Long-Term Efficacy and Safety of Satralizumab in Patients With Neuromyelitis Optica Spectrum Disorder From the SAkuraMoon Open-Label Extension Study.
Bennett JL., Fujihara K., Saiz A., Traboulsee AL., Greenberg BM., Weinshenker BG., Patti F., Kleiter I., Palace J., De Seze J., Evans R., Blondeau K., Klingelschmitt G., Vodopivec I., Rahim M., Yamamura T.
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.