Third mRNA COVID-19 Vaccine Dose Safe for Patients With Multiple Sclerosis

Marton König, MD, PhD

A recently conducted cohort study found that a third dose of an mRNA COVID-19 vaccine, either BNT162b2 (Pfizer/BioNTech) or mRNA-1273 (Moderna), was safe for patients with multiple sclerosis (MS). Investigators further observed a modest increase in levels of anti-SARS-CoV-2 spike receptor-binding domain (RBD) immunoglobulin G (IgG) antibodies in patients that had reduced protective humoral immunity prior to reimmunization.¹

Investigators, led by Marton König, MD, PhD, senior house officer and researcher, department of neurology, Oslo University Hospital, in Oslo, Norway, initially invited a total of 175 patients with MS from 3 university hospitals, with 130 patients (74.2%) meeting inclusion criteria. Enrollment began March 23, 2021, with antibody testing performed before October 1, 2021; patients had a median age of 47.5 years (interquartile range, 40.6-56.0), and 74.6% were women (n = 97).

A total of 100 patients (76.9%) received rituximab (Rituxan; Genentech) and 1 patient (0.8%) received ocrelizumab (Ocrevus; Genentech), making up the combined anti-CD20 group; and 29 patients (22.3%) received fingolimod (Gilenya; Novartis). After full vaccination, mean arbitrary unit (AU) levels of anti-SARS-CoV-2 spike RBD IgG titer varied depending on the disease-modifying therapy patients were receiving, with levels at 8.9 AU (standard deviation [SD], 13.9) in the anti-CD20 group and 9.2 (SD, 12.7) in the fingolimod group. Levels increased significantly in both treatment groups following revaccination, improving to 49.4 AU (SD, 75.7) in the anti-CD20 group (P <.001) and 25.1 AU (SD, 29.6) in the fingolimod group (P = .006). 

Twenty-five of 101 patients (24.8%) patients given antibody therapy and 2 of 29 patients (6.9%) given fingolimod had assumed protective humoral immunity, defined as IgG levels greater than 70 AU, following revaccination. For patients with RBD IgG less than 70 AU, compared with those with RBD IgG greater than 70 AU, investigators found that absolute lymphocyte count—mean 1262 cells/mm3 (SD, 584) for those with less than 70 AU vs 1508 cells/mm3 (SD, 560) for those with great than 70 AU (P = .03)—was associated with development of protective humoral immunity. Also associated with protective humoral immunity was higher CD19 B-cell counts in patients receiving anti-CD20 therapy, who reported 6 cells/mm3 (SD, 17) vs 25 cells/mm3 (SD, 53; P = .03) in those not on anti-CD20 therapy. 

“The results of this cohort study showed that a third dose of the mRNA COVID-19 vaccine was safe and associated with modestly increased levels of anti–SARS-CoV-2 spike RBD IgG antibodies in patients with reduced protective humoral immunity before reimmunization. A higher absolute lymphocyte count was associated with a better antibody response and more adverse effects, and a higher proportion of patients who were treated with anti-CD20 therapy experienced a better antibody response than patients treated with fingolimod,” König et al wrote. “A 25% increase in the number of patients who experienced seroconversion after revaccination and who were treated with anti-CD20 therapy may be of clinical relevance, as these patients have an approximately 3-fold risk of developing serious COVID-19; therefore, our study results suggest that revaccination of these patients should be considered.”

There was no correlation identified between antibody responses and time from last anti-CD20 infusion to revaccination (Spearman ρ correlation coefficient, 0.70; P = .50) or the cumulative duration of treatment (Spearman ρ correlation coefficient, −0.17; P = .09). Sixty-four of 101 patients (63.4%) treated with anti-CD20 therapy experienced adverse effects (AEs), compared with 11 of 29 patients (37.9%) treated with fingolimod. The most common AEs were transient local pain and fatigue, and there were no serious AEs reported after revaccination. For patients who reported AEs, mean absolute lymphocyte count was found to be higher, at 1410 cells/mm3 (SD, 594), when compared with those who did not report AEs, who had a mean absolute level of 1183 cells/mm3 (SD, 564; P = .03). 

The study only included assessments of IgG response as a measure of presumed humoral immunity, which was noted as the primary limitation, with investigators adding that antibody levels are not fully predictive of whether a patient it protected from COVID-19 levels. Conversely, levels lower than the cutoff may also be protective and immune response may further depend on T-cell responses. 

Since the outbreak of the COVID-19 pandemic, there have been questions abound surrounding the immune response and concerns for patients with MS, though data have been published in recent months quelling those concerns. In the fall of 2021, at the 2021 Annual Meeting of the Consortium of Multiple Sclerosis Centers (CMSC), October 25-28, Amit Bar-Or, MD, FRCPC, FAAN, FANA, Melissa and Paul Anderson President’s Distinguished Professor; director, Center for Neuroinflammation and Neurotherapeutics; and chief, Multiple Sclerosis Division, department of neurology, Perelman School of Medicine, University of Pennsylvania, gave a presentation on the interaction of the vaccine with disease-modifying therapies. Following that presentation, he spoke with NeurologyLive about the need for patients to get vaccinated and offered his takeaways for the clinical community.

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REFERENCE
1. König M, Torgauten HM, Tran TT, et al. Immunogenicity and safety of a third SARS-CoV-2 vaccine dose in patient with multiple sclerosis and weak immune response after COVID-19 vaccination. JAMA Neurol. Published online January 24, 2022. doi:10.1001/jamaneurol.2021.5109