Methotrexate reduces immune response to mRNA COVID-19 vaccine

Thursday, 27 May 2021


Up to a third of patients taking methotrexate fail to achieve an adequate immune response to mRNA COVID-19 vaccines, a small observational study reports.

Published in the Annals of the Rheumatic Diseases the trial involved 51 patients with rheumatoid arthritis, psoriatic arthritis or psoriasis who were taking methotrexate, anti-TNFs or biologics from New York University Langone Health, New York and 26 matched healthy controls.

A second validation cohort of controls (n=182) and patients with immune-mediated inflammatory diseases (n=31) from Erlangen, Germany were also analysed for humoral immune response.

All participants received the BNT162b2 mRNA vaccination and were assessed at baseline and after their second immunisation.

Results showed that adequate antibody levels were produced in over 90% of the 208 healthy participants and 37 patients on biologic or non-methotrexate oral treatments, but in only 62% of the 45 patients taking methotrexate.

While the vaccination induced activated CD8+ T cell responses in healthy participants and patients with immune-mediated inflammatory diseases not on methotrexate, this same induction was not seen in those patients on methotrexate.

The authors noted that IMID patients on methotrexate were generally older than the comparison group (average age 63 vs 49) which might potentially explain some differences in immunogenicity.

“Although precise cut offs for immunogenicity that correlate with vaccine efficacy are yet to be established, our findings suggest that different strategies may need to be explored in patients with immune-mediated inflammatory diseases taking methotrexate to increase the chances of immunisation efficacy against SARS-CoV-2 as has been demonstrated for augmenting immunogenicity to other viral vaccines,” the researchers conclude.

“Our results suggest that the optimal protection of patients with IMID against COVID-19 will require further studies to determine whether additional doses of vaccine, dose modification of methotrexate, or even temporary discontinuation of this drug can boost immune response as has been demonstrated for other viral vaccines in this patient population,” they added.

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