Stop Methotrexate in RA Patients for 2 Weeks After Flu Shot

Damian McNamara

November 05, 2017

SAN DIEGO — For people with rheumatoid arthritis, immune response to the flu vaccine is significantly stronger when methotrexate therapy is discontinued for 2 weeks after immunization, results from a prospective multicenter randomized trial show. But this temporary cessation has no effect on rheumatoid arthritis disease activity.

The response was better by 15% to 20%, as expected, but there was no increase in the flare rate," said investigator Jin Kyun Park, MD, from Seoul National University Hospital in South Korea.

"I hope this study will mean that fewer physicians will be scared of giving the vaccine. We know we should give vaccines, but we don't always do that in the clinic," he said here at the American College of Rheumatology 2017 Annual Meeting.

The trial builds on a pilot study in which Dr Park and his colleagues assessed patients who temporarily stopped methotrexate for 4 weeks before vaccination, 2 weeks before and 2 weeks after vaccination, and 4 weeks after vaccination, or who continued methotrexate (Ann Rheum Dis. 2017;76:1559-1565). The results demonstrated that suspending methotrexate for 2 weeks after vaccination is the best way to increase the effectiveness of the flu vaccine with no increase in the risk for disease flares.

Improving Vaccine Effectiveness

When the vaccine is administered, "we ask patients to skip the next 2 weekly doses," Dr Park explained. People might be less compliant if they are asked to hold off on 2 weekly doses before coming to the clinic.

Because patients taking methotrexate could be at a higher risk for infection, preventive measures like flu vaccination are particularly important, he pointed out.

In the intent-to-treat analysis, 156 were randomized to continue their methotrexate and 160 people took a 2-week drug holiday after their flu shot.

All participants received the seasonal quadrivalent influenza vaccine, which contained H1N1, H3N2, B/Yamagata, and B/Victoria, from October 7, 2016 to January 9, 2017.

More patients who temporarily stopped methotrexate than continued achieved seroprotection related to each strain in the vaccine.

Table 1. Seroprotection 4 Weeks After Flu Vaccination

Flu Strain Suspended Methotrexate, % Continuous Methotrexate, % P Value
H1N1 86.3 75.6 .016
H3N2 78.1 62.2 .002
B/Yamagata 88.1 74.4 .002
B/Victoria 75.6 60.9 .005


A satisfactory vaccine response was defined as a fourfold increase in hemagglutination inhibition antibody titer, or more, at 4 weeks against two or more of the strains in the vaccine.

At 4 weeks, the increase in antibody titers from baseline was greater in the suspension group than in the continuous group.

Table 2. Mean Fold Increase in Hemagglutination Inhibition Antibody After Vaccination (Geometric Mean Titer)

Flu Strain Suspensed Methotrexate Continuous Methotrexate P Value
H1N1 6.7 4.6 .017
H3N2 8.0 4.3 <.001
B/Yamagata 5.6 3.1 <.001
B/Victoria 5.7 2.9 <.001


Some people have high antibody titers and some people have low titers, "but a high titer does not always truly translate into protection, so it's still a subject for further research," Dr Park said.

"It's a practical way to pull this off in real life," said Paul Sufka, MD, from HealthPartners in Minneapolis.

"Telling people who come to your clinic to skip the next two doses of methotrexate is a really reasonable thing to do as a clinician," he told Medscape Medical News.

The flu vaccine was well tolerated, the researchers report. The findings could be extrapolated to other vaccinations provided to people with rheumatoid arthritis being treated with methotrexate, Dr Park said.

Dr Park and Dr Sufka have disclosed no relevant financial relationships.

American College of Rheumatology (ACR) 2017 Annual Meeting: Abstract 827. Presented November 5, 2017.

Follow Medscape Rheumatology on Twitter @MedscapeRheum and Damian McNamara @MedReporter


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