Eculizumab Significantly Reduces Relapse Risk in Neuromyelitis Optica Spectrum Disorder


The treatment was efficacious in patients with AQP4-IgG-positive NMOSD, which accounts for nearly three-quarters of the population with the disorder, for which there is currently no approved treatment.

Sean J. Pittock, MD

Sean J. Pittock, MD

Treatment with eculizumab (Soliris, Alexion Pharmaceuticals) significantly reduces the risk for relapse among patients with AQP4-IgG-positive neuromyelitis optica spectrum disorder (NMOSD), according to results of the phase 3 PREVENT trial presented at the 2019 American Academy of Neurology Annual Meeting, May 4-10, 2019 in Philadelphia.

The results—which were simultaneously published in the New England Journal of Medicine1—are significant, as nearly three-quarters of the population with NMOSD have anti-AQP4 auto-antibodies, and there are currently no approved treatments.

“For decades, we have been hoping for a therapy that can prevent relapse and subsequent accumulation of disability by addressing a critical underlying cause of the disease,” said Michael Levy, MD, PhD, associate professor and director of the Neuromyelitis Optica Clinic at Johns Hopkins University, in a statement.2 “The substantial effect of Soliris® seen in this groundbreaking randomized, controlled study in NMOSD could potentially become a turning point for patients and their families who live in constant fear of relapse.”

The randomized, double-blind, placebo-controlled trial included 143 adults (91% women) with AQP4-IgG-positive NMOSD who were randomly assigned to receive either intravenous eculizumab (900 mg weekly for 4 weeks, followed by 1200 mg every 2 weeks) or matched placebo. Baseline annualized relapse rate for the previous 24 months was 1.99±0.94, and median scores on the Expanded Disability Status Scale (EDSS), modified Rankin scale, and Hauser Ambulation Index showed moderate to severe disability.

Patients were required to have a history of at least 2 relapses in the previous 12 months or 3 relapses in the previous 24 months, and a score of £7 in the EDSS. Those who were receiving immunosuppressive therapies for relapse prevention were allowed to continue pending stable dose regimens. Patients who were recently treated with mitoxantrone, rituximab, or intravenous immune globulin were excluded, as were patients who received doses of prednisone or other glucocorticoids greater than 20 mg per day at screening.

The primary end point was time to first adjudicated relapse. Secondary end points included adjudicated annualized relapse rate, changes in EDSS from baseline, modified Rankin scale, Hauser Ambulation Index, EQ-5D-3L visual analog scale, and EQ-5D-3L summary index.

Ultimately, 96 patients were randomly assigned to receive eculizumab and 47 received placebo. In total, 46 patients had previously received rituximab, while 34 did not receive any concomitant immunosuppressive therapy.

The primary end point of adjudicated relapse occurred in 3 of 96 patients (3%) in the eculizumab group compared with 20 of 47 patients (43%) in the placebo group (hazard ratio 0.06; 95% CI, 0.02-0.20; P <.001). The median time to first relapse was not reached in the treatment group, but occurred at 103 weeks in the placebo group; most relapses were of myelitis.

In a subgroup analysis of patients not receiving immunosuppressive therapy, no patients in the eculizumab group experienced adjudicated relapse (0/21) compared with 54% of patients (7/13) in the placebo group.

A lower annualized relapse rate was noted for the eculizumab group compared with placebo (0.02 vs 0.35, respectively; P <.001). Notably, changes in EDSS score between groups was not significant.

Adverse event rates were 745 per 100 patient-years in the treatment group compared with 1127 per 100 patient-years in the placebo group. The investigators recorded higher rates of upper respiratory tract infection and headache in the treatment group compared with placebo. Overall, adverse events deemed related to a trial regimen were 212 and 164 per 100 patient-years, respectively. The rate of serious adverse events was 27 per 100 patient-years in the treatment group compared with 55 per 100 patient-years in the placebo group, not accounting for relapses.

The investigators called out the study’s inclusion of only patients with AQP4-IgG-positive NMOSD as a limitation, as the results cannot be applied with confidence to patients without these antibodies. In addition, the short trial timeline and no observed between-group difference in change from baseline in EDSS score failed to allow investigators to infer outcomes related to disability and overall quality of life.

Future studies should focus on differences in measures of disability progression and long-term effects of eculizumab in patients with NMOSD, the investigators concluded.


1. Pittock SJ, Berthele A, Fujihara K, et al. Eculizumab in aquaporin-4-positive neuromyelitis optica spectrum disorder. N Engl J Med. Published online May 3, 2019. doi: 10.1056/NEJMoa1900866

2. Alexion Announces Successful Phase 3 PREVENT Study Of Soliris® (Eculizumab) In Patients With Neuromyelitis Optica Spectrum Disorder (NMOSD) [news release]. Boston, MA: Alexion Pharmaceuticals. September 24, 2018. Accessed May 1, 2019.

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