Assessing COVID-19 infection probabilities in response to alternate vaccine boosting frequencies for multiple-sclerosis patients undergoing disease-modifying therapy with beta-interferon, dimethyl fumarate, natalizumab, or teriflunomide

Multiple-sclerosis patients undergoing treatment with disease-modifying therapies exhibit diverse immune responses to COVID-19 vaccinations. However, guidance on how specific treatments influence infection risks and optimal vaccination schedules remains limited. This study integrates data on vaccine-induced and infection-derived antibody responses to predict cumulative probabilities of breakthrough infections in untreated multiple-sclerosis patients and those treated with interferon, dimethyl fumarate, natalizumab, or teriflunomide. Using antibody dynamics and augmented logistic regression models, we evaluated the effectiveness of different Pfizer-BioNTech BNT162b2 booster schedules. Our findings reveal that annual boosters effectively reduce infection risks for untreated multiple-sclerosis patients, lowering their cumulative risk by more than half over two years. Among treated patients, booster vaccinations generally provide protection comparable to that of untreated patients, although treatment-specific variations in immunity are evident. For patients on interferon, annual boosters yield an even greater reduction in risk. Patients treated with dimethyl fumarate or natalizumab benefit significantly from boosters, though they experience moderately higher risks compared to untreated patients. This study underscores the importance of tailored booster schedules for MS patients, taking into account disease-modifying-therapy-specific effects on immunity. Our analysis provides actionable insights for mitigating SARS-CoV-2 risks in this vulnerable population until broader long-term infection data are available. These findings aim to guide clinicians in optimizing care for multiple-sclerosis patients in the context of ongoing COVID-19 vaccination strategies. Practice PointsO_LITailor Booster Schedules: Annual COVID-19 boosters are recommended for untreated MS patients and those on interferon, dimethyl fumarate, natalizumab, or teriflunomide; Bi-annual boosters would further reduce infection risk. C_LIO_LIAddress Risks for Immunosuppressed Patients: For patients on highly immunosuppressive treatments (e.g., fingolimod, ocrelizumab, rituximab), recognize diminished vaccine efficacy and consider supplemental measures for risk mitigation. C_LIO_LIPromote Booster Adherence and Education: Encourage timely booster adherence and educate patients on the benefits of tailored vaccination schedules, while keeping in mind the potential antiviral properties of specific therapies. C_LI