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25-05-2021 | COVID-19 | News

Methotrexate may impair immune response to COVID-19 vaccination

Author: Claire Barnard


medwireNews: Some patients with immune-mediated inflammatory diseases (IMID) treated with methotrexate may have a blunted immune response to messenger RNA vaccines against SARS-CoV-2, researchers report.

The study included 51 patients with IMID – predominantly psoriasis/psoriatic arthritis or rheumatoid arthritis – from New York University Langone Health, USA, and 26 healthy controls who received both doses of the Pfizer–BioNTech (BNT162b2) vaccine and were assessed for their immune response between December 2020 and March 2021.

The researchers report in the Annals of the Rheumatic Diseases that the 26 patients with IMIDs who were not taking methotrexate developed “robust antibody responses” 1 week after receiving their second dose of the vaccine. A total of 92.3% of this group developed an adequate humoral immune response, defined as titers of immunoglobulin G antibodies against the SARS-CoV-2 spike protein of at least 5000 units, as did 96.1% of healthy controls.

The 25 methotrexate-treated patients had reduced rates of adequate humoral response, however, at 72.0%.

Jose Scher (New York University Langone Health) and team found a similar pattern of results in a validation cohort of 31 patients with IMID and 182 healthy controls from Erlangen, Germany. When both cohorts were combined, the proportion of individuals with an adequate humoral immune response was 91.9% for non-methotrexate-treated patients with IMID and 98.1% for healthy controls, compared with just 62.2% of those taking methotrexate.

The researchers also evaluated cell-mediated immune responses in the US cohort, finding that spike-specific B cells, activated CD4+ T cells, and circulating T follicular helper cells were “induced similarly” in all groups following vaccination. However, they say that “activated CD8+ T cell responses were notably attenuated” in patients taking methotrexate.

“Thus, reduced induction of cytotoxic CD8+ T cell responses, combined with inconsistent induction of antibody responses, may further impair effectiveness of COVID-19 vaccines and render IMID patients on methotrexate more at risk of inadequate vaccine response,” write Scher and team.

They say that “[a]lthough precise cut offs for immunogenicity that correlate with vaccine efficacy are yet to be established,” the study results “suggest that different strategies may need to be explored in patients with IMID taking methotrexate,” such as additional vaccine doses or temporary methotrexate discontinuation.

Previous study results showed that suspending methotrexate for 2 weeks could boost influenza vaccine immunogenicity, and Scher et al say that further studies should be carried out to evaluate whether similar strategies could be effective for COVID-19 vaccination.

medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2021 Springer Healthcare Ltd, part of the Springer Nature Group

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Ann Rheum Dis 2021; doi:10.1136/annrheumdis-2021-220597