Methotrexate Drug Holiday Improves Flu Vaccine Effectiveness in RA

Methotrexate Drug Holiday Improves Flu Vaccine Effectiveness in RA

Here's a possible way to improve influenza vaccination effective in rheumatoid arthritis patients: a drug holiday from methotrexate for two weeks after immunization. Find out why researchers believe the system works and probably can be expanded to other vaccines.

SAN DIEGO – Effectively immunizing some chronically ill patients against influenza can be difficult.

For example, a presentation at the recent American College of Rheumatology (ACR)/Association of Rheumatology Health Professionals (AHRP) annual meeting discussed how methotrexate (MTX), a widely used immune-suppressive agent, decreases vaccine response in patients with rheumatoid arthritis (RA).

South Korean researchers investigated a possible solution, however. They looked at the effect of a temporary MTX discontinuation for two weeks after vaccination, seeking to determine if that would improve the efficacy of seasonal influenza vaccination in RA patients.

"RA patients are more susceptible to infections, including seasonal flu, due to their underlying abnormal immune function and the treatment-associated immune suppression," explained lead author Jin Kyun Park, MD, assistant professor of medicine at Seoul National University Hospital. "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. However, the immune suppression decreases vaccine response. 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."

The prospective, multicenter, randomized, parallel-group trial randomly assigned more than 300 RA patients taking stable doses of MTX at a ratio of 1:1 to continue MTX (MTX-continue group) or to suspend MTX for two weeks after vaccination (MTX-hold group).

All participants were vaccinated with seasonal quadrivalent influenza vaccine containing H1N1, H3N2, B-Yamagata, and B-Victoria, with the primary outcome defined as frequency of satisfactory vaccine response. To determine that, the researchers looked for a greater than four-fold increase in hemagglutination inhibition (HI) antibody titer at for weeks after vaccination against two or more of four vaccine strains. Seroprotection rate, fold-change in antibody titers relative to baseline in geometric mean titer (GMT) were considered secondary endpoints.

Results indicate that a higher proportion of patients in the MTX-hold group achieved satisfactory vaccine response compared to the MTX-continue group -- 75.5% vs. 54.5%. In addition, post-vaccination seroprotection rate was higher for all four antigens in the MTX-hold group than the MTX-continue group:

• H1N1: 75.6% vs. 86.3%,
• H3N2: 62.2% vs.78.1%,
• B-Yamagata: 74.4% vs. 88.1%,
• B-Victoria: 60.9% vs. 75.6%

At the same time, the MTX-hold group achieved higher fold increase of post-vaccination HI antibody titer in GMT for each antigen. The researchers also note that disease activity after vaccine didn't vary between groups.

Park suggested the approach "can be applied to other vaccines, such as pneumonia or zoster. Also, despite the well-known clinical experience that joint symptoms improve three to six weeks after starting methotrexate, our findings indicate that the drug has immediate effects on immune response. Short-term methotrexate discontinuation could be considered in situations of immunologic challenges such as infections or surgery."

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