Abstract
BACKGROUND AND OBJECTIVES: 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. METHODS: 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. RESULTS: 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. DISCUSSION: 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. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov registration numbers: NCT02028884 (SAkuraSky), NCT02073279 (SAkuraStar), and NCT04660539 (SAkuraMoon); EudraCT: 2020-003413-35 (SAkuraMoon). CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that SAT is safe and effective in patients with NMOSD.