Patients With MS on Anti-CD20 Therapy Should Receive Additional COVID-19 Doses

Patients with MS who receive anti-CD20 therapy only see qualitative improvement in humoral immune responses following 2 or more COVID-19 vaccinations.

Among patients with multiple sclerosis (MS) who receive anti-CD20 therapy, humoral immune responses to COVID-19 vaccinations qualitatively improve with additional doses. These are the findings of a study published in the Multiple Sclerosis Journal.

Patients who receive anti-CD20 therapy for MS have been associated with worse COVID-19 outcomes and poorer immune responses to the COVID-19 vaccine.

To evaluate the effects of serial vaccination among anti-CD20 recipients with MS, researchers recruited patients (n=61) and healthy control individuals (n=10) between March and June 2022 for the study. Immune responses and neutralizing capacities were evaluated after the second, third, and fourth vaccine doses.

The patients with MS and control individuals were mean age, 40 (range, 20-68) and 31.5 (range, 26-44) years (P =.038) and 57% and 70% were women, respectively. Among the MS cohort, 18% had primary progressive MS, median Expanded Disability Status Scale (EDSS) scores were 2 (range, 0-7.0) points, and 63% had received 2 or more immunotherapies prior to anti-CD20.

SARS-CoV-2 antibody functionality improves after 3 or 4 vaccinations in aCD20pwMS with detectable SARS-CoV-2 antibodies.

All of the MS cohort were vaccinated twice, 57 were vaccinated 3 times, and 26 were vaccinated 4 times.

The proportion of the MS cohort with detectable SARS-CoV-2 spike subunit 1 (S1) immunoglobulin (Ig)G responses increased from 50.8% after dose 2 to 54.4% after dose 3 and 65.4% after dose 4. Conversely, all control individuals had detectable SARS-CoV-2-S1 IgG after the third dose. In addition, the levels of SARS-CoV-2-S1 IgG among control individuals after the third dose (median, 9.0 optical density [OD] ratio) were higher than patients after the third (median, 1.2 OD ratio; P <.001) and fourth (median, 2.4 OD ratio; P <.001) doses.

Among the patients who did not have detectable SARS-CoV-2-S1 IgG after dose 2, 22.2% had antibodies after the third dose; whereas, among those with SARS-CoV-2-S1 IgG after dose 2, 29.4% lost antibody responses after the third dose.

In SARS-CoV-2 neutralization tests using the Omicron variant, none of the 10 patients evaluated had neutralization capacity after dose 2, 30% had neutralization capacity after dose 3, and 60% after dose 4; whereas, most control individuals (70%) had neutralizing capacity after the third vaccine dose.

The patients with MS had similar SARS-CoV-2-specific T-cell responses after 2 (96%), 3 (96.1%), and 4 (92.3%) vaccine doses compared with control individuals after 3 doses (100%).

The study limitations included the small sample sizes and the lack of B-cell count data.

The researchers concluded, “[W]e show that humoral responses to SARS-CoV-2 remain quantitatively impaired in aCD20pwMS [patients with MS who received anti-CD20 therapy] after 3 or 4 vaccinations. Still, ~20% of patients who did not develop antibodies after 2 vaccinations benefited from a third vaccination by developing SARS-CoV-2 antibodies. […] These results support current recommendations for additional booster vaccinations in aCD20pwMS.”

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

This article originally appeared on Neurology Advisor


Otto C, Schwarz T, Jeworowski LM, et al. Humoral immune responses remain quantitatively impaired but improve qualitatively in anti-CD20-treated patients with multiple sclerosis after 3 or 4 COVID-19 vaccinations. Mult Scler. 2023;13524585231161253. doi:10.1177/13524585231161253