Efficacy of Satralizumab As Monotherapy in Pre-Specified Subgroups of Sakurastar, a Double-Blind Placebo-Controlled Phase 3 Clinical Study in Patients with Neuromyelitis Optica Spectrum Disorder (NMOSD)

Interleukin-6 (IL-6) is a pro-inflammatory cytokine implicated in the immune pathology of neuromyelitis optica (NMO) and NMO spectrum disorder (NMOSD). Satralizumab, a humanised recycling monoclonal antibody that binds to the IL-6 receptor, reduced risk of relapse in patients with NMO or NMOSD as add-on therapy in the SAkuraSky study (NCT02028884) and monotherapy in the SAkuraStar study (NCT02073279). SAkuraStar is a randomised, double-blind, Phase 3 clinical trial comparing satralizumab monotherapy with placebo. 95 patients with NMO or NMOSD, with ≥1 documented relapse in the year prior to screening, were randomised to satralizumab (120 mg s.c.) or placebo. The primary endpoint was time to first protocol-defined relapse (PDR). Pre-specified subgroup analyses assessed treatment response by AQP4-IgG serostatus, prior therapy, and relapse history. Between-group hazard ratios (HRs) were based on Cox proportional hazards models. Overall, satralizumab reduced risk of PDR by 55% vs placebo (n=95; HR 0.45; 95% confidence interval [CI] 0.23–0.89; p=0.018). There was a 74% reduction in PDR risk with satralizumab vs placebo in AQP4-IgG-seropositive patients (n=64; HR 0.26; 95% CI 0.11–0.63). In AQP4-IgG-seronegative patients, the HR was 1.19 (n=31; 95% CI 0.30–4.78). The proportions of AQP4-IgG-seropositive patients who were relapse-free at Weeks 48 and 96 were 82.9% and 76.5% on satralizumab, and 55.4% and 41.1% on placebo, respectively. In AQP4-IgG-seronegative patients, proportions were 63.3% and 63.3% on satralizumab, and 77.8% and 77.8% on placebo, respectively. In patients previously treated with B-cell depleting therapy, the HR for PDR was 0.72 (n=12; 95% CI 0.12–4.30) with satralizumab vs placebo. In patients on prior immunosuppressant or other NMO/NMOSD therapies, this HR was 0.42 (n=83; 95% CI 0.20–0.87). Patients with >1 relapse in the year prior to screening had a HR for PDR of 0.42 with satralizumab vs placebo (n=84; 95% CI 0.21–0.85); those with one relapse during screening had no change in PDR risk (n=11; HR: 1.00, 95% CI 0.09–11.02). Satralizumab was effective in reducing risk of PDR in patients with NMO or NMOSD, particularly in AQP4-IgG-seropositive patients. The study was not powered for subgroup analyses; therefore, results should be interpreted with caution.