By Jai S. Perumal, MD
Assistant Professor of Neurology, Weill Cornell Medical College; Assistant Attending Neurologist, New York-Presbyterian Hospital
SYNOPSIS: An analysis of a large group of patients with multiple sclerosis taking various disease-modifying therapies showed that the response to COVID-19 vaccination was not uniform across the therapies. Patients taking anti-CD20 therapies and fingolimod had attenuated responses to vaccines.
SOURCE: Tallantyre EC, Vickaryous N, Anderson V, et al. COVID-19 vaccine response in people with multiple sclerosis. Ann Neurol 2022;91:89-100.
Patients with multiple sclerosis usually take sustained long-term immunomodulating/immunosuppressive therapy. This has obvious implications for recovery from infections and response to vaccinations. The degree of immunosuppression and the mechanism of action of these therapies are widely variable; therefore, one could anticipate there would be differences in the ability to respond to infections and in the effectiveness of vaccination in this group of patients.
In the context of the current COVID-19 pandemic, the authors of this study sought to investigate the effect of the various disease-modifying therapies commonly used to treat multiple sclerosis on patient response to
COVID-19 vaccination.
Patients with multiple sclerosis from five centers in the United Kingdom participated in this study. Patients were approached and consented between November 2020 and June 2021. Those who agreed to participate were sent kits with instructions on how to collect capillary blood samples and given return envelopes for specimens to be mailed back to the study site. Eluted dried blood samples were used for the analysis. Two labs conducted all the antibody testing. Potential variables that could influence vaccine response (age, gender, type of vaccine, treatment duration, disease-modifying therapy, vaccine timing in relation to infusions, and lymphocyte counts) were collected and factored into the regression modeling analysis. The primary outcome was the odds ratio (OR) of seroconversion following SARS-CoV-2 vaccination. A total of 470 patients provided samples for the study. Fifty-eight samples were done prior to vaccination, 246 between the first and second doses of the vaccination, and 430 following the second dose. One hundred eighty patients had received the BNT162b2 (Pfizer-BioNTech) vaccine, 223 patients received the ChAdOx1 nCoV-19 (Oxford-AstraZeneca) vaccine, and one received the Johnson & Johnson vaccine.
Univariate analysis showed that compared to no disease-modifying therapy, use of anti-CD20 monoclonal antibodies (OR = 0.03; 95% confidence interval [CI] = 0.01-0.06; P < 0.001) and fingolimod (OR = 0.04; 95% CI = 0.01-0.02) were associated with lower seroconversion following the completed vaccination course. All other disease-modifying therapies did not demonstrate any differences from the untreated cohort.
The disease-modifying therapies included alemtuzumab or cladribine within four years, ocrelizumab within 12 months, natalizumab within eight weeks, and fingolimod, dimethyl fumarate, teriflunomide, glatiramer acetate, or beta interferons within four weeks of the first vaccination shot. Since there was a ceiling effect on the titration of humoral response, the differences in the magnitude of response could not be studied fully. Sixteen patients who did not show a humoral response to the vaccination were subsequently analyzed for T cell immunity; 40% of them had a T cell response. The T cell responders were one patient taking alemtuzumab five months earlier, one patient taking no disease-modifying therapy, one of six patients taking fingolimod, four of six patients taking ocrelizumab, and neither of the two patients taking rituximab. The authors concluded that anti-CD20 therapy and fingolimod therapy was associated most strongly with lack of seroconversion. They did not find differences between the two vaccine types in terms of response. Some of the patients who did not have a humoral response did show T cell immunity.
COMMENTARY
Given the ongoing global COVID-19 pandemic, it is imperative that we reassess disease-modifying therapies and closely evaluate risks vs. benefits when placing patients on immunosuppressive treatment. Patients with multiple sclerosis need to be on sustained disease-modifying therapy to maintain disease control. Choosing the right therapy and timing, in the case of infusions, is of paramount importance when weighing this against the ability to fight serious infections and the humoral response to vaccination. Perhaps delaying initiation or extending infusion intervals in patients already on therapies should be considered. In this study, the anti-CD20 monoclonal antibodies and fingolimod were found to have a negative association with humoral response. We should assume that this effect extends to all modulator medications similar to fingolimod. One also should carefully consider the pros and cons of induction agents, such as alemtuzumab or cladribine. The patients receiving these two therapies were included in this study if they were up to four years from their course of treatment. Several months post-dose, one would expect a much better response to vaccination when compared to the immediate aftermath of an intravenous infusion. Caution should be taken when initiating treatment with monoclonals and fingolimod. Patients who need to be taking immunosuppressive treatments that result in suboptimal humoral vaccine responses should be advised about vigilant protective measures (masking, hand hygiene, social distancing) to decrease their risk of exposure to infection.
