Suspending Methotrexate for Influenza Vaccination Save

Vaccinating our rheumatoid arthritis patients against influenza every year is a safety priorty. However immunosuppressive therapies pose a challenge to vaccine administration as their use can hamper vaccine immunogenicity. The current issue of Annals of Rheumatic Disease published the findings of a prospective single-center randomized parallel group study looking at the effects of temporarily discontinuing methotrexate on response to the seasonal trivalent influenza vaccine in RA patients living in Seoul, Korea.

Patients who were on a stable dose of methotrexate were randomized into one of 4 groups: 1) continued methotrexate, 2) held methotrexate for 4 weeks before vaccination, 3) held methotrexate for 2 weeks before and 2 weeks after vaccination, and 4) held methotrexate for 4 weeks after vaccination. Patients could continue taking prednisolone equivalent up to 10 mg daily. The primary endpoint was satisfactory vaccine response after 4 weeks, defined by a ≥4-fold increase in haemaglutination inhibition (HI) antibody titers. 

The per-protocol population included 199 patients across the four groups. They found that group 3 achieved higher satisfactory vaccine response against all 3 viral antigens compared to group 1 (51.0% vs 31.5%, p=0.044). The vaccine was well tolerated in all patients. 30% experienced an RA flare which was more common in groups 2 and 3 but not of statistical significance. 

While the authors were unable to enroll enough patients to meet their target due to short enrollment period (thus rendering this study underpowered), it still has important clinical implications and suggests that temporarily discontinuing methotrexate 2 weeks before and 2 weeks after influenza vaccination can significantly improve vaccine immunogenicity. It is unclear if the same result can be expected for patients with active RA. Also, further studies are needed to determine if this effect will result in lower incidence of influenza.