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 (England), said in an interview.
Although the differences in infection rates and efficacy are significant in those two DMTs, the overall infection and hospitalization rates were low, Dr. Garjani noted, offering further evidence that vaccines are effective in most patients with MS.
The findings were presented at the 2022 annual meeting of the American Academy of Neurology.
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 in the fingolimod group was 0.50 (95% confidence interval, 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 time frame.
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,” Dr. 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,” Dr. 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 antiviral effects, Dr. 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 United States 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, Dr. Garjani noted that her team tells patients who have not yet started treatment to get vaccinated before initiating MS treatment.