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www.thelancet.com/neurology Vol 19 May 2020 371 for the treatment of NMOSD, done at six hospitals in China. Azathioprine was the first therapy observed to reduce the risk of relapses in patients with NMOSD, and although all studies supporting its use are based on class 4 evidence from observational studies, azathioprine is the most widely used current therapy, partly due to the low cost and high availability. Therefore, the comparison of tocilizumab with azathioprine pro vides a realistic appraisal of IL-6 receptor blockade in NMOSD. In the trial by Zhang and colleagues, 118 patients were enrolled (87% of whom were AQP4-IgG seropositive) and randomly assigned (1:1) to intra venous tocilizumab (8 mg/kg every 4 weeks; n=59) or oral azathioprine (2–3 mg/kg per day; n=59) for up to 60 weeks. Eight (14%) of 59 patients in the tocilizumab group had relapsed compared with 28 (47%) of 59 patients in the azathioprine group (HR 0·236, 95% CI 0·107–0·518; p<0·0001), equating to a risk reduction of 76%. The participants who had the best response were those with other concurrent autoimmune diseases. The main differences between this trial of tocilizumab and the two satralizumab trials are that the tocilizumab was administered intravenously, rather than subcutaneously, the study duration was approximately 1 year, and the investigators were not masked to the treatment alloca tion. Similar to satralizumab, adverse effects with tocilizumab were mild, including asympto matic eleva tions in liver enzymes and an increased inci dence of respiratory and urinary infections, with no signi ficant differences identified between the tocilizumab and azathioprine groups. The results of these three large trials of IL-6 blockade for the prevention of relapses in patients with NMOSD demonstrate a benefit of reduced hazard of relapse of between 55% and 74%. Two additional placebo-controlled trials in patients with NMOSD were pub lished in 2019 using drugs that tar get different immunopathological mechanisms: the first was eculizumab, a C5 complement inhibitor, which reduced the risk of relapse by 94%, and the second was inebilizumab, a CD19 B-cell depleting monoclonal antibody that reduced the risk of relapse by 73%. The safety concerns regarding these approaches are all substantially outweighed by the benefit of preventing NMOSD relapses.