded Disability Status Scale [EDSS] score), and sustained EDSS worsening (EDSS score increase of ≥2, ≥1, or ≥0.5 points for patients with baseline scores of 0, 1-5, or ≥5.5, respectively, confirmed ≥24 weeks post-initial worsening), plus the annualized iPDR rate (ARR).
RESULTS
Forty-six of 55 AQP4-IgG+ patients (84%) in SAkuraSky and 57/64 patients in SAkuraStar (89%) continued from the double-blind periods into the OLEs. In total, 111 AQP4-IgG+ patients received ≥1 dose of satralizumab in the double-blind and/or OLE periods and were included in these analyses (SAkuraSky: 49; SAkuraStar: 62). The median (range) duration of satralizumab exposure was 4.4 (0.1-7.0) years in SAkuraSky and 4.0 (0.1-6.0) years in SAkuraStar, with a combined 440.1 patient-years of treatment. Seventy-one of 111 patients (64%) received satralizumab for ≥192 weeks (3.7 years). At this time point, 71% (SAkuraSky) and 73% (SAkuraStar) of satralizumab-treated patients were free from iPDR, 91% (SAkuraSky) and 90% (SAkuraStar) were free from severe iPDR, and 90% (SAkuraSky) and 86% (SAkuraStar) had no sustained EDSS worsening. The overall adjusted ARR (95% CI) was 0.12 (0.08-0.18) in SAkuraSky and 0.08 (0.05-0.13) in SAkuraStar and remained stable over time.
DISCUSSION
These long-term results from the OLE periods of the SAkura studies demonstrate the continued efficacy of satralizumab over more than 3.5 years of treatment. High proportions of patients remained free from relapse, severe relapse, or worsening disease, with a consistently low ARR.
TRIAL REGISTRATION INFORMATION
ClinicalTrials.gov registration numbers: NCT02028884 (SAkuraSky) and NCT02073279 (SAkuraStar).
CLASSIFICATION OF EVIDENCE
This study provides Class II evidence that satralizumab reduces the risk of relapse in patients with AQP4-IgG+ NMOSD beyond the first 96 weeks of treatment.
背景和目的
白细胞介素 6 受体抑制剂 satralizumab 在两项独立的、双盲研究中降低了视神经脊髓炎谱系障碍（NMOSD）患者的方案定义复发（PDR）风险，与安慰剂相比。我们评估了 satralizumab 在水通道蛋白 4 免疫球蛋白 G（AQP4-IgG+）NMOSD 患者中的长期疗效。
方法
在 SakuraSky（satralizumab+基线免疫抑制治疗[IST]）和 SakuraStar（satralizumab 单药治疗）的双盲期后，患者可以进入开放标签扩展（OLE，satralizumab 120mg Q4W±IST）。本分析包括在双盲期和/或 OLE 期接受了 satralizumab 至少 1 剂的所有 AQP4-IgG+患者，从患者的首次剂量到数据截止日期（2021 年 2 月 22 日）。OLE 期间的 PDR 由研究者确定，无需外部裁决。我们评估了首次研究者报告的 PDR（iPDR）、严重 iPDR（EDSS 评分增加≥2 分）和持续的 EDSS 恶化（基线评分分别为 0、1-5 或≥5.5 的患者的 EDSS 评分增加≥2、≥1 或≥0.5 分，分别确认恶化≥24 周），以及年化 iPDR 率（ARR）。
结果
在 SakuraSky 中，55 名 AQP4-IgG+患者中的 46 名（84%）和在 SakuraStar 中的 64 名患者中的 57 名（89%）从双盲期进入 OLE。共有 111 名 AQP4-IgG+患者在双盲期和/或 OLE 期接受了 satralizumab 的至少 1 剂治疗，并纳入了这些分析（SakuraSky：49；SakuraStar：62）。SakuraSky 的中位（范围）satralizumab 暴露时间为 4.4（0.1-7.0）年，SakuraStar 为 4.0（0.1-6.0）年，总治疗时间为 440.1 患者年。71 名患者（64%）接受了 satralizumab 治疗≥192 周（3.7 年）。在这个时间点，71%（SakuraSky）和 73%（SakuraStar）的 satralizumab 治疗患者无 iPDR，91%（SakuraSky）和 90%（SakuraStar）无严重 iPDR，90%（SakuraSky）和 86%（SakuraStar）无持续的 EDSS 恶化。总体调整后的 ARR（95%CI）在 SakuraSky 中为 0.12（0.08-0.18），在 SakuraStar 中为 0.08（0.05-0.13），且随时间保持稳定。
讨论
这些来自 Sakura 研究 OLE 期的长期结果表明，satralizumab 在超过 3.5 年的治疗中持续有效。高比例的患者仍然没有复发、严重复发或疾病恶化，ARR 始终较低。
临床试验注册信息
临床试验.gov 注册号：NCT02028884（SakuraSky）和 NCT02073279（SakuraStar）。
证据分类
本研究提供了 II 级证据，表明 satralizumab 降低了 AQP4-IgG+NMOSD 患者在首次治疗 96 周后复发的风险。
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