BACKGROUND: Satralizumab, a humanised monoclonal antibody targeting the 
interleukin-6 receptor, reduced the risk of relapse in patients with 
neuromyelitis optica spectrum disorder (NMOSD) when added to immunosuppressant 
therapy. This study assessed the safety and efficacy of satralizumab monotherapy 
in patients with the disorder.
METHODS: In this phase 3, double-blind, placebo-controlled, parallel-group 
trial, we enrolled adults aged 18-74 years with aquaporin-4 antibody 
seropositive or seronegative NMOSD at 44 investigational sites in 13 countries. 
Eligible participants had experienced at least one documented NMOSD attack or 
relapse in the past 12 months and had a score of 6·5 or less on the Expanded 
Disability Status Scale. Exclusion criteria included clinical relapse 30 days or 
fewer before baseline. Participants were randomly assigned (2:1) to receive 
satralizumab 120 mg or visually matched placebo subcutaneously at weeks 0, 2, 4, 
and every 4 weeks thereafter. Taking immunosuppressants concomitantly was 
prohibited. The primary endpoint was time to the first protocol-defined relapse, 
based on the intention-to-treat population and analysed with stratification for 
two randomisation factors (previous therapy for prevention of attacks and nature 
of the most recent attack). Safety was assessed in all participants who received 
at least one dose of satralizumab or placebo. The double-blind phase was due to 
last until 44 protocol-defined relapses occurred or 1·5 years after random 
assignment of the last patient enrolled, whichever occurred first; participants 
could enter an open-label phase after the occurrence of a protocol-defined 
relapse or at the end of the double-blind phase. The study is registered with 
ClinicalTrials.gov, NCT02073279.
FINDINGS: 95 (57%) of 168 screened participants were randomly assigned to 
treatment (63 to satralizumab; 32 to placebo) between Aug 5, 2014, and April 2, 
2017. Protocol-defined relapses occurred in 19 (30%) patients receiving 
satralizumab and 16 (50%) receiving placebo (hazard ratio 0·45, 95% CI 
0·23-0·89; p=0·018). 473·9 adverse events per 100 patient-years occurred in the 
satralizumab group, as did 495·2 per 100 patient-years in the placebo group; the 
incidence of serious adverse events and adverse events leading to withdrawal was 
similar between groups.
INTERPRETATION: Satralizumab monotherapy reduced the rate of NMOSD relapse 
compared with placebo in the overall trial population, with a favourable safety 
profile. The patient population included a ratio of aquaporin-4 antibody 
seropositive and seronegative patients that was reflective of clinical practice. 
Satralizumab has the potential to become a valuable treatment option for 
patients with NMOSD.
FUNDING: Chugai Pharmaceutical (Roche).