ABSTRACT
OBJECTIVE: This clinical trial was conducted to investigate whether discontinuing methotrexate (MTX) for 1 week after seasonal influenza vaccination is noninferior to discontinuing for 2 weeks after vaccination in patients with rheumatoid arthritis (RA). METHODS: In this multicenter, prospective, randomized, parallel-group noninferiority trial, RA patients receiving a stable dose of MTX were randomly assigned at a ratio of 1:1 to discontinue MTX for 1 week or for 2 weeks after they received the quadrivalent 2021-2022 seasonal influenza vaccine containing H1N1, H3N2, B/Yamagata, and B/Victoria strains. The primary outcome measure was the proportion of patients with a satisfactory vaccine response, which was defined as ≥4-fold increase in antibody titers, as determined with the hemagglutination inhibition assay, against ≥2 of the 4 vaccine strains at 4 weeks after vaccination. RESULTS: The modified intent-to-treat population included 90 patients in the 1-week MTX hold group and 88 patients in the 2-week MTX hold group. The mean ± SD MTX doses were 12.6 ± 3.4 mg/week in the 1-week MTX hold group and 12.9 ± 3.3 mg/week in the 2-week MTX hold group. The proportion of satisfactory vaccine responses did not differ between the groups (68.9% versus 75.0%; P = 0.364). The rate of seroprotection and the fold increase in antibody titers for each of the 4 influenza antigens were similar between the groups. CONCLUSION: A temporary discontinuation of MTX for 1 week after vaccination was noninferior to a discontinuation of MTX for 2 weeks after vaccination, regarding induction of a satisfactory vaccine response to a seasonal influenza vaccine in patients with RA receiving a stable dose of MTX.