Mark Gudesblatt, MD
Previous studies exploring vaccination responses in the setting of certain disease-modifying therapies noted that B-cell–depleting agents and fingolimod were associated with poorer vaccination responses, as measured by antibody titers. Another prospective study explored mitigating strategies for people with MS treated with fingolimod and concluded that discontinuation of disease-modifying therapy improved the humoral response generated after SARS-CoV-2 vaccination ( Achiron et al ). Specifically, 20 people with MS treated with fingolimod therapy, who received the third dose of BNT162b2 (Pfizer-BioNTech) vaccine after not developing a humoral immunoglobulin (Ig) G immune response to the previous two doses, were randomly assigned to the fingolimod-continuation or fingolimod-discontinuation group. In this cohort, 80% vs. 20% of patients in the fingolimod-discontinuation vs. fingolimod-continuation group developed a positive humoral response against SARS-CoV-2 at 1 month after the third vaccine dose, with a significantly higher median G titer in the fingolimod-discontinuation vs. fingolimod-continuation group (202.3 vs. 26.4 binding antibody units/mL; P = .022). Certain B-cell–depleting agents adversely influence serum Ig levels, and other B-cell–"impacting" agents appear to not. In one study, extended ofatumumab treatment in a group of people with MS (N = 1969) for up to 3.5 years was both well tolerated and not associated with new risks. In this study, 83.8% and 9.7% of patients experienced at least one AE and one serious AE, respectively. Systemic injection-related reactions, infections, and cancers were reported in 24.8%, 54.3%, and 0.3% of patients, respectively. In most patients, the mean serum IgG and IgM levels were stable and above the lower limit of normal, and the risk for serious infections remained low, as seen with Ig deficiencies ( Hauser et al ).
Practical points for clinicians who treat MS to include in discussions with people with MS about choice of disease-modifying therapy and ongoing treatment include the safety and tolerability of vaccinations, the limited effect of vaccination on relapse in MS, the effect of specific disease-modifying therapies on vaccination responses and vaccine efficacy, and the importance of Ig levels and ongoing monitoring of Ig levels in routine care.