Pretreatment Meningoccal Vaccination Rates High Among Patients With NMOSD Transitioning From Rituximab to Ravulizumab

Michael Levy, MD, PhD

(Credit: Harvard Medical School)

A recent post-hoc analysis of the CHAMPION-NMOSD trial (NCT04201262) at the 2025 Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum, held February 27 to March 1, in West Palm Beach, Florida, showed that most patients with neuromyelitis optica spectrum disorder (NMOSD) who transitioned from rituximab (Rituxan) to ravulizumab (Ultomiris; Alexion) received meningococcal vaccinations within 6 months of their last rituximab dose.¹ These findings reinforce the thought that timely vaccination may mitigate the risk of meningococcal infections in this population.

The analysis included 19 patients with NMOSD who were on rituximab and later transitioned to ravulizumab. The study primarily focused on the timing of meningococcal vaccinations, MenACWY or MenB, in relation to the last rituximab dose. All told, results showed that a majority of patients (68.4%) received their first meningococcal vaccinations in 6 months of their last rituximab dose, with most receiving both MenACWY and MenB vaccines during the same visit. Authors noted that no cases of meningococcal infection were reported following vaccination.

Presented by coauthor Michael Levy, MD, PhD, associate professor of neurology at Harvard Medical School, the study aimed to assess the timing and safety of these vaccinations, considering the immunosuppressive effects of rituximab and the need for meningococcal protection when initiating complement inhibitors like ravulizumab. The cohort consisted mostly of White (63.2%) and North American (68.4%) patients, with a predominance of women (94.7%). Lymphocyte counts were normal in most patients, which could be noteworthy given the immunosuppressive effects of rituximab. Additionally, there were no reports of NMOSD relapses or infections following vaccination, suggesting that the timing of meningococcal vaccinations may not interfere with the safety of transitioning to ravulizumab.

"There is a general concern in the NMO community when switching from rituximab to complement therapy such as eculizumab or ravulizumab, that vaccination for meningococcus would be ineffective in the absence of circulating B cells. There are previous studies showing that vaccinations in people on rituximab produce a limited antibody response but in the case of meningococcus vaccination, it’s unclear how important an antibody response is," Levy, who also serves as the research director of the Division of Neuroimmunology & Neuroinfectious Disease at Massachusetts General Hospital, told NeurologyLive^® in a recent interview.

READ MORE: Ketogenic Diet Shows Potential for Modulating Immune Response in Multiple Sclerosis

The CHAMPION-NMOSD study, a global, open-label phase 3 trial, primarily evaluated the efficacy of ravulizumab in patients with anti-aquaporin-4 antibody-positive NMOSD. Approximately one-third of the trial participants had prior exposure to rituximab, a commonly used off-label treatment for NMOSD. Given the risk of meningococcal infections in patients receiving complement inhibitors like ravulizumab, vaccination against Neisseria meningitidis (Nm) may be crucial for these individuals.

"We reviewed data from the CHAMPION trial of ravulizumab in NMO. In the trial, there were 19 people who switched from rituximab to ravulizumab, 13 of whom started ravulizumab less than 6 months after their last rituximab dose, and 18 of whom started ravulizumab within 8 months of their last rituximab dose," Levy said. "In all of these cases, B cells counts were likely suppressed and the antibody response to the first meningococcus vaccine would be limited. At the time of the second dose of the meningococcus vaccine up to 6 months later, B cell counts were likely recovering or recovered."

The post-hoc analysis specifically focused on patients who had received rituximab and subsequently started ravulizumab. All patients had received at least 1 dose of a meningococcal vaccine, MenACWY or MenB, at least 2 weeks before the initiation of ravulizumab. The analysis revealed that 68.4% of the patients were vaccinated either in 0–3 months (15.8%) or 3–6 months (52.6%) after their last dose of rituximab.

"Antibody responses to the meningococcus vaccine were not measured in the study. We also did not go back to samples and try to re-consent patients to do that. The outcome that we measured was meningococcus infection," Levy noted in the interview. "In the study of 64 total people, 2 developed meningococcus infection. Both of these infections occurred despite vaccination, but neither was vaccinated after rituximab. One of the patients who developed the infection was vaccinated to meningococcus 1.5 years prior to rituximab usage. The conclusion is that it seems that rituximab does not obviously impair vaccine responses to meningococcus."

Vaccination occurred predominantly during a single visit, with 84.2% of patients receiving both MenACWY and MenB vaccines. In total, 21% of patients received multiple doses of either vaccine. Importantly, there were no reports of meningococcal infections in patients who received their initial vaccination after their last rituximab dose. Furthermore, total lymphocyte counts remained in normal limits for most patients (92.3%), a finding that could suggest that the immunosuppressive effect of rituximab had largely resolved prior to the initiation of ravulizumab.

"The challenge is that we did not measure vaccine antibody responses in any of these patients. Based on our experience with rituximab, it is likely that rituximab is limiting the antibody response to the vaccine. However, there seems to be a sufficient cellular immune response to the vaccine that patients did not develop infections. The sample size is small and we cannot draw reliable conclusions from an analysis like this," Levy said. "First, we need to understand how vaccine antibodies correlate with efficacy. This is a study that has not yet been done. If antibody responses do correlate with efficacy, we prospectively follow these levels in people switching from rituximab to complement therapy in order to maximize their vaccine schedule and further reduce the risk of meningococcus infection."

Importantly, the timing of patient vaccinations did not result in meningococcal infections or NMOSD relapses, which may underscore the safety of this vaccination schedule. These results were consistent with the importance of vaccinating patients at risk for meningococcal infection when initiating complement inhibitor therapy like ravulizumab, without compromising patient safety.²

"This study provides a little reassurance to doctors and patients who are considering a switch from rituximab to complement therapy. It tells us that there is no obvious risk in vaccinating NMO patients on rituximab switching to complement therapy," Levy added. "I am not aware of a study that looked at potential risks and benefits of administering both MenACWY and MenB at the same visit. While the MenACWY does not contain an adjuvant, the Bexsero MenB vaccine does (aluminum based). Theoretically, there is a risk that immune overactivation from a vaccine can trigger an NMO relapse."

"It’s important that patients know that this risk of vaccine-induced relapse is theoretical and it’s something we are going to monitor in all NMO patient who take any vaccine. But at this time, we don’t have evidence that this occurs with meningococcus vaccines," Levy told to NeurologyLive.

Click here for coverage of 2025 ACTRIMS Forum.

REFERENCES
1. Bennett JL, Akpoji U, Bhattacharyya S, et al. Time to Vaccination After Rituximab Discontinuation in Patients with Anti-Aquaporin-4 Antibody-Positive Neuromyelitis Optica Spectrum Disorder: A Post-Hoc Analysis of the CHAMPION-NMOSD Trial. Presented at ACTRIMS Forum 2025; February 27 to March 1; West Palm Beach, Florida. P295.
2. Makkawi S, Salamatullah HK, Alkhiri A, et al. Role of C5 inhibitors in neuromyelitis optica spectrum disorders with seropositive anti-aquaporin-4 antibody: A systematic review and meta-analysis. Mult Scler Relat Disord. 2024;85:105524. doi:10.1016/j.msard.2024.105524