Methotrexate and tumor necrosis factor inhibitors independently decrease neutralizing antibodies after SARS-CoV-2 vaccination: updated results from the SUCCEED study

Pillar 4
Functional Genomics & Structure-Function of VOCs

COVID-19 remains a major public health concern, still ranking as one of the top causes of death in North America in 2024. This study investigated two medication exposures—methotrexate and tumor necrosis factor inhibitors (TNFi)—and immune responses to COVID-19 vaccines. These medications are often used in autoimmune conditions like inflammatory bowel disease, rheumatoid arthritis, psoriatic arthritis, spondyloarthritis, and lupus.

Researchers collected blood samples from 479 adults with these conditions, across six academic centers in Canada, from 2022 to 2023. They used blood samples taken after vaccination, to measure antibodies to neutralize the SARS-CoV-2 virus, both the original strain and Omicron variants (BA1 and BA5). Each participant provided samples at two time points, which were analyzed in five laboratories using distinct methods. Researchers adjusted for factors like age, sex, disease type, other medications, number and type of vaccines received, and any prior COVID-19 infections.

The results showed that both methotrexate and TNFi reduced the immune system’s ability to neutralize SARS-CoV-2 after vaccination. Specifically, participants on TNFi were about 44% less likely to have strong neutralization against the original and BA5 strains of the virus, while those on methotrexate showed even more reduced neutralization for the BA1 variant. These findings were consistent across individual lab analyses and pooled meta-analyses.

The study highlights that while COVID-19 vaccines provide protection, their effectiveness in people taking methotrexate or TNFi may be diminished. This suggests that patients using these medications should ensure that their vaccination status is up to date as per national and provincial guidelines. Overall, these results emphasize the importance of tailored strategies to ensure effective immunity in people with autoimmune diseases, as the virus continues to evolve and circulate.

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