Bennett Jeffrey L, Fujihara Kazuo, Saiz Albert, Traboulsee Anthony L, Greenberg Benjamin M, Weinshenker Brian G, Patti Francesco, Kleiter Ingo, Palace Jacqueline, De Seze Jerome, Evans Rachael, Blondeau Kathleen, Klingelschmitt Gaëlle, Vodopivec Ivana, Rahim Masouda, Yamamura Takashi
Departments of Neurology and Ophthalmology, University of Colorado School of Medicine, Aurora, CO.
Department of Multiple Sclerosis Therapeutics, Fukushima Medical University School of Medicine, Japan.
Neurol Neuroimmunol Neuroinflamm. 2025 Sep;12(5):e200450. doi: 10.1212/NXI.0000000000200450. Epub 2025 Jul 31.
Satralizumab (SAT), an interleukin-6 receptor inhibitor, reduced the risk of protocol-defined relapse (PDR) vs placebo (PBO) with a favorable safety profile in patients with neuromyelitis optica spectrum disorder (NMOSD) in 2 pivotal phase 3 trials, SAkuraSky and SAkuraStar. We evaluated the long-term safety and efficacy of SAT in patients with NMOSD in the single-arm, open-label, rollover study SAkuraMoon.
Patients who completed the double-blind periods (DBPs) and open-label extensions (OLEs) of SAkuraSky and SAkuraStar were enrolled in SAkuraMoon, where they continued receiving subcutaneous SAT 120 mg 4 times a week (Q4W) ± immunosuppressive therapy. Safety analyses included all patients who received ≥1 dose of SAT in the overall SAT treatment (OST) period. The rates of adverse events (AEs) and infections per 100 patient-years (PYs) in the OST vs the DBPs were compared. Efficacy analyses were performed in the aquaporin-4 immunoglobulin-G-seropositive (AQP4-IgG+) population. Annualized investigator-assessed PDR rate (i.e., annualized relapse rate, ARR), time to first investigator-reported PDR (iPDR), severe iPDR (increase of ≥2 points in the Expanded Disability Status Scale [EDSS] score), and sustained EDSS score worsening were reported. The data cutoff date of these analyses was May 28, 2024.
Overall, 166 patients with NMOSD were included in the analysis. The median (range) SAT exposure in the OST period was 6.9 years (0-10). Rates of AEs and serious AEs (95% CI) in the OST period (AEs: 299.4 (288.8-310.2)/100 PYs; serious AEs: 8.1 (6.4-10.0)/100 PYs) were lower compared with the DBP. Rates of infections (87.5 [81.9-93.5]/100 PYs) and serious infections (2.4 [1.5-3.5]/100 PYs) in the OST period were comparable with those of the DBP and did not increase over time. No fatalities occurred. In the AQP4-IgG+ population (n = 111), the overall adjusted ARR (95% CI) was 0.07 (0.05-0.10). At Week 456 (8.8 years), 67% (56%-76%), 89% (80%-94%), and 82% (72%-89%) of SAT-treated patients were free from iPDR, severe iPDR, and sustained EDSS score worsening, respectively.
The safety and efficacy of SAT (±IST) is sustained with long-term treatment, supporting SAT as an effective maintenance therapy option for patients with AQP4-IgG+ NMOSD.
ClinicalTrials.gov registration numbers: NCT02028884 (SAkuraSky), NCT02073279 (SAkuraStar), and NCT04660539 (SAkuraMoon); EudraCT: 2020-003413-35 (SAkuraMoon).
This study provides Class IV evidence that SAT is safe and effective in patients with NMOSD.
在两项关键的3期试验SAkuraSky和SAkuraStar中，白细胞介素 - 6受体抑制剂萨特利珠单抗（SAT）与安慰剂相比，降低了视神经脊髓炎谱系障碍（NMOSD）患者符合方案定义的复发（PDR）风险，且安全性良好。我们在单臂、开放标签的延长期研究SAkuraMoon中评估了SAT对NMOSD患者的长期安全性和疗效。
完成SAkuraSky和SAkuraStar双盲期（DBP）和开放标签延长期（OLE）的患者纳入SAkuraMoon，继续接受皮下注射SAT 120 mg，每周4次（Q4W）±免疫抑制治疗。安全性分析包括在总体SAT治疗（OST）期接受≥1剂SAT的所有患者。比较了OST期与DBP期每100患者年（PYs）的不良事件（AE）和感染发生率。在水通道蛋白4免疫球蛋白G血清阳性（AQP4-IgG+）人群中进行疗效分析。报告了研究者评估的年化PDR率（即年化复发率，ARR）、首次研究者报告的PDR（iPDR）时间、严重iPDR（扩展残疾状态量表[EDSS]评分增加≥2分）和持续的EDSS评分恶化情况。这些分析的数据截止日期为2024年5月28日。
总体而言，166例NMOSD患者纳入分析。OST期SAT的中位（范围）暴露时间为6.9年（0 - 10年）。与DBP期相比，OST期AE和严重AE的发生率（95%CI）较低（AE：299.4（288.8 - 310.2）/100 PYs；严重AE：8.1（6.4 - 10.0）/100 PYs）。OST期感染发生率（87.5 [81.9 - 93.5]/100 PYs）和严重感染发生率（2.4 [1.5 - 3.5]/100 PYs）与DBP期相当，且未随时间增加。无死亡病例。在AQP4-IgG+人群（n = 111）中，总体调整后的ARR（95%CI）为0.07（0.05 - 0.10）。在第456周（8.8年）时，接受SAT治疗的患者中，分别有67%（56% - 76%）、89%（80% - 94%）和82%（72% - 89%）无iPDR、严重iPDR和持续的EDSS评分恶化。
长期治疗时，SAT（±免疫抑制治疗）的安全性和疗效得以维持，支持SAT作为AQP4-IgG+ NMOSD患者有效的维持治疗选择。
ClinicalTrials.gov注册号：NCT02028884（SAkuraSky）、NCT02073279（SAkuraStar）和NCT04660539（SAkuraMoon）；EudraCT：2020 - 003413 - 35（SAkuraMoon）。
本研究提供了IV级证据，表明SAT对NMOSD患者安全有效。
