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 (Hoboken). 2014 Jul;66(7):1016-26. doi: 10.1002/acr.22246.

Abstract

Objective: To assess the current literature on the impact of rheumatoid arthritis (RA) treatments on the humoral response to pneumococcal and influenza vaccines.

Methods: We systematically searched the literature for studies evaluating the immune response to vaccines in RA patients receiving methotrexate (MTX) and/or biologic agents. The efficacy of vaccination, assessed by the response rate based on increased antibody titers before and 3-6 weeks after vaccination, was extracted by one investigator and verified by another.

Results: In total, 12 studies were included. RA patients mainly received MTX, anti-tumor necrosis factor α (anti-TNFα), or rituximab (RTX). Influenza vaccination response was reduced for RTX (43 patients; pooled odds ratio [OR] 0.44 [95% confidence interval (95% CI) 0.17-1.12] for H1N1, OR 0.11 [95% CI 0.04-0.31] for H3N2, and OR 0.29 [95% CI 0.10-0.81] for B) but not for anti-TNFα (308 patients; OR 0.93 [95% CI 0.36-2.37] for H1N1, OR 0.79 [95% CI 0.34-1.83] for H3N2, and OR 0.79 [95% CI 0.37-1.70] for B). For MTX, results differed depending on the method of analysis (222 patients; OR 0.35 [95% CI 0.18-0.66] for at least 2 strains, ORs were close to 1.0 in the single strain analysis). Pneumococcal vaccination response was reduced for 139 patients receiving MTX compared with controls (OR 0.33 [95% CI 0.20-0.54] for serotype 6B and OR 0.58 [95% CI 0.36-0.94] for 23F) but not for anti-TNFα (258 patients; OR 0.96 [95% CI 0.57-1.59] for 6B and OR 1.20 [95% CI 0.57-2.54] for 23F). For RTX, the response was reduced (88 patients; OR 0.25 [95% CI 0.11-0.58] for 6B and OR 0.21 [95% CI 0.04-1.05] for 23F).

Conclusion: MTX decreases humoral response to pneumococcal vaccination and may impair response to influenza vaccination. The immune response to both vaccines is reduced with RTX but not with anti-TNFα therapy in RA patients.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Antibodies, Monoclonal, Murine-Derived / adverse effects*
  • Antirheumatic Agents / adverse effects*
  • Down-Regulation / drug effects*
  • Down-Regulation / immunology*
  • Humans
  • Immunity, Humoral* / drug effects
  • Influenza Vaccines / antagonists & inhibitors
  • Influenza Vaccines / immunology*
  • Influenza Vaccines / therapeutic use
  • Methotrexate / adverse effects
  • Pneumococcal Vaccines / antagonists & inhibitors
  • Pneumococcal Vaccines / immunology*
  • Pneumococcal Vaccines / therapeutic use
  • Rituximab
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors

Substances

  • Antibodies, Monoclonal, Murine-Derived
  • Antirheumatic Agents
  • Influenza Vaccines
  • Pneumococcal Vaccines
  • Tumor Necrosis Factor-alpha
  • Rituximab
  • Methotrexate