Can you boost flu vaccine efficacy in RA patients on methotrexate?

Patients with rheumatoid arthritis (RA) who took a 2-week break from methotrexate treatment after their influenza vaccination had a greater vaccine response without an increase in RA disease activity, according to results of a study presented November 5 at the 2017 American College of Rheumatology/Association of Rheumatology Health Professionals Annual Meeting in San Diego, CA.

“RA patients are more susceptible to infections, including seasonal flu, due to their underlying abnormal immune function and the treatment-associated immune suppression,” said study investigator Jin Kyun Park, MD, assistant professor of medicine, Division of Rheumatology, Seoul National University Hospital, Seoul, South Korea. “RA patients taking methotrexate are at even higher risk of infection and infection-related complications, so it’s important that they be vaccinated against preventable infectious diseases.”

The problem: Methotrexate decreases the flu vaccine’s response in RA patients.

“To overcome this shortcoming, our group has been working on a novel immunization protocol for RA patients to optimize vaccine response, including increasing immunogenicity of flu vaccines,” Dr. Park said.

To test this protocol, Dr. Park and his fellow researchers conducted a multicenter, randomized trial in patients with RA who were taking methotrexate at a stable dose. The researchers enrolled 316 RA patients from October 2016 to January 2017 and randomly assigned them to two groups: 160 who discontinued methotrexate for 2 weeks after their flu shot and 156 who continued methotrexate after their shot. All patients were given a seasonal, quadrivalent vaccine containing H1N1, H3N2, B-Yamagata, and B-Victoria antigens.

The researchers found that 75.5% of patients who took a 2-week break from methotrexate had a satisfactory vaccine response, compared with 54.5% of patients who continued methotrexate. (Investigators defined a satisfactory vaccine response as a four-fold or greater increase in hemaglutination inhibition antibody titer against at least two of four vaccine strains at 4 weeks after vaccination.)

Seroprotection rates for all four antigen strains were also higher after vaccination among patients in the methotrexate discontinuation group compared with the continuation group.

Importantly, neither group experienced an increase in RA disease activity after vaccination.

Hold the methotrexate

“The findings of this study have several potential clinical implications,” Dr. Park said. “First, we show a novel, effective, but simple way to improve vaccine response in RA patients who take methotrexate. Holding methotrexate for 2 weeks after vaccination improved vaccine response significantly without increasing disease activity. Therefore, patients should be advised to hold methotrexate for 2 weeks after vaccination.”

Second, he suggested that this protocol could be applied to other vaccines, such as pneumonia or zoster virus, given the results of this study.

Third, “despite the well-known clinical experience that joint symptoms improve 3 to 6 weeks after starting methotrexate, our findings indicate that the drug has immediate effects on immune response,” Dr. Park said. “Short-term methotrexate discontinuation could be considered in situations of immunologic challenges such as infections or surgery.”

He added one cautionary note: This study only assessed antibody production after the flu shot, not actual incidence of flu among RA patients. “Since antibody production does not always guarantee immune protection, further studies are needed to address whether the increased immunogenicity by holding methotrexate for 2 weeks can prevent flu infection,” Dr. Park explained.