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


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.


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).


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.