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.

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“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.

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  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.