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Methotrexate holiday linked to better flu vaccine immunogenicity


AT ACR 2017

– Patients with well-controlled rheumatoid arthritis (RA) fared well during a 2-week holiday from methotrexate after flu vaccination and later showed signs of boosted immunity against the flu in comparison with patients who had not stopped the drug, according to results from a randomized controlled trial.

The research doesn’t confirm that vaccinated patients who take a break from methotrexate actually have lower rates of flu. Still, the findings suggest that brief holidays from methotrexate could be feasible in a variety of situations, such as after vaccinations and prior to surgery, said Jin Kyun Park, MD, of Seoul (South Korea) National University Hospital, lead author of the study presented at the annual meeting of the American College of Rheumatology.

A picture of vaccines and a syringe copyright DesignPics/Thinkstock
For now, Dr. Park said that he has advice for well-controlled RA patients who seek a flu vaccine: “I tell them to skip the next two doses of methotrexate, giving them a total of 2 weeks off. It doesn’t increase the risk of a flare, so you don’t risk anything by doing that.”

The study notes that RA patients are especially prone to infections for two reasons: dysfunctional immune systems and immunity-weakening treatments. According to Dr. Park, methotrexate reduces the effectiveness of flu vaccines by 15%-20%.

In a previous study, Dr. Park and his colleagues found no statistically significant sign of increased flares in patients who went without methotrexate for 2 weeks before and 2 weeks after vaccination, 4 weeks after vaccination, and 4 weeks before vaccination (Ann Rheum Dis. 2017 Sep;76[9]:1559-65).

The earlier findings also suggested that flu vaccine uptake is highest in those who stop methotrexate after vaccination.

For the new study, a randomized controlled trial, researchers recruited patients with well-controlled RA. They assigned 159 to continue weekly doses of methotrexate after flu vaccination and 161 to stop it for 2 weeks.

The groups in the final analysis (156 and 160 subjects, respectively) were similar – about 85% women, average age of 52-53 years, and about half took glucocorticoids. Their methotrexate dose per week was about 13 mg.

At 4 weeks, just over three-quarters of the patients who had briefly stopped methotrexate showed at least a fourfold increase in hemagglutination inhibition antibody titer against two or more vaccine strains. Of those who continued the medication, just 54.5% showed this level of response, which the researchers considered to be satisfactory.

The researchers reported that there was no appreciable increase in RA disease activity.

Dr. Park cautioned that vaccine titers don’t directly reflect immunoprotection levels. Patients who took a break from methotrexate were less likely to develop a flulike illness, but the difference wasn’t statistically significant.

The research raises questions about whether methotrexate could be stopped a week or two before surgery to lower the risk of infections, Dr. Park said.

Dr. Park said that future research should focus on whether stopping methotrexate briefly affects whether patients go on to develop the flu. He would also like to look at whether a break from the medication will boost the immune response in RA patients who get herpes zoster (shingles) vaccines.

Paul Sufka, MD, of HealthPartners and Regions Hospital in St. Paul, Minn., praised the research. The 2-week break from methotrexate is “a fairly pragmatic approach,” said Dr. Sufka, who moderated a press conference where Dr. Park presented his research.

“You can actually pull this off,” he said, versus telling patients to stop the medication for the 2 weeks before they get vaccinated. He cautioned, however, that “these people have a fairly low disease activity. You may not be able to pull this off with those who have high disease activity.”

Dr. Park and Dr. Sufka reported no relevant disclosures. A study author reported consulting for Pfizer and receiving research grants from Green Cross Corp. and Hanmi Pharmaceutical. The study was funded by Green Cross.

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