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    This phase 3 randomized controlled trial assessed the efficacy of eculizumab, a terminal complement inhibitor, for reducing relapse frequency in aquaporin-4–positive neuromyelitis optica spectrum disorder (NMOSD).

    Study design

    The PREVENT trial is a phase 3, multi-center, double-masked, placebo-controlled trial. Investigators enrolled 143 adults with aquaporin-4 (AQP4)-IgG-positive NMOSD who were randomized in a 2:1 ratio to receive either intravenous eculizumab or placebo. The primary endpoint was the time to first adjudicated relapse. 


    Adjudicated relapses occurred in 3 of 96 patients (3%) in the eculizumab group compared with 20 of 47 (43%) in the placebo group (hazard ratio 0.06; P<0.0001). The average baseline annualized relapse rate was 1.99 in the 24 months prior to enrollment. After treatment, the adjudicated annualized relapse rate in the eculizumab group was significantly lower than the placebo group (0.02 vs. 0.35; P<0.001).

    Rates of upper respiratory tract infection and headache were higher in the eculizumab group. One patient receiving both azathioprine and eculizumab died from pulmonary empyema.


    Approximately 3/4 of the patients received concomitant immunosuppressive therapy, which could have contributed to the excellent efficacy of eculizumab. However, 21 patients received eculizumab as monotherapy and none of these patients had a relapse compared to 7 of 13 (54%) in the placebo group, which suggests eculizumab monotherapy may be effective. A higher percentage of patients that received eculizumab (17%) discontinued their participation in the trial compared with placebo (6%), which may have influenced the results. Lastly, only patients with AQP4-IgG-positive NMOSD were included—it remains to be determined if eculizumab is beneficial in AQP4-IgG-seronegative NMOSD.

    Clinical significance

    This was a ground-breaking study that definitively proved the efficacy of eculizumab in preventing relapses in patients with AQP4-IgG-positive NMOSD, which will undoubtedly change the treatment landscape for this debilitating disease.