Ocrevus, Gilenya May Limit Efficacy of COVID-19 Vaccines: UK Study

COVID-19 infection rates after widespread vaccination were significantly higher among multiple sclerosis (MS) patients on Ocrevus (ocrelizumab) or Gilenya (fingolimod) than in the general population, but not among MS patients given other immunosuppressive disease-modifying therapies (DMTs), a data study in England reports.

While information on patients’ vaccination status and timing in relation to DMTs was not available, these preliminary findings add to previous studies suggesting that Gilenya and B-cell-depleting therapies like Ocrevus may limit the efficacy of COVID-19 vaccines.

The study, “Impact of mass vaccination on SARS-CoV-2 infections among multiple sclerosis patients taking immunomodulatory disease-modifying therapies in England,” was published in the journal Multiple Sclerosis and Related Disorders.

COVID-19 vaccines work by training the body’s immune system to recognize SARS-CoV-2, the virus that causes the disease, allowing a faster and more potent immune response in case of a future exposure.

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December 22, 2021 News by Marta Figueiredo, PhD

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While several real-world studies continue to show that vaccination is effective at preventing COVID-19 infections and severe disease, “it is still unclear whether it offers the same level of protection to multiple sclerosis (MS) patients receiving immunomodulatory disease-modifying therapies,” the researchers wrote.

Immunomodulatory and immunosuppressive DMTs — the mainstay of MS treatment — generally work by suppressing the immune system to lower the abnormal immune responses that drive nerve cell damage in MS.

An increasing number of studies suggest that this immunosuppression may also dampen the effectiveness of vaccines and to a greater degree with some of these DMTs than others.

Particularly, an earlier U.K. study that analyzed blood levels of antibodies against SARS-CoV-2 in nearly 500 vaccinated MS patients associated treatment with Gilenya or B-cell-depleting DMTs with a weaker vaccine response relative to other DMTs.

Novartis’ Gilenya is an oral therapy that works by “trapping” immune cells in lymph nodes, while B-cell-depleting DMTs, such as Genentech’s Ocrevus, work by promoting the death of immune B-cells. These cells are responsible for making antibodies not only against potential threats like viruses, but in autoimmune conditions such as MS against healthy cells and molecules as well.

A team of researchers in the U.K. now looked at changes in the risk of infection among all MS patients receiving DMTs in England following that country’s mass COVID-19 vaccination by retrospectively analyzing and comparing data from MS patients and the general adult population.

Infection rates among MS patients on DMTs and adults in general were assessed between March 2020 and August 2021. Comparisons between the groups were performed for the pre-vaccination (November 2020 to January 2021) and post-vaccination (June to August 2021) periods.

A mean of 41,208 MS patients received DMTs each month from March 2020 to August 2021, and results found that 3,524 of them tested positive for SARS-CoV-2 infection (with or without symptoms) during this time.

While similar infection rates were observed before and after vaccination between the general adult population and MS patients on DMTs, Ocrevus and Gilenya were associated with significantly higher infection rates in the post-vaccination period.

Specifically, the infection rate ratio between patients on Ocrevus and the general population significantly rose from 1.13 in the pre-vaccination period (meaning that for each infection in the general population, 1.13 MS patients were also infected) to 1.79 during the post-vaccination period. Among those on Gilenya, the ratio increased from 0.87 to 1.40 in the same two periods.

Treatment with beta-interferons, such as EMD Serono’s Rebif and Biogen’s Avonex, was associated with a lower infection rate than the general population throughout the evaluated months. This finding is consistent with their known antiviral effects, the researchers noted.

These preliminary results suggest “a substantial increase in the risk of SARS-CoV-2 infection among patients on [Ocrevus] or [Gilenya] compared to the general population following the liberalization of COVID-19 restrictions and despite mass vaccination,” the researchers wrote.

As such, COVID-19 vaccines may “offer less protection against infection to patients taking [Ocrevus] or [Gilenya], who have an impaired immune response to vaccines, than the general population,” they wrote.

While patient data on COVID-19 vaccination status was not available at the time of the study, vaccination status among the MS population was expected to be equal to that of the general population, the team noted.

Still, future studies “using individual-level data on vaccination (including interval between vaccination and SARS-CoV-2 infection), antibody levels, infections, and disease severity are required to establish the benefits of current vaccination programs and offering third dose vaccines to patients with drug-induced immunosuppression,” the researchers added.

In addition, the effectiveness of vaccination in preventing COVID-19 symptoms and severe disease among MS patients taking DMTs remains unclear. More research is needed to assess the effects of DMT-associated reduced immune response to the vaccine on the risk of severe COVID-19 infection in this patient population.

In an announcement related to the study’s findings, the U.K.’s MS Society stated: “Our medical advisers say people on these two treatments should be extra careful to follow precautions, even if they’re fully vaccinated and have had a booster.”

Patients “should be even more careful if [they] have other risk factors too,” the society added.