Study Finds Low Incidence of Relapses Following Meningococcal Vaccination in AQP4-Positive NMOSD

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 (Ab+) neuromyelitis optica spectrum disorder (NMOSD). The findings suggest that vaccination prior to initiating complement component 5 inhibitor therapies may be generally safe in this population, although further studies are needed to determine whether postvaccination relapses are directly attributable to vaccination or reflect the underlying relapse risk of the disease.¹

Study Design and Incidence

Sean Pittock, MD, neurologist and autoimmune neurology specialist at Mayo Clinic in Rochester, Minnesota, and colleagues conducted a retrospective analysis of meningococcal vaccination–associated relapse events using data from three sources:

• Patients screened for the phase 3 CHAMPION-NMOSD trial (NCT04201262) of ravulizumab (Ultomiris; Alexion)
• Participants randomized to treatment or placebo in the phase 3 PREVENT trial (NCT01892345) of eculizumab
• Patients enrolled in Japanese postmarketing surveillance of eculizumab therapy

The analysis included 363 patients with AQP4-Ab+ NMOSD who had available vaccination data. The primary outcome was the proportion of patients with physician-reported relapse occurring within 4 weeks of meningococcal vaccination, either before or shortly after initiation of complement inhibitor therapy. All analyses were descriptive, reporting relapse frequencies and timing relative to vaccination.

Across all datasets, relapses occurring within 4 weeks of vaccination were uncommon. The overall mean relapse incidence was 3.3%, with a range of 0.7% to 10.6% across cohorts. In the CHAMPION-NMOSD screening population, 2 of 70 patients (2.9%) experienced relapse within 4 weeks of vaccination. The study authors noted that both patients were screen failures and did not receive ravulizumab. The relapses occurred 12 and 19 days after vaccination, and neither patient was receiving corticosteroids at the time of vaccination.¹

Within the PREVENT trial population:

• 4 of 96 patients (4.2%) assigned to eculizumab experienced relapse within 4 weeks of vaccination
• 5 of 47 patients (10.6%) assigned to placebo experienced relapse in the same period

Among the eculizumab group, three relapses occurred before therapy initiation, while one occurred on the same day as the first eculizumab dose. In the Japanese postmarketing surveillance cohort, 1 of 150 patients (0.7%) experienced relapse within 4 weeks of vaccination. The singular event occurred 12 days after vaccination and was classified as transverse myelitis. Across all cohorts, the mean interval between vaccination and relapse was approximately 1.6 weeks.

Role of Corticosteroids and Clinical Context

Many patients were receiving oral corticosteroids at the time of vaccination, which may have influenced relapse risk. 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 recent years, complement inhibition has emerged as a highly effective therapeutic approach in AQP4-Ab+ NMOSD.

In previous studies, treatment with eculizumab and ravulizumab reduced relapse risk by 94.2% and 98.6%, respectively, compared with placebo. Real-world surveillance data in Japan also demonstrated a substantial reduction in relapse rates following eculizumab initiation.²

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.

Limitations and Future Directions

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. Importantly, the analysis cannot determine whether the relapses observed were causally related to vaccination or simply reflected the underlying relapse risk of NMOSD. Investigators note that future prospective studies and larger retrospective analyses are needed to further evaluate potential links between vaccination and disease activity in NMOSD.

REFERENCES
1. Pittock SJ, Nakahara J, Parks B, Allen K, Fam S. Low incidence of relapses after vaccination in anti-aquaporin-4 antibody-positive NMOSD. Ann Clin Transl Neurol. 2026. doi:10.1002/acn3.70353
2. Pittock SJ, Berthele A, Fujihara K, et al. Eculizumab in aquaporin-4–positive neuromyelitis optica spectrum disorder. N Engl J Med. 2019;381:614-625.