Real-world safety of satralizumab in neuromyelitis optica spectrum disorder: a FAERS-based risk stratification study

Satralizumab, an interleukin-6 receptor monoclonal antibody, is an established therapy for neuromyelitis optica spectrum disorder (NMOSD). While randomized trials have demonstrated their efficacy and short-term safety, real-world data characterizing report-level associations and severe adverse outcomes remain limited.

We performed a retrospective pharmacovigilance study using the U.S. FDA Adverse Event Reporting System (FAERS) from Q1 2004 to Q3 2025. Disproportionality analyses (reporting odds ratios [RORs], information components [ICs]), subgroup analyses, co-medication analysis, time-to-onset evaluation, and multivariable logistic regression for most severe outcomes (death/life-threatening events) were conducted.

Among 1174 satralizumab-related reports, infections were the most prominent signals, with key signals including atypical mycobacterial infection (ROR 109.24, 95% CI 51.92-229.82; IC 6.76, IC025 1.88), pneumonia pneumococcal (ROR 41.51, 95% CI 13.36-128.94; IC 5.37, IC025 0.45), and pyelonephritis (ROR 40.80, 95% CI 25.32-65.75; IC 5.34, IC025 2.98). Forty unlabeled events (e.g., lymphocyte count decrease [ROR 18.52, 95% CI 11.33-30.27]) were identified. Concomitant corticosteroid use was associated with increased reporting of infectious and hepatic adverse events. Among 827 reports with complete demographic data, 72 were classified as most severe. Factors associated with severe outcome reports included age ≥ 65 years (adjusted odds ratio [OR] 3.85, 95% CI 2.22-6.69), male sex (adjusted OR 2.23, 95% CI 1.20-4.15), and septic shock (adjusted OR 7.88, 95% CI 2.48-25.09). Median time to onset was 97 days (interquartile range 15-291 days), with early and late peaks.

This real-world study highlights clinically relevant safety signals of satralizumab in NMOSD, identifies vulnerable patient subgroups, and supports risk-adapted monitoring strategies in neurological practice.