Another class of MS drugs raises concerns over COVID vaccine protection
Multiple sclerosis (MS) patients treated with cladribine (Mavenclad) or teriflunomide (Aubagio) experienced an appropriate humoral response against SARS-CoV-2 one month after vaccination, but those treated with anti- CD20 or the sphingosine-1-phosphate (S1P) receptor modulators did not, a Swiss study showed.
Out of 120 MS patients at the Neurocenter of Southern Switzerland who received the Moderna or Pfizer-BioNTech (Comirnaty) mRNA vaccine, the percentage remaining seronegative 21-35 days after the second dose was 48.2% in a group receiving anti-CD20 therapies, 33.3% in the S1P modulator group, 7.1% in the cladribine group, 0% in the teriflunomide group and 0% in a group that received no MS treatment, reported Claudio Gobbi, MD, from the Neurocenter of Southern Switzerland in Lugano, and co-authors, in a JAMA Neurology research letter.
A total of 58 patients were on anti-CD20, including 32 on ocrelizumab (Ocrevus), 25 on rituximab (Rituxan) and one on ofatumumab (Kesimpta). Nine people were on S1P modulators, including seven on fingolimod (Gilenya) and two on ozanimod (Zeposia). The cohort also included 15 MS patients on cladribine, 24 on teriflunomide and 14 without treatment. Serum samples were taken in the 2 weeks before the first dose of vaccine and on average 26 days after the second dose.
In a short related report, also published in JAMA Neurology, researchers in Israel showed that MS patients on ocrelizumab generated specific T-cell responses to SARS-CoV-2 comparable to healthy controls, but had a weaker antibody response after the Pfizer COVID-19 vaccine.
“Given the potential role of T cells in protecting against serious illness, this is reassuring and will help doctors develop consensus guidelines for treating MS in the era of the COVID-19 pandemic,” said writes Adi Vaknin-Dembinsky, MD, PhD, of Hadassah Medical Center in Jerusalem, and colleagues.
Of the 112 participants in the single-center study, 49 had MS and were treated with ocrelizumab, 23 had MS and were not treated with DMARDs, and 40 were healthy controls.
2-8 weeks after their second vaccine injection, 26 of 29 MS patients (89.7%) treated with ocrelizumab and 15 of 15 healthy controls had SARS-CoV-2 specific T cells at similar levels (mean 15.4 and 14.3 cells, respectively). A lower percentage of positive SARS-CoV-2 antibody response and lower IgG titers were observed in patients treated with ocrelizumab than in healthy controls and untreated patients.
The findings echo those recently seen in other small studies on immune responses in MS patients on anti-CD20 therapy after COVID vaccination. They also reflect data showing weaker COVID antibody responses in MS patients on anti-CD20 treatment who were infected with COVID-19.
An earlier study showed an altered humoral response to COVID-19 vaccination for MS patients on ocrelizumab and S1P receptor modulators. In addition, a preprint paper on medRxiv, not yet peer-reviewed, showed that anti-CD20 drugs and S1P receptor modulators resulted in a significant reduction in spike-specific IgG responses after COVID vaccines.
Ocrelizumab depletes circulating B cells within 2 weeks of treatment, but spares CD20 negative plasma cells, stem cells and pro-B cells, observed Vaknin-Dembinsky and co-authors.
“We found that patients vaccinated 5 months or more after the last dose had a higher likelihood of a positive serologic response,” they wrote. “The individual serological response may depend on a combination of factors.”
Vaccines timed with doses of ocrelizumab – a strategy recommended by the National Multiple Sclerosis Society – may improve antibody responses, noted Vaknin-Dembinsky and colleagues. It is not known to what extent patients who have a negative serologic response but who produce vaccine-specific T cells are protected, they added.
The Swiss study was supported by institutional funds from the Neurocenter in southern Switzerland. Researchers reported relationships with Gilead Sciences, MSD, ViiV Healthcare, AbbVie, Pfizer, Almirall, Biogen, Celgene, Merck, Novartis, Roche, Sanofi Genzyme, Teva, Lilly, and Lundbeck.
The Israeli study was partially supported by F. Hoffmann-La Roche, who developed and markets ocrelizumab. The researchers reported relationships with F. Hoffmann-La Roche, Roche, Biogen, Genzyme Sanofi, Merck, Novartis and the Israel Ministry of Health.