Study: Anti-CD20 Therapies, Gilenya Lower Efficacy of COVID-19 Vaccines

Certain treatments for multiple sclerosis (MS) — specifically, anti-CD20 antibody therapies and Gilenya (fingolimod) — are likely to reduce the effectiveness of vaccines for COVID-19, according to a new study.

“Highlighting groups who have mounted an inadequate vaccine response has already been helpful in guiding who should receive additional doses of the vaccine, and who may need to continue to take additional infection-prevention precautions over the winter,” Emma Tallantyre, co-author of the study and clinical senior lecturer in neurology at Cardiff University, said in a press release.

“We hope further work will allow us to individualize our management, to protect people with MS from COVID, while keeping their MS under control,” Tallantyre added.

The study, “COVID-19 Vaccine Response in People with Multiple Sclerosis,” was published in the Annals of Neurology.

Vaccines for COVID-19 work by training the body’s immune system to recognize the virus that causes the disease, allowing the body to more effectively repel the virus if it is encountered later on. Clinical trials have proven that vaccines can significantly lower the likelihood of getting seriously sick from COVID-19 in healthy people.

Over a dozen disease-modifying treatments (DMTs) are approved for MS, and they all work by reducing the activity of the immune system, which lessens the inflammation that drives MS — but could also dampen the effectiveness of vaccines.

Here, a team of scientists in the U.K. analyzed blood samples from 473 people with MS who had a COVID-19 vaccination. Specifically, 58 samples were collected before vaccination, 246 between the first and second vaccine doses, and 430 following the second vaccine dose. Most participants got either the Pfizer-BioNTech or Oxford-AstraZeneca vaccines.

Of the samples collected before vaccination, only 10.3% were seropositive — meaning that the samples had detectable levels of antibodies for the virus that causes COVID-19, indicating a previous infection. Antibodies are proteins made by the immune system that help prevent the virus from infecting cells.

Following vaccination, rates of seropositivity increased markedly: 56.9% after one dose and 65.1% after the second dose. The researchers noted that, in people who weren’t on any MS medications, antibody levels tended to be higher in those given the Pfizer-BioNTech vaccine, compared with the Oxford-AstraZeneca one.

Using statistical models, the researchers looked for treatments and other factors that were significantly associated with a risk of seronegativity (i.e., not mounting a detectable antibody-driven immune response after getting the vaccine).

Results showed that patients on Gilenya — an oral therapy that works by “trapping” immune cells in lymph nodes — were about 96% more likely to be seronegative following the full course of vaccines, compared with individuals who were not being treated.

The likelihood of seronegativity also was increased, by approximately 97%, in patients on anti-CD20 antibodies — a class of MS medications that work by killing B-cells (the immune cells mainly responsible for antibody production).

Approved anti-CD20 medicines for MS include Kesimpta (ofatumumab) and Ocrevus (ocrelizumab); another medication,  rituximab, also is sometimes used off-label in MS. Other anti-CD20 medicines are in development.

For all other therapies included in the analysis, no significant effect on vaccine efficacy was detected.

“With a cohort of almost 500 patients, we have demonstrated that both DMT type and vaccine type affect humoral [antibody-driven] immune response to the COVID-19 vaccination,” the researchers concluded.

Additional analyses found no difference in seronegativity risk based on the time between last treatment and getting vaccinated for patients on anti-CD20s or Gilenya — though the researchers noted that these analyses were likely too small to have detected statistically meaningful differences, emphasizing a need for further study.

Based on the results, “delaying commencement of fingolimod or anti-CD20 DMT should be considered in new starters, to allow time for vaccination,” the researchers wrote.

The findings also have implications for patients like Jo Welton, 38, a medical writer in South Wales who was diagnosed with MS in 2009.

“I have a scientific background so was interested in the study as soon as I heard about it. It was also important for me to know how much immunity I had as this impacts my day-to-day living. I’ve followed the guidelines about DMTs and MS right from the start, so this has meant I’ve been shielding for over 20 months,” Welton said.

Welton has been on Gilenya for nearly eight years. Despite getting two doses of the Oxford-AstraZeneca vaccine, she has been told she has reduced immunity to COVID-19. She’s currently waiting to find out if getting a booster shot improved her immunity.

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“It’s been so difficult seeing everyone getting back to some sort of normality and not feeling like I was able to. I feel vulnerable and, although it’s not deliberate, left behind,” Welton said. “Ignorance is bliss for some people, but it’s not a risk I want to take. Knowing I don’t have immunity means I can continue working remotely, socially distance, and ask friends and family to get their booster vaccine and do lateral flow tests [for COVID-19] when we meet.”

While MS patients on anti-CD20 therapies do not mount a robust antibody response after getting vaccinated, a study found that other parts of the immune system can become activated and help fight the virus. The findings were confirmed in this study, which showed that 40% of seronegative patients had a strong T-cell response against the virus.

“Further trials are essential to help us understand how best to balance the risks of potentially suspending or delaying MS treatment with the need to effectively vaccinate people with MS against COVID-19,” said Ruth Dobson, senior author of the study and clinical senior lecturer in neurology at Queen Mary University of London.