Temporary Methotrexate Discontinuation Improves Seasonal Influenza Vaccine Immunogenicity

Temporarily discontinuing methotrexate (MTX) for 2 weeks following seasonal influenza vaccination improves the immunogenicity of the vaccine and does not increase disease activity in patients with rheumatoid arthritis (RA), according to a study published in the Annals of the Rheumatic Diseases

Treatment for RA often involves long-term use of disease-modifying anti-rheumatic drugs, such as MTX, which inhibit both cellular and humoral immunity.¹ Previous studies have shown that MTX significantly decreases the vaccine response to pneumococcal and seasonal influenza vaccines.^2-6 The investigators previously completed a pilot study demonstrating that temporary discontinuation of MTX after seasonal influenza vaccination could significantly increase immunogenicity, but a 4-week discontinuation was associated with an increased risk for RA flare.⁷

Therefore, the investigators conducted a prospective, randomized, parallel-group multicenter study in which 156 patients with RA continued MTX treatment after receiving a quadrivalent seasonal influenza vaccine, and 160 patients with RA held their MTX treatment for 2 weeks after vaccination.¹ They found that more patients in the group that held their MTX treatment for 2 weeks achieved a satisfactory vaccine response than the MTX-continue group (75.5% vs 54.5%, P<.001). The seroprotection rate was higher in the MTX-hold group than in the MTX-continue group for all 4 influenza antigens. The MTX-hold group also demonstrated a higher increase in antibody titers against all 4 influenza antigens (all P<.05), but the change in disease activity was similar in both groups.

“In conclusion, a temporary discontinuation of MTX for 2 weeks after vaccination improves the immunogenicity of a seasonal influenza vaccine in patients with RA on stable dose of MTX without appreciably increasing disease activity,” stated the researchers.

References

1. Park JK, Lee YJ, Shin K, et al. Impact of temporary methotrexate discontinuation for 2 weeks on immunogenicity of seasonal influenza vaccination in patients with rheumatoid arthritis: a randomised clinical trial [published online March 23, 2018]. Ann Rheum Dis. doi:10.1136/annrheumdis-2018-213222
2. Ribeiro AC, Guedes LK, Moraes JC, et al. Reduced seroprotection after pandemic H1N1 influenza adjuvant-free vaccination in patients with rheumatoid arthritis: implications for clinical practice. Ann Rheum Dis 2011;70:2144-2147.
3. Winthrop KL, Silverfield J, Racewicz A, et al. The effect of tofacitinib on pneumococcal and influenza vaccine responses in rheumatoid arthritis. Ann Rheum Dis 2016;75:687-695.
4. Kapetanovic MC, Kristensen LE, Saxne T, et al. Impact of anti-rheumatic treatment on immunogenicity of pandemic H1N1 influenza vaccine in patients with arthritis. Arthritis Res Ther 2014;16:R2.
5. McMahan ZH, Bingham CO. Effects of biological and non-biological immunomodulatory therapies on the immunogenicity of vaccines in patients with rheumatic diseases. Arthritis Res Ther 2014;16:506.
6. Hua C, Barnetche T, Combe B, et al. Effect of methotrexate, anti-tumor necrosis factor α, and rituximab on the immune response to influenza and pneumococcal vaccines in patients with rheumatoid arthritis: a systematic review and meta-analysis. Arthritis Care Res 2014;66:1016-1026.
7. Park JK, Lee MA, Lee EY, et al. Effect of methotrexate discontinuation on efficacy of  seasonal influenza vaccination in patients with rheumatoid arthritis: a randomized  clinical trial. Ann Rheum Dis 2017;76:1559-1565.