The Effect of MS Treatments on SARS-CoV-2 Vaccines and the Humoral Response

Researchers determined the impact of other disease-modifying treatments in multiple sclerosis and the effect of delaying anti-CD20 infusion on the humoral response to COVID-19 vaccines.

Among patients with multiple sclerosis (MS), treatment with cladribine and teriflunomide was associated an appropriate humoral response to SARS-CoV-2 vaccines, while anti-CD20 therapies and sphingosine-1-phosphate (S1P) receptor modulators was associated with diminished response, according to study results published in JAMA Neurology. However, delaying anti-CD20 therapies by 3 to 6 months before vaccination may improve response.

Prior studies have shown a markedly reduced humoral response to SARS-CoV-2 vaccines in patients with MS treated with fingolimod and ocrelizumab. The objective of the current study was to determine the impact of other disease-modifying treatments and the effect of delaying anti-CD20 infusion on the humoral response to the vaccines.

The prospective observational cohort study included 120 (mean age, 55 years; 61.7% women) patients with MS from the Neurocenter of Southern Switzerland, including 58 patients treated with anti-CD20 therapies, 24 patients on teriflunomide, 15 patients receiving cladribine, 9 patients treated with sphingosine-1-phosphate receptor (S1P) modulators and 14 patients receiving no therapy for MS.

All participants received 2 SARS-CoV-2 messenger RNA vaccine doses and had serum samples collected within 2 weeks prior to first vaccine dose and 21-35 days after the second dose to determine immunoglobulin G (IgG) production following vaccination.

While all patients on teriflunomide and those in the no therapy group were found to be seropositive at the second serum sample, approximately half (48.2%) of those in the anti-CD20 group, a third (33.3%) of those in the S1P modulators group, and 7.1% in the cladribine remained seronegative at 21-35 days after the second vaccine dose.

While there were no significant differences in SARS-CoV-2 IgG between patients receiving no therapy and patients treated with teriflunomide or cladribine, treatments with anti-CD20 and S1P modulators were associated with lower SARS-CoV-2 IgG (P <.001).

The median time between last anti-CD20 infusion and first vaccine dose was 7.1 months and the data suggest there was a progressive increase in SARS-CoV-2 IgG with time since last anti-CD20 infusion. The researchers suggested that the humoral response to vaccines may be better if anti-CD20 infusions are delayed by 3 to 6 months before vaccination.

The study had several limitations, including the short follow-up, relatively small sample size, and lack of data on additional disease-modifying treatments.

“Future studies should aim at investigating antibody dynamics over time, if and how T cell–mediated responses after vaccination are influenced by DMTs, and whether these biological measures actually reflect vaccine efficacy in terms of preventing severe SARS-CoV-2 infection,” wrote the researchers.

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


Disanto G, Sacco R, Bernasconi E, et al. Association of disease-modifying treatment and anti-CD20 infusion timing with humoral response to 2 SARS-CoV-2 vaccines in patients with multiple sclerosis. JAMA Neurol. Published online September 23, 2021. doi: 10.1001/jamaneurol.2021.3609