Vaccines and the association with relapses in patients with neuromyelitis optica spectrum disorder

A retrospective study was conducted to determine whether vaccinations were associated with an increased risk of relapse in patients with Neuromyelitis Optica Spectrum Disorder (NMOSD). Patient records were reviewed from three NMOSD centers: the Johns Hopkins NMO Clinic in Baltimore, USA, NeuroCure research Center at Charité University Hospital in Berlin, Germany, and Neuroclinica in Medellín, Colombia. All patients with comprehensive health records related to their NMOSD and who had follow-up information for at least 90 days after their most recent vaccination were included in this analysis.

In order to determine whether there was an increased risk of relapse following a vaccination, the researchers compared relapses that occurred 30, 60, and 90 days after vaccination with relapses that occurred within randomly selected dates. For the purposes of this study, relapses were defined as “a new or worsening acute neurologic symptom lasting 24 hours, associated with a change in exam localizing to the [central nervous system] CNS and not explainable by fever, infection or metabolic condition.” The NMOSD patients were divided into two groups: those who were taking preventative immunotherapy medication such as rituximab, mycophenolate mofetil, azathioprine, methotrexate, or prednisone, and those who were not on a preventative immunotherapy, which included patients who were taking glatiramer acetate and interferon beta, as these medications have been found to worsen or not be effective in NMOSD.

Ninety patients who received a total of 211 vaccinations were included in this study. The median disease course was 6.6 years, and 340 relapses had occurred during this timeframe. Intramuscular influenza was the most common vaccine received (61% of the vaccines received).

The researchers found that vaccines were not significantly associated with relapses among patients on preventive immunotherapy such as rituximab, mycophenolate mofetil, azathioprine, methotrextate, or prednisone. However, the researchers found that vaccines were significantly associated with relapses in patients who were not on preventive immunotherapy. Also, among patients on preventive immunotherapy, routine vaccinations were associated with lower annualized relapse rates.

There were 7 patients who relapsed within 30 days of a vaccination, 6 patients who relapsed 31-60 days after a vaccination, and 3 patients who relapsed 61-90 days after a vaccination, for a total amount of 16 patients experiencing relapses within 90 days after a vaccination. Five of the inflammatory attacks were at the disease onset and eleven were relapses that occurred later in the course of the disease. The highest proportion of vaccination-associated relapses were after tetanus/diphtheria vaccines, as 15% of patients receiving this vaccination relapsed within 90 days.

118 of the 211 vaccinations in this study were administered to patients who were on immunosuppressive therapy. Most (13 of the 16) patients who experienced relapses were not on immunotherapy, and one patient was on glatiramer acetate, which is not an effective treatment for NMOSD. The remaining two patients were on immunosuppressive treatment for an average duration of 47 months.

As stated above, the researchers found that routine vaccination was associated with an 81% lower risk of relapse in patients who were using preventive immunotherapy than patients who were not vaccinated after their initial disease onset. A possible explanation for this finding is that relapses can be triggered by immune system activation, and vaccinations help prevent infections that cause immune system activation, which results in fewer relapses.

The researchers suggest that individuals with NMOSD take preventive immunotherapy treatment prior to receiving any future vaccinations.

The authors of the study note several limitations to this study. For example, they did not include patients who received live attenuated vaccines, such as Japanese encephalitis and yellow fever vaccines, which have been associated with relapses in NMOSD. Additionally, few patients had received the HPV vaccine, which has been associated with relapses in case studies of NMOSD patients. The authors also had limited information and could not include data on the adjuvants that were used for each of the vaccines. Also, there were few aquaporin-4 negative patients included in the study, so additional studies should confirm these findings with aquaporin-4 negative patients. Lastly, there are inherent biases in retrospective data analyses, which could have influenced the results of this study. The study also did not look at vaccine-preventable infections, such as the flu, and their potential association with relapses. The results of the study should be understood within the context of these limitations and biases.

To address the issues with this study, the researchers suggest that there should be a comprehensive, well-controlled prospective study that investigates relapses, vaccines, and infections.

Mealy MA, Cook LJ, Pache F et al. Vaccines and the association with relapses in patients with neuromyelitis optica spectrum disorder. Mult Scler Relat Disord. 2018 Jul;23:78-82. doi: 10.1016/j.msard.2018.05.003. Epub 2018 May 7.