More Evidence That Some MS Drugs May Diminish SARS-CoV-2 Vaccine Response

By Megan Brooks

September 29, 2021

NEW YORK (Reuters Health) - A Swiss study has found an appropriate humoral response against SARS-CoV-2 at one month after vaccination in multiple sclerosis (MS) patients taking cladribine or teriflunomide, but a diminished or absent response in peers treated with anti-CD20 therapies or S1P modulators.

Studies have shown the mRNA vaccines against SARS-CoV-2 are safe in MS patients, but the humoral response to the vaccine was markedly reduced in patients treated with the anti-CD20 agent fingolimod or the S1P modulator ocrelizumab.

The Swiss team tried to replicate these findings, test other disease-modifying treatments (DMTs) and investigate whether delaying anti-CD20 infusions can enhance IgG production following vaccination.

Among 120 MS patients who received two doses of the Moderna or Pfizer-BioNTech COVID vaccines, 58 were on anti-CD20 therapy (ocrelizumab, rituximab or ofatumumab), nine were on a S1P modulator (fingolimod or ozanimod), 15 were on cladribine and 24 were on teriflunomide. The remaining 14 were not on any MS therapy.

The percentage of patients remaining seronegative 21 to 35 days after the second dose of vaccine was 48% in the anti-CD20 group, 33% in the S1P modulators group, 7% in the cladribine group, 0% in the teriflunomide group, and 0% in the no-therapy group, Dr. Claudio Gobbi of the Neurocenter of Southern Switzerland, in Lugano, and colleagues report in a research letter in JAMA Neurology.

Anti-CD20 and S1P modulators were associated with lower SARS-CoV-2 IgG (beta = -2.19, P<0.001 and beta = -1.92, P<0.001, respectively), compared with no therapy, whereas differences were not significant for teriflunomide (beta = -0.01, P=0.98) and cladribine (beta = -0.39, P=0.44).

The results also suggest that delaying anti-CD20 infusions by three to six months before COVID vaccination might increase the probability of mounting an appropriate humoral response, the researchers say.

"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," Dr. Gobbi and colleagues conclude.

In a related study in JAMA Neurology involving 112 MS patients, researchers from Israel found that those treated with ocrelizumab had a lower serology response to the Pfizer-BioNTech vaccine, compared with untreated peers and healthy controls, but generated SARS-CoV-2-specific T-cell responses comparable to healthy controls.

"Given the potential role of T cells in protection from severe disease, this is reassuring and will help physicians develop consensus guidelines regarding MS treatment in the era of the COVID-19 pandemic," write Dr. Adi Vaknin-Dembinsky with Hadassah Medical Center in Jerusalem, and colleagues.

"We think that the effective generation of a T cell response and the emerging role of T cells in protection from severe COVID-19 highlight the importance of vaccination in ocrelizumab patients, as a T cell response is expected and may confer protection from possible severe infection, even in the absence of antibody response," the authors said in a joint email to Reuters Health.

"Several publications including ours, have described decreased vaccine specific serology response in patients treated with B cell depletion therapies. In our study, only 40% of the patients treated with B cell depleting therapy had positive serology response, and when comparing to healthy controls and untreated MS patients the mean levels of antibody titer were lower in the ocrelizumab treated MS patients with positive association to time from last treatment," the researchers said.

"Although a continuous effect was not observed over time, patients that received the last ocrelizumab dose 5 or more months before vaccination had a significantly increased likelihood to have a positive serologic response than the rest of the ocrelizumab-treated study cohort," they added.

The Swiss study did not have commercial funding, whereas the Israeli research was partially supported by F. Hoffmann-La Roche Ltd, which markets ocrelizumab.

SOURCE: and JAMA Neurology, online September 23, 2021.