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Methotrexate impedes immunogenicity to BNT162b2 mRNA Covid-19 vaccine in IMIDs

According to research led by New York University’s School of Medicine, methotrexate adversely affects the humoral and cellular immune response to Covid-19 mRNA vaccines. Methotrexate is commonly used to treat immune-mediated inflammatory diseases (IMIDs) such as psoriasis and psoriatic arthritis.

“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 IMID taking methotrexate to increase the chances of immunization efficacy against SARS-CoV-2,” the researchers wrote. Their findings were published online ahead of print in the journal Annals of the Rheumatic Diseases (May 25, 2021).

To investigate the humoral and cellular immune response to mRNA Covid-19 vaccines in patients with IMIDs on immunomodulatory treatments, the researchers studied patients with an IMID at NYU Langone Health receiving the BNT162b2 mRNA vaccination.

Patients were assessed at baseline and after their second immunization. Healthy subjects served as controls. The study’s authors analyzed the IgG antibody responses to the spike protein for a humoral response. Additionally, cellular immune response to Covid-19 was further analyzed using high-parameter spectral flow cytometry.

A second independent, validation group of controls and patients with IMIDs from Germany were also studied for humoral immune response.

The results showed that more than 90% of healthy subjects and IMID patients on biologic treatments such as TNF blockers demonstrated a robust antibody response. However, patients with IMIDs receiving methotrexate achieved an adequate response in only 62.2% of cases. Further, IMID patients did not demonstrate an increase in CD8+ T cell activation after vaccination.

“These results suggest that patients on methotrexate may need alternate vaccination strategies such as additional doses of vaccine, dose modification of methotrexate, or even a temporary discontinuation of this drug,” the researchers wrote. “Further studies will be required to explore the effect of these approaches on mRNA vaccine immunogenicity.”

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