Low Relapse Incidence After Meningococcal Vaccination in AQP4-Positive NMOSD
In AQP4-positive NMOSD, relapse within 4 weeks of meningococcal vaccination was uncommon (3.3% overall). Findings support vaccination as a generally acceptable prerequisite before C5 inhibitor therapy, with causality still unclear.
A retrospective analysis of clinical trial and real-world datasets found a low incidence of physician-reported relapses within 4 weeks of meningococcal vaccination among patients with aquaporin-4 (AQP4)-antibody positive neuromyelitis optica spectrum disorder (NMOSD), suggesting that vaccination prior to initiating complement component 5 inhibitor therapies may be generally safe in this population.
The analysis included 363 patients with AQP4-Ab+ NMOSD who had available vaccination data from patients screened for the phase 3 CHAMPION-NMOSD trial of ravulizumab, participants randomized in the phase 3 PREVENT trial of eculizumab, and patients enrolled in Japanese postmarketing surveillance of eculizumab therapy. The primary outcome was the proportion of patients with physician-reported relapse occurring within 4 weeks of meningococcal vaccination. Across all datasets, the overall mean relapse incidence was 3.3%, with a range of 0.7% to 10.6% across cohorts.
Across cohorts, relapses within 4 weeks of vaccination were uncommon:
- In the CHAMPION-NMOSD screening population, 2 of 70 patients (2.9%) experienced relapse within 4 weeks of vaccination; both were screen failures and did not receive ravulizumab, with relapses occurring 12 and 19 days after vaccination, and neither was receiving corticosteroids.
- In the PREVENT trial, 4 of 96 patients (4.2%) assigned to eculizumab and 5 of 47 patients (10.6%) assigned to placebo experienced relapse within 4 weeks of vaccination; among the eculizumab group, three relapses occurred before therapy initiation and one on the same day as the first dose.
- In the Japanese postmarketing surveillance cohort, 1 of 150 patients (0.7%) experienced relapse within 4 weeks of vaccination, at 12 days postvaccination, classified as transverse myelitis.
Across all cohorts, the mean interval between vaccination and relapse was approximately 1.6 weeks.
Many patients were receiving oral corticosteroids at the time of vaccination; in the PREVENT trial, 58.2% of patients receiving eculizumab and 47.8% receiving placebo were on corticosteroids during vaccination. Although the number of relapse events was too small to determine statistical associations, the authors noted that concomitant corticosteroid therapy may potentially mitigate relapse risk during vaccination.
Preventing relapses remains the primary goal of NMOSD management because each attack may result in permanent neurologic disability. In previous studies, treatment with eculizumab and ravulizumab reduced relapse risk by 94.2% and 98.6%, respectively, compared with placebo. Because complement inhibition increases susceptibility to meningococcal infection, vaccination prior to therapy initiation is considered a critical safety measure. These findings provide reassurance that meningococcal vaccination appears to carry a relatively low short-term relapse risk in patients with NMOSD.
The investigators noted several limitations, including the retrospective design, lack of a control group, and reliance on physician-reported relapse events that were not formally adjudicated in all datasets. The analysis cannot determine whether the relapses observed were causally related to vaccination or simply reflected the underlying relapse risk of NMOSD.