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

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.