COVID Vaccine Response Varies With MS Treatment Type

New evidence continues to emerge about how multiple sclerosis (MS) disease-modifying treatments (DMTs) may affect COVID-19 vaccine response.

In a late-breaking presentation at the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) Congress, Joseph Sabatino, Jr., MD, PhD, of the University of California San Francisco (UCSF), showed that two of six DMT types had a significant effect on vaccine-induced immunity to SARS-CoV-2.

Antibody responses were quantitatively normal in MS patients on glatiramer acetate (Copaxone), dimethyl fumarate (Tecfidera), and natalizumab (Tysabri), but were reduced in patients either on sphingosine-1-phosphate (S1P) receptor modulators or on anti-CD20 therapies like ocrelizumab (Ocrevus) and rituximab (Rituxan), Sabatino said.

MS patients on S1P receptor modulators had impaired vaccine-specific CD4 T cell responses, while patients on anti-CD20 therapies had intact vaccine-induced CD4 and CD8 T cell responses. Detectable CD19 B cells and shorter duration of treatment were associated with improved antibody responses in anti-CD20 patients.

The findings also were posted on the preprint server medRxiv. “As far as I’m aware, our study was the first to report that cumulative duration of anti-CD20 therapy is associated with reduced vaccine-induced antibody responses,” Sabatino told MedPage Today.

“This research is important in helping us navigate treatment and vaccine decisions real-time with our patients,” noted co-author Riley Bove, MD, also of UCSF. “We are working very hard to understand the effects of newer agents such as ofatumumab (Kesimpta), which were approved during the pandemic.”

In a scientific session at ECTRIMS, Mihir Kakara, MD, of the University of Pennsylvania in Philadelphia, also presented research about immune responses in MS patients on anti-CD20 DMTs. The findings, recently published in Nature Medicine, showed anti-CD20 drugs significantly reduced spike-specific and receptor-binding domain-specific antibody and memory B cell responses in most patients after either Pfizer-BioNTech (Comirnaty) or Moderna mRNA vaccination. The effect was ameliorated with longer durations from the last anti-CD20 treatment.

All MS patients on anti-CD20 DMTs generated antigen-specific CD4 and CD8 T cell responses after vaccination, Kakara reported.

“Vaccinations — mRNA vaccines in our case — induce robust cellular responses despite attenuated antibody responses in B-cell depleted individuals, which means that if they are infected, they may be able to clear the virus well and possibly have reduced COVID-19 severity,” Kakara told MedPage Today.

“But for better antibody responses, delaying B-cell depletion treatment as long and safely as possible from last treatment to administer vaccine and waiting for at least 4 weeks following vaccination for next B-cell depletion treatment is suggested,” he added.

The findings are important and extend earlier work about COVID vaccine effectiveness in MS patients, noted John Corboy, MD, of the University of Colorado in Denver, who wasn’t involved with either study.

“It’s been shown that if you’re infected with COVID while you’re on an anti-CD20 drug, you may have a worse outcome,” Corboy told MedPage Today. “So, a big question is whether vaccination will adequately protect you.”

While studies involving laboratory markers of immunity are valuable, “they don’t tell us what the actual clinical ramifications are,” Corboy said.

Sabatino’s study involved 80 participants: 13 healthy controls, nine MS patients on no treatment, five patients treated with glatiramer acetate, five with dimethyl fumarate, six with natalizumab, seven with any S1P receptor modulator, and 35 with an anti-CD20 drug, including 13 on rituximab and 22 on ocrelizumab. Baseline samples were collected an average of 7 days before SARS-CoV-2 vaccination. Post-vaccine samples were collected an average of 2 weeks after the second shot for mRNA COVID-19 vaccines or 4 weeks after the Johnson & Johnson adenoviral vaccine was administered.

In Kakara’s study, 20 MS patients on anti-CD20 treatment and 10 healthy controls were assessed at the time of their first mRNA vaccine dose and 10-12 days later, then at the time of their second mRNA shot, 10-12 days after that, and 25-30 days after the dose. “It will be important to study how cell-based responses relate to protection, complications, and the risk of infecting others,” Kakara said.