Anti-CD20 disease modifying therapies decrease the humoral response to COVID-19 mRNA vaccination in patients with multiple sclerosis

ABSTRACT

Introduction: B-cell depleting (anti-CD20) disease modifying therapies (DMT) for multiple sclerosis (MS) may increase the risk for COVID-19 and worsen clinical outcomes. How these patients respond to mRNA vaccines is not known since immunosuppressed patients were not included in clinical trials. Objective/Aim: To explore the humoral response in MS patients on B-cell depleting therapies to mRNA vaccination against COVID-19. Methods: Immunoglobulin G antibodies to the SARS-CoV-2 spike protein receptor binding domain (RBD) and nucleocapsid protein (N) were measured in MS patients and compared to control participants 3-4 weeks after initial and 3-6 weeks after the second mRNA vaccination. Clinical responses to the vaccination were also collected and compared. Results: After the 2nd vaccine dose, 10/10 controls developed antibodies to RBD, but only 2/10 MS patients on anti-CD20 DMTs (OR 0.014, 95% CI 0.0005 - 0.3328). After the 1st vaccine dose, 6/7 controls had seroconverted while 0/6 seroconverted in the anti- CD20 treated MS patients. Two patients who had COVID-19 on rituximab did not developed antibodies to the nucleocapsid protein but seroconverted to RBD after the 1st vaccination dose. Antibody titers were significantly reduced in the MS patients (p<0.001). No differences in clinical response to the vaccine were observed. T-cell responses are being evaluated and will be presented. Conclusions: Patients with MS on anti-CD20 DMT are less likely to develop antibodies to SARS-CoV-2 RBD and had lower titers after mRNA vaccination. This highlights the importance of better understanding vaccine responsiveness with larger studies and developing better strategies for effective vaccination in MS patients on B-cell depleting therapies.