Methotrexate, an immunosuppressant commonly used for the treatment of autoimmune inflammatory arthritis, reduces the immunogenicity of COVID-19 vaccination, necessitating an optimized strategy for maximizing the vaccine response while controlling disease activity in these patients. Results from a new study published in Lancet Rheumatology suggest that withdrawal of methotrexate only after the second dose of a COVID vaccine is safe and effective in patients with rheumatoid arthritis (RA) or psoriatic arthritis (PsA).
The study presents the results of two parallel, assessor-masked randomized controlled trials: MIVAC I and MIVAC II. These trials assessed the effects of withholding methotrexate for 2 weeks after the first and second doses (MIVAC I) or after the second dose only (MIVAC II) of the ChAdOx1 nCoV-19 vaccine in patients with RA or PsA versus continuing treatment with methotrexate throughout.
In both trials, withholding methotrexate resulted in a higher anti-receptor binding domain (RBD) antibody titre 4 weeks after the second dose (the primary outcome) than continuation of methotrexate. In MIVAC II, but not in MIVAC I, the proportion of patients with a flare did not differ between the methotrexate hold group and the methotrexate continuation group.
Post-hoc analysis found no difference in anti-RBD antibody titres between participants who withheld methotrexate twice and those who withheld methotrexate only after the second vaccine dose. Overall, the results suggest that withholding methotrexate only after the second dose is as effective in improving the vaccine response as withholding methotrexate after both vaccine doses, and does not increase the risk of flare.
Skaria, T. G. et al. Withholding methotrexate after vaccination with ChAdOx1 nCov19 in patients with rheumatoid or psoriatic arthritis in India (MIVAC I and II): results of two, parallel, assessor-masked, randomised controlled trials. Lancet Rheumatol. https://doi.org/10.1016/S2665-9913(22)00228-4 (2022)
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McHugh, J. Optimizing methotrexate withdrawal during COVID vaccination. Nat Rev Rheumatol 18, 613 (2022). https://doi.org/10.1038/s41584-022-00856-7