Methotrexate adversely affects immunogenicity to COVID-19 mRNA vaccines

Methotexate adversely affects humoral and cellular immunogenicity to COVID-19 mRNA vaccines in patients with immune-mediated inflammatory diseases (IMIDs) on immunomodulatory treatment.

This is the main finding of a study that investigated the humoral and cellular immune response to BNT162b2 mRNA vaccination among patients with IMID receiving disease-modifying anti-rheumatic drugs (DMARDs), with or without methotrexate, compared with healthy subjects. The study included two geographically independent cohorts: one from New York City, USA, and one from Erlangen, Germany.

The data analysis showed a decreased antibody response to the mRNA COVID-19 vaccine in IMID patients on methotrexate in both cohorts, as measured by testing IgG antibodies against the spike protein of SARS-CoV-2. The rates of adequate humoral response were substantially lower among IMID patients on methotrexate (18/25 [72.0%] in the New York cohort and 10/20 [50.0%] in the Erlangen cohort), compared with those among healthy participants (25/26 [96.1%] and 179/182 [98.3%], respectively) and those among IMID patients receiving no methotrexate (24/26 [92.3%] and 10/11 [90.9%], respectively). Immune cell phenotyping before and after vaccination in participants in the New York cohort showed a lack of CD8+ T-cell activation in up to a third of the IMID patients on methotrexate following the mRNA COVID-19 vaccine, whereas IMID patients on other DMARDs had a robust response similar to that of healthy controls. "Our results suggest that the optimal protection of patients with IMID against CODVID-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," conclude the researchers.