Immune-suppressing Medicines May Reduce COVID-19 Vaccine Efficacy

A class of immune-suppressing medications called TNF-alpha inhibitors can reduce the efficacy of vaccines for COVID-19, according to a study that included patients with multiple sclerosis (MS) and other autoimmune diseases.

The results also suggest that a third dose of a COVID-19 vaccine may help to protect patients with weakened immune systems.

Indeed, the study’s findings “suggest that those receiving [TNF-alpha inhibitors] in particular should be prioritized for additional vaccine doses,” according to the researchers.

The study, “Reduced antibody activity against SARS-CoV-2 B.1.617.2 Delta virus in serum of mRNA-vaccinated patients receiving Tumor Necrosis Factor-α inhibitors,” was published in the journal Med.

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Several vaccines for COVID-19 have become widely available since the outbreak of the global pandemic. Like vaccines for other diseases, these therapies work by “training” the body’s immune system to recognize the virus that causes COVID-19. In particular, vaccines promote the production of antibodies, which are specialized proteins that can bind to the virus. A particular kind of antibody called neutralizing antibodies, which can prevent the virus from infecting cells, is particularly important for vaccine-induced protection.

Although the available COVID-19 vaccines have been proven to be highly effective for preventing serious disease in healthy people, their efficacy in people with weakened immune systems — such as individuals on immune-suppressing medications — is not completely understood.

Now, a team of U.S.-based scientists analyzed the antibody response in 77 people with autoimmune diseases, including MS, inflammatory bowel disease, known as IBD, asthma, and other conditions.

Each of the patients was taking a single immune-suppressing medication. For comparison, data on 25 healthy people also were analyzed. All participants received the standard two doses of the Pfizer vaccine, produced by the U.S.-based pharmaceutical company and its German partner BioNTech.

The scientists tested the antibody response against the original strain of COVID-19, as well as the alpha, beta, and delta strains. Of note, most cases of COVID-19 in the U.S. currently are caused by the delta strain.

Results indicated that the antibody response was significantly impaired in patients who had been treated with TNF-alpha inhibitors. As the name suggests, these are a class of medications that block a pro-inflammatory signaling molecule called TNF-alpha (tumor necrosis factor-alpha).

TNF-alpha inhibitors include etanercept, infliximab, and adalimumab; these medications are commonly used to treat certain forms of arthritis and inflammatory bowel disease.

Data showed that, at three months after the second dose, 67% of patients on TNF-alpha inhibitors had antibody levels below the minimum thought necessary to provide protection against infection. In comparison, 36% of all immunosuppressed people had levels of antibodies below that threshold. Just 8% of healthy patients had levels below the minimum believed necessary.

The patients on TNF-alpha inhibitors also had substantially lower numbers of neutralizing antibodies, particularly against the delta variant.

By five months after vaccination, all of the tested patients on TNF-alpha inhibitors had antibody levels below the minimum needed to confer protection.

“People taking TNF inhibitors didn’t make as many of the potently inhibitory antibodies, and the ones that they did make had largely decayed by five months after the second dose,” Michael S. Diamond, MD, PhD, a professor at Washington University, in Missouri, and co-author of the study, said in a press release.

“So even when compared to other immunosuppressed people, people on TNF inhibitors are probably at greater risk for breakthrough infections, especially as immunity wanes and several months have passed since their initial vaccinations,” Diamond said.

Notably, data from four patients on TNF-alpha inhibitors who received a third “booster” dose of the vaccine showed that antibody levels increased by 16- to 25-fold, suggesting that these patients may benefit from further doses of vaccine.

“Our data suggests that they should get boosted,” Diamond said.

The team acknowledged several limitations of this study, most notably that the numbers for each specific treatment assessed were quite low, and participants were analyzed based on treatment regardless of their underlying condition.