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SAN DIEGO -- Rheumatoid arthritis (RA) patients who stopped their regular methotrexate dosing for 2 weeks after receiving influenza vaccination showed a modestly stronger immune response compared with those who stayed on the medication in a randomized trial, a researcher reported here.

In the trial, conducted during the 2016-2017 Northern Hemisphere flu season, antibody titers measured 4 weeks after vaccination were about 15%-20% higher in those taking the methotrexate holiday for each of the virus strains included in the standard quadrivalent vaccine, said Jin Kyun Park, MD, of Seoul National University Hospital in South Korea, at the American College of Rheumatology (ACR) annual meeting.

"Satisfactory vaccine response," defined as at least fourfold increase in anti-hemagglutinin antibody titers at week 4 for a given viral strain, was achieved for all four strains approximately 40% of recipients stopping methotrexate, versus 20% of those continuing on the drug.

No difference in disease flares was seen between study arms.

At an ACR press briefing, Park said the finding -- if confirmed in a prospective trial directly addressing clinical protection against infection, which this one did not -- -- could be practice changing.

He also suggested that the same results could well apply in other immune diseases for which methotrexate is prescribed, such as inflammatory bowel disease.

Methotrexate is an immunosuppressive agent well known to inhibit vaccine efficacy, and the question has arisen as to whether suspending the drug temporarily could allow patients to mount an effective response to vaccination without increasing risk of autoimmune disease flares. Park described a pilot study his group had conducted earlier, testing methotrexate holidays of various lengths in RA patients. For example, a 4-week cessation appeared to provide a strong boost to the vaccine immune response, but at the cost of a 40% increase in arthritis flares.

The group settled on 2 weeks as likely striking an optimal balance between vaccine efficacy and flare risk. For the , the group enrolled 320 RA patients on stable methotrexate dosing, with 316 analyzed for efficacy, randomized 1:1 to the holiday or continued treatment. Patients were allowed to stay on other disease-modifying agents such as biologics.

Patients were offered vaccination when they came for clinic visits; those agreeing to it were given the vaccine and then randomized to be told either to stop taking methotrexate for the next 2 weeks or to keep taking it. Antibody titers were measured at baseline and 4 weeks after vaccination.

Press briefing moderator Paul Sufka, MD, of HealthPartners and Regions Hospital in St. Paul, Minnesota, applauded the investigators' "pragmatic approach" in designing the drug holiday. "We could actually pull this off," he said, noting that it would be less practical to ask patients to stop methotrexate for 2 weeks before coming for vaccination rather than after.

The study's primary endpoint, the proportion of patients with satisfactory vaccine response to at least two of the four strains, was met by 75.5% of those taking the 2-week drug holiday versus 54.5% of those continuing on methotrexate (P<0.001). Secondary endpoints such as differences in geometric mean titer also significantly favored the drug-holiday group. Park told MedPage Today that the effect did not differ according to whether patients were also taking biologics; those also taking leflunomide seemed to get a bigger impact from the holiday.

Park acknowledged that the study was not designed to analyze protection against infection, but the findings for immune response should be reflected in lower rates of infection.

Sufka agreed that a clinical benefit would be expected. However, he noted that patients in the study generally had low arthritis disease activity, and that it may be less practical to withhold methotrexate, even for a short time, in those with more severely active disease.