NEW YORK (Reuters Health)—Temporarily withholding methotrexate (MTX) can improve the efficacy of seasonal influenza vaccination in patients with rheumatoid arthritis (RA), according to a new randomized clinical trial.
Response was strongest in patients who discontinued MTX for two weeks before and two weeks after receiving the flu shot, Dr. Eun Bong Lee of Seoul National University College of Medicine in Korea and colleagues reported online May 3 in Annals of the Rheumatic Diseases.
MTX impairs response to the pneumococcal and seasonal influenza vaccines, particularly to “presumably novel antigens such as new pandemic H1N1 influenza antigen,” Dr. Lee and colleagues note.
To investigate whether halting MTX for four weeks around the time of immunization could improve response, the researchers randomly assigned 199 patients to either continue taking MTX or to stop MTX for four weeks before vaccination, for two weeks before and two weeks after, or for four weeks after immunization.
Satisfactory responses to all three antigens in the vaccine (i.e., at least a 4-fold increase in hemaglutination inhibition antibody titer) were seen in 51% of patients who stopped MTX for two weeks before and two weeks after, compared to 31.5% of those who didn’t stop the drug at all (p=0.044).
MTX suspension for four weeks before vaccination did not yield better results than continuing the drug without stopping, whereas suspending it for four weeks afterward showed a trend toward better results compared to not stopping at all.
Anti-H3N2 antibodies increased 12.2-fold in the before-and-after group and 10-fold for those who stopped MTX for four weeks after immunization, compared to 5.9-fold in patients who continued on MTX throughout. Anti-B-Yamagata antibody fold increases in those groups, respectively, were 4.7, 6.1, and 2.9.
Flares occurred in 24% to 39% of patients, with no significant difference between the groups. Almost all patients who had flares recovered when they began taking MTX again.
“Further studies that determine the optimal duration of MTX discontinuation that improves vaccine efficacy while avoiding RA flares are warranted,” the researchers write.
“These data suggest that the effect of MTX on immune cells is actually immediate, whereas the disease-modifying effects of MTX . . . may take significantly longer to evolve,” Dr. Lee and colleagues state. “The fact that discontinuing MTX improves immune responses to vaccines also supports the clinical practice that MTX be discontinued during acute (life-threatening) infections.”
Future research should investigate whether discontinuing MTX reduces the incidence of influenza or changes its disease course, they conclude.