Trial Finds 1-Week Methotrexate Hold As Effective for Vaccine Response as 2-Week Hold

Jin Kyun Park, MD

New data from a randomized trial suggests discontinuing methotrexate in patients with rheumatoid arthritis for one week following a season influenza vaccination may be as effective as a two-week hold for immediate and long-term vaccine response.

A 178-person trial conducted in South Korea, results of the study, which were presented at American College of Rheumatology (ACR) Convergence 2022, indicate holding methotrexate for one week as opposed to 2 weeks did not significantly reduce rate of positive response at 4 weeks, with a control group without an autoimmune disease acting as a reference group for the trial.

“Patients and physicians alike do not often know what to do with methotrexate when a vaccination, including the annual flu vaccine or novel COVID-19 vaccines, is required. It was relieving to find out that skipping methotrexate for one week is as effective as skipping it for two weeks to improve vaccine response with no increase in disease flare risk,” said Jin Kyun Park, MD, Chief of Rheumatology at Seoul National University Hospital, associate professor at Seoul National University College of Medicine, in a statement from the ACR. “But it is not clear yet whether skipping methotrexate for one week improves response to other vaccines.”

Together with a team of colleagues, Park the current study was launched as a prospective, randomized, parallel-group, multicenter, noninferiority trial study with an interest in examining whether or not the aforementioned strategy of a one week holding period for methotrexate use following season influenza vaccination. With this in mind, investigators enrolled and randomized adult patients with rheumatoid arthritis recruited from 14 tertiary medical centers in South Korea in a 1:1 ratio to hold MTX for 1 week or 2 weeks after receiving the quadrivalent 2021–2022 seasonal influenza vaccine containing H1N1, H3N2, B-Yamagata, and B-Victoria strains.

For the purpose of analysis, the proportion of patients with a satisfactory vaccine response served as the primary outcome of interest for the trial. Investigators defined a satisfactory vaccine response as a 4-fold or greater increase in hemagglutination inhibition antibody titers the proportion of patients with a satisfactory vaccine response against 2 or more of the 4 vaccine strains 4 weeks after vaccination. The trial also included multiple secondary outcomes related to positive response and antibody titers at 4 and 16 weeks after vaccination. Investigators pointed out adults without autoimmune disease were included as a reference population.

Overall, 178 adult patients with rheumatoid arthritis were recruited and underwent randomization in the trial. Of these, 90 were randomized to withholding methotrexate for one week and 88 were randomized to withholding methotrexate for the standard 2 weeks.

Upon analysis, results of the trial indicated the proportion of satisfactory vaccine responses observed at 4 weeks did not differ significantly between those with a 1-week hold and those with a 2-week hold (68.9% vs 75.0%, P=.364). Analysis of secondary outcomes of interest demonstrated this trend persisted through 16 weeks (69.6% vs 70.3%, P=.915). Further analysis suggested the proportion of patients reaching seroprotection and the rise in antibody titer were similar between the groups at 4 and 16 weeks. Additionally, comparisons of responses between the rheumatoid arthritis and the control group without autoimmune disease were similar.

This study, “Immediate and Long-term Effects of the MTX Discontinuation for 1 vs. 2 Weeks on Vaccine Response to Seasonal Influenza Vaccine: A Non-inferiority Randomized Controlled Trial,” was presented at ACR Convergence 2022.