Two MS Meds Tied to Higher COVID Rates

Kelli Whitlock Burton

April 28, 2022

Editor's note: Find the latest COVID-19 news and guidance in Medscape's Coronavirus Resource Center.

Patients taking ocrelizumab (Ocrevus) or fingolimod (Gilenya) for treat multiple sclerosis (MS) have higher rates of COVID-19 infection and hospitalization before and after COVID vaccination, compared with those taking other treatments, a nationwide study in England found.

The study draws on a database that includes every patient with MS in England treated with a disease modifying therapy (DMT) and national data on rates of COVID infection, hospitalization, mortality, and vaccination in those patients.

It's the latest work to suggest varying levels of vaccine efficacy based on DMT use and is the first known study to offer this level of detail on the subject.

"What is obvious is that current vaccination protocols for these DMTs are not really working properly," lead investigator Afagh Garjani, MD, clinical research fellow at the University of Nottingham, United Kingdom, told Medscape Medical News.

Although the differences in infection rates and efficacy are significant in those two DMTs, the overall infection and hospitalization rates were low, Garjani notes, offering further evidence that vaccines are effective in most patients with MS.

The findings were presented at the American Academy of Neurology (AAN) 2022 Annual Meeting.

Low Mortality Rate

The prospective, longitudinal study included National Health Service data on 44,170 people with MS. The data on hospitalization came from 29,353 patients with MS who had received at least two doses of a COVID-19 vaccine.

Patients taking dimethyl fumarate, the most commonly prescribed DMT in England, had similar rates of COVID infection in January 2021 — before they were fully vaccinated — and in December 2022, after they had received at least two vaccine doses.

However, among patients taking fingolimod and ocrelizumab there were significant increases in infection rates in that same time period. The incidence rate ratio (IRR) in the fingolimod group was 0.50 (95% CI, 0.37 - 0.66) in January 2021 and rose to 0.91 (95% CI, 0.80 - 1.03) in December 2022. In the ocrelizumab group, the IRR rose from 1.01 (95% CI, 0.79 - 1.26) to 1.57 (95% CI, 1.44 - 1.72) during that timeframe.

Hospitalization rates were also higher in fully vaccinated patients with MS taking fingolimod and ocrelizumab. People taking dimethyl fumarate had a hospitalization rate of 32 (per 10,000 people) compared with a rate of 140 in patients on ocrelizumab and 94 in patients on fingolimod.

Mortality rates were low in all groups, but were slightly higher in the ocrelizumab group.

"However, the number of people who died due to COVID overall was small," Garjani noted.

Following receipt of a third COVID-19 vaccine, the only hospitalizations were in patients taking ocrelizumab (4 out of 65 infections) and fingolimod (11 out of 78 infections), with no deaths.

Potential Mechanism

Researchers suspect the reason for varying COVID-19 infection rates and vaccine efficacy among DMTs is related to their mode of action.

"With MS, the immune system attacks the central nervous system and the aim of these treatments is to modulate or suppress the immune system," Garjani said. "Some of these medications are immune suppressants and therefore, in addition to preventing MS, might also put people at increased risk of infection from COVID or other diseases."

Ocrelizumab and fingolimod have different modes of action, but both act as immunosuppressants.

Study data on beta-interferon offered an interesting twist. Patients taking that medication had far lower infection rates compared with other DMTs and to the general population, and no COVID-related hospitalizations.

Interferons are known to have some anti-viral effects, Garjani said. In fact, interferon is one of several existing drugs that scientists have considered as possible candidates to fight COVID infection.

Studies on COVID infection rates and vaccine efficacy have yielded conflicting results. Some suggest no differences based on DMT use whereas others have shown immunological evidence pointing to lower or higher infections rates among the different therapies.

Based on some of those findings, up to 80% of specialists who treat MS in the US said the pandemic may have changed their use of DMTs, one study found, which later studies suggested may not have been necessary.

While the findings shouldn't necessarily prompt clinicians to consider changing their treatment approach, Garjani noted that her team tells patients who have not yet started treatment to get vaccinated before initiating MS treatment.

A Balancing Act

Commenting on the findings for Medscape Medical News, Tyler Smith, MD, clinical assistant professor of neurology at NYU Grossman School of Medicine, said that although the data suggest these MS therapies may affect COVID vaccine efficacy to varying degrees, there's more to the story.

Dr Tyler Smith

"This data builds upon a growing body of evidence that these treatments may attenuate vaccine responses to different degrees, and this should be balanced with their efficacy in controlling multiple sclerosis relapses, Smith said, adding that "real-life studies examining the effect of vaccines show benefit in limiting hospitalization and death."

"Developing evidence continues to demonstrate the benefits of vaccination," he said, "and I encourage all patients to follow the latest federal health guidelines regarding COVID-19 vaccinations."

Garjani has received personal compensation for serving as a speaker with MS Academy and Biogen. Smith's 2020-2021 fellowship was supported in part by Biogen and the National Multiple Sclerosis Society Clinical Care Physician Fellowship 2020-2021. Smith also received honoraria from the American Academy of Neurology in 2020.

American Academy of Neurology (AAN) 2022 Annual Meeting: Effectiveness of COVID-19 Vaccines in Multiple Sclerosis Patients Receiving Disease-Modifying Therapies in England. Presented April 3 and April 5, 2022, respectively.

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