BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune 
disease of the central nervous system and is associated with autoantibodies to 
anti-aquaporin-4 (AQP4-IgG) in approximately two thirds of patients. 
Interleukin-6 is involved in the pathogenesis of the disorder. Satralizumab is a 
humanized monoclonal antibody targeting the interleukin-6 receptor. The efficacy 
of satralizumab added to immunosuppressant treatment in patients with NMOSD is 
unclear.
METHODS: In a phase 3, randomized, double-blind, placebo-controlled trial, we 
randomly assigned, in a 1:1 ratio, patients with NMOSD who were seropositive or 
seronegative for AQP4-IgG to receive either satralizumab, at a dose of 120 mg, 
or placebo, administered subcutaneously at weeks 0, 2, and 4 and every 4 weeks 
thereafter, added to stable immunosuppressant treatment. The primary end point 
was the first protocol-defined relapse in a time-to-event analysis. Key 
secondary end points were the change from baseline to week 24 in the 
visual-analogue scale (VAS) pain score (range, 0 to 100, with higher scores 
indicating more pain) and the Functional Assessment of Chronic Illness 
Therapy-Fatigue (FACIT-F) score (range, 0 to 52, with lower scores indicating 
more fatigue). Safety was also assessed.
RESULTS: A total of 83 patients were enrolled, with 41 assigned to the 
satralizumab group and 42 to the placebo group. The median treatment duration 
with satralizumab in the double-blind period was 107.4 weeks. Relapse occurred 
in 8 patients (20%) receiving satralizumab and in 18 (43%) receiving placebo 
(hazard ratio, 0.38; 95% confidence interval [CI], 0.16 to 0.88). Multiple 
imputation for censored data resulted in hazard ratios ranging from 0.34 to 0.44 
(with corresponding P values of 0.01 to 0.04). Among 55 AQP4-IgG-seropositive 
patients, relapse occurred in 11% of those in the satralizumab group and in 43% 
of those in the placebo group (hazard ratio, 0.21; 95% CI, 0.06 to 0.75); among 
28 AQP4-IgG-seronegative patients, relapse occurred in 36% and 43%, respectively 
(hazard ratio, 0.66; 95% CI, 0.20 to 2.24). The between-group difference in the 
change in the mean VAS pain score was 4.08 (95% CI, -8.44 to 16.61); the 
between-group difference in the change in the mean FACIT-F score was -3.10 (95% 
CI, -8.38 to 2.18). The rates of serious adverse events and infections did not 
differ between groups.
CONCLUSIONS: Among patients with NMOSD, satralizumab added to immunosuppressant 
treatment led to a lower risk of relapse than placebo but did not differ from 
placebo in its effect on pain or fatigue. (Funded by Chugai Pharmaceutical; 
ClinicalTrials.gov number, NCT02028884.).