Stopping Methotrexate for 1 Week After Flu Vaccine May Work as Well as 2 Weeks

A 1-week hold of methotrexate was equally effective in terms of immediate and long-term influenza vaccine response in patients with rheumatoid arthritis (RA), according to a recent study.

Methotrexate is a first-line therapy for rheumatoid arthritis (RA) due to its efficacy, safety profile, and inexpensive cost.

However, it significantly reduces response to pneumococcal and seasonal influenza vaccines, especially novel strain antigens; prior studies showed that withholding methotrexate for 2 weeks after patients received the seasonal flu vaccine improved immunogenicity. This study aimed to determine whether a 1-week hold worked just as well.

For this prospective randomized parallel-group trial, 178 adult patients with RA were recruited from tertiary centers in South Korea. All met the American College of Rheumatology (ACR) criteria for RA and had been on a stable dose of methotrexate for at least 6 weeks.

Patients were randomly assigned to withhold methotrexate for 1 week (90 patients) or 2 weeks (88 patients) after receiving the quadrivalent 2021-2022 seasonal flu vaccine (H1N1, H3N2, B-Yamagata and B-Victoria strains).

A control group without an autoimmune disease acted as a reference.

The primary outcome was a positive response at 4 weeks post vaccination, defined as a 4-fold or greater increase in antibody titers against at least 2 of the vaccine strains. Secondary outcomes were positive response and antibody titers at 4- and 16-weeks post vaccination.

The proportion of patients achieving satisfactory vaccine responses were similar in the 1- and 2-week groups at 4 weeks and 16 weeks (69% versus 75% and 69.6% versus 70.3%, respectively). The vaccine responses in the patients with RA and controls were also similar.

The researchers said it is not yet known if the strategy will work in other vaccines; they next want to see if the approach can be applied to other disease modifiying therapies and vaccines.

Jin Kyun Park, MD, chief of rheumatology at Seoul National University Hospital, associate professor at Seoul National University College of Medicine, and the study’s lead author, said the main reason for undertaking the trial was to determine whether the time without methotrexate could be minimized to reduce the likelihood of disease flares.

“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,” he said in a statement.

The study was presented at ACR Convergence 2022, the ACR's annual meeting.