Results of their studies consistently showed that withholding methotrexate for one to two weeks after vaccination is sufficient to restore methotrexate-induced suppression of vaccine response, without significantly increasing the risk of RA disease flare.2,3
“Before our studies, it was unclear whether holding methotrexate around the time of vaccination could meaningfully improve vaccine-induced immune response,” Dr. Park said. “Our work was the first to demonstrate that a temporary discontinuation of MTX can indeed restore vaccine responsiveness to flu vaccine in these patients.”
He called the finding unexpected because it contradicted a widely held assumption that methotrexate has a long biologic half-life. Further research, Dr. Park said that in vitro pharmacokinetic studies demonstrated that intracellular methotrexate concentrations declined sharply within 24 hours after drug withdrawal.4 “This indicates that methotrexate is cleared from cells much more rapidly than previously believed,” he said.
Dr. Park emphasized that more clinical research is needed to define the optimal vaccination strategies for each immunosuppression regimen and patient population.
Mary Beth Nierengarten is a freelance medical journalist based in Minneapolis.
References
- Furer V, Weil C, Chodik G, et al. Real-world coverage with influenza, pneumococcal, and herpes zoster vaccines among patients with rheumatic diseases in a nationwide healthcare plan. J Rheumatol. 2024 May 1;51(5):505–516.
- Park JK, Lee YJ, Shin K, et al. A multicenter, prospective, randomized, parallel-group trial on the effects of temporary methotrexate discontinuation for one week versus two weeks on seasonal influenza vaccination in patients with rheumatoid arthritis. Arthritis Rheum. 2023 Feb;75(2):171–177.
- Park JK, Kim MJ, Choi Y, et al. Optimal time between the last methotrexate administration and seasonal influenza vaccination in rheumatoid arthritis: Post hoc analysis of a randomised clinical trial. Ann Rheum Dis. 2019 Sep;78(9):1283–1284.
- Park et al. Unpublished research. ACR Convergence 2025, Chicago.
