BACKGROUND: No approved therapies exist for neuromyelitis optica spectrum 
disorder (NMOSD), a rare, relapsing, autoimmune, inflammatory disease of the CNS 
that causes blindness and paralysis. We aimed to assess the efficacy and safety 
of inebilizumab, an anti-CD19, B cell-depleting antibody, in reducing the risk 
of attacks and disability in NMOSD.
METHODS: We did a multicentre, double-blind, randomised placebo-controlled phase 
2/3 study at 99 outpatient specialty clinics or hospitals in 25 countries. 
Eligible participants were adults (≥18 years old) with a diagnosis of NMOSD, an 
Expanded Disability Status Scale score of 8·0 or less, and a history of at least 
one attack requiring rescue therapy in the year before screening or at least two 
attacks requiring rescue therapy in the 2 years before screening. Participants 
were randomly allocated (3:1) to 300 mg intravenous inebilizumab or placebo with 
a central interactive voice response system or interactive web response system 
and permuted block randomisation. Inebilizumab or placebo was administered on 
days 1 and 15. Participants, investigators, and all clinical staff were masked 
to the treatments, and inebilizumab and placebo were indistinguishable in 
appearance. The primary endpoint was time to onset of an NMOSD attack, as 
determined by the adjudication committee. Efficacy endpoints were assessed in 
all randomly allocated patients who received at least one dose of study 
intervention, and safety endpoints were assessed in the as-treated population. 
The study is registered with ClinicalTrials.gov, number NCT02200770.
FINDINGS: Between Jan 6, 2015, and Sept 24, 2018, 230 participants were randomly 
assigned to treatment and dosed, with 174 participants receiving inebilizumab 
and 56 receiving placebo. The randomised controlled period was stopped before 
complete enrolment, as recommended by the independent data-monitoring committee, 
because of a clear demonstration of efficacy. 21 (12%) of 174 participants 
receiving inebilizumab had an attack versus 22 (39%) of 56 participants 
receiving placebo (hazard ratio 0·272 [95% CI 0·150-0·496]; p<0·0001). Adverse 
events occurred in 125 (72%) of 174 participants receiving inebilizumab and 41 
(73%) of 56 participants receiving placebo. Serious adverse events occurred in 
eight (5%) of 174 participants receiving inebilizumab and five (9%) of 56 
participants receiving placebo.
INTERPRETATION: Compared with placebo, inebilizumab reduced the risk of an NMOSD 
attack. Inebilizumab has potential application as an evidence-based treatment 
for patients with NMOSD.
FUNDING: MedImmune and Viela Bio.