Study Suggests Some Patients Taking Anti-Inflammatory Drugs May Have Weaker Immune Response to COVID-19 Vaccines

A lower antibody response found in one-fourth of patients taking methotrexate does not necessarily mean that these patients are not protected against COVID-19.

Nearly 25% of patients taking methotrexate for common immune system disorders exhibit a weaker immune response to COVID-19 vaccines, according to a new study published in Annals of Rheumatic Diseases.

Scientists have previously established that patients with rheumatoid arthritis who take methotrexate have a reduced response to seasonal flu vaccines. Because mRNA vaccines, such as the COVID-19 vaccine developed by Pfizer and BioNTech, use a new mechanism of action that patients’ bodies have not experienced before, the investigators sought to evaluate how well these patients are protected after vaccination.

According to the study, immune system disorders occur when the immune system is triggered abnormally, causing inflammation as immune cells rush into damaged or infected tissue. These illnesses, called immune-mediated inflammatory disorders, are typically treated with drugs such as methotrexate to reduce inflammation, according to the study.

To investigate patient responses to the Pfizer-BioNTech COVID-19 vaccine, researchers at the New York University Grossman School of Medicine analyzed the antibodies produced in each patient after receiving the vaccine. Once injected into the body, the investigators said vaccine ingredients are meant to trigger the production of antibodies, which then disable the viral target protein and tag it for removal from the body.

Notably, the lower antibody response in patients taking methotrexate does not necessarily mean that these patients are not protected against COVID-19, co-first study author Rebecca Haberman, MD, said in a press release.

“It is most important to state that patients should not be concerned about our study findings, as the majority of patients with immune system disorders are responding well to the mRNA vaccines,” Haberman said. “It is also possible that methotrexate is delaying, rather than preventing, an adequate immune response against COVID-19.”

The study enrolled healthy people and patients receiving treatment for common immune-mediated disorders, including rheumatoid arthritis, psoriatic arthritis, and psoriasis. Participants received 2 doses of the Pfizer-BioNTech mRNA COVID-19 vaccine and the investigators then analyzed blood samples to determine the amount of antibodies produced.

They found that more than 90% of healthy subjects and patients taking drugs other than methotrexate mounted strong antibody responses, whereas only 62% of people with immune-mediated inflammatory disorders who were taking methotrexate achieved an adequate response. Similarly, patients taking methotrexate did not show an increase in CD8 T cell activation after vaccination, unlike healthy patients and those taking anti-inflammatory drugs other than methotrexate.

“More research is needed to understand why such a significant proportion of people with common immune disorders who take methotrexate have deficiencies in mounting an antibody and cellular response,” said co-senior author Jose U. Scher, MD, in the press release. “This may not necessarily mean that the vaccine is not efficacious, but that alternate vaccine strategies need to be investigated.”

These alternatives could include discontinuing methotrexate when patients receive the vaccine, changing the dosage of methotrexate or potentially administering a booster shot. The research team is currently leading studies to determine which of these alternatives would work best.

REFERENCE

Patients Taking Methotrexate Respond Less Well to COVID-19 Vaccine. News release. NYU Langone Health; June 2, 2021. Accessed June 10, 2021. https://nyulangone.org/news/patients-taking-methotrexate-respond-less-well-covid-19-vaccine.