Temporary Cessation of Methotrexate Improves Influenza Vaccine Response in RA

Influenza vaccination
Influenza vaccination
Temporary cessation of methotrexate after receiving the influenza vaccine improves the immunogenicity of vaccination in patients with rheumatoid arthritis.

SAN DIEGO — Temporary discontinuation of methotrexate for 2 weeks after receiving seasonal influenza vaccination improves the immunogenicity of vaccination in patients with rheumatoid arthritis (RA) without increasing RA disease activity, according to data presented at the 2017 ACR/ARHP Annual Meeting.

Jin Kyun Park, MD, assistant professor of medicine in the Division of Rheumatology at Seoul National University Hospital in Seoul, South Korea, presented the data at the meeting. Dr Park and colleagues conducted a prospective, multicenter, randomized trial of 316 patients with RA who were taking a stable dose of methotrexate. Participants were randomly assigned to continue taking methotrexate (n=156) or to suspend the medication for 2 weeks after receiving influenza vaccination (n=160).

All participants received the seasonal quadrivalent influenza vaccine containing H1N1, H3N2, B-Yamagata, and B-Victoria. The primary outcome of the trial was the frequency of satisfactory vaccine response, defined as a ≥4-fold increase in hemagglutination inhibition antibody titer at 4 weeks after vaccination against at least 2 of 4 vaccine strains.

The results showed that 75.5% of patients who discontinued methotrexate for 2 weeks achieved satisfactory vaccine response compared with 54.5% of patients who continued methotrexate (P<.001). The postvaccination seroprotein rate was higher for all 4 antigens among patients who discontinued methotrexate compared with those who continued methotrexate: H1N1 (75.6% vs 86.3%; P=.016), H3N2 (62.2% vs 78.1%; P=.002), B-Yamagata (74.4% vs 88.1%; P=.002), and B-Victoria (60.9% vs 75.6%; P=.005).

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Patients who discontinued methotrexate also achieved higher fold increase in postvaccination hemagglutination inhibition antibody titer in geometric mean titer for the 4 antigens compared with patients who continued methotrexate: H1N1 (4.6 vs 6.7; P=.017), H3N2 (4.3 vs 8.0; P<.001), B-Yamagata (3.1 vs 5.6; P<.001), and B-Victoria (2.9 vs 5.7; P<.001). The researchers found that the vaccine was well tolerated and that RA disease activity did not differ between groups.

With these results, Dr Park suggests that patients hold methotrexate for 2 weeks after vaccination to increase immunogenicity of the vaccine. He also stated that in the future, other patient populations who take methotrexate, such as patients with inflammatory bowel disease, could also benefit from a temporary methotrexate holiday.

Dr Park also noted that the current study measured antibody titer, which does not ensure protection against infection. “We need a prospective study ensuring that if we really hold [methotrexate] for 2 weeks, this will decrease infection for sure,” he added.


Park JK, Shin K, Ha YJ, et al. Temporary methotrexate discontinuation for 2 weeks improves immunogenicity of seasonal influenza vaccination in patients with rheumatoid arthritis: a randomized clinical trial. Presented at: 2017 ACR/ARHP Annual Meeting; November 3-8, 2017; San Diego, CA. Abstract 827.

This article originally appeared on Rheumatology Advisor