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 Rheumatol. 2023 Feb;75(2):171-177. doi: 10.1002/art.42318. Epub 2022 Dec 7.

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.

Trial registration: ClinicalTrials.gov NCT05069714.

Publication types

  • Randomized Controlled Trial
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antirheumatic Agents* / therapeutic use
  • Arthritis, Rheumatoid*
  • Humans
  • Influenza A Virus, H1N1 Subtype*
  • Influenza A Virus, H3N2 Subtype
  • Influenza Vaccines* / administration & dosage
  • Influenza, Human* / chemically induced
  • Influenza, Human* / drug therapy
  • Influenza, Human* / prevention & control
  • Methotrexate / therapeutic use
  • Prospective Studies
  • Seasons
  • Vaccination

Substances

  • Antirheumatic Agents
  • Influenza Vaccines
  • Methotrexate

Associated data

  • ClinicalTrials.gov/NCT05069714