- To assess the effect of anti-tumor necrosis factor (TNF) alpha therapies on the immunogenicity of pneumococcal vaccination in patients with rheumatoid arthritis (RA) and ankylosing spondylitis (AS). A group of 16 consecutive patients (11 with RA and 5 with AS) treated either with infliximab or etanercept, and a control group of 17 age-matched RA patients treated with disease-modifying medications other than anti-TNF-alpha, received intradeltoid injection with 0.5 mL of pneumococcal vaccine. Pneumococcal polysaccharide (PPS)-specific IgG to 7 vaccine PPS (representing high- and low-prevalence serotypes) was measured by enzyme-linked immunosorbent assay in sera obtained before and 1 month after pneumococcal immunization. One month after vaccination, both groups had significant increases in the geometric mean concentration of capsule PPS-specific antibody and in the mean fold increase in antibody levels to all 7 serotypes, compared with prevaccination levels. However, compared with the control group, the TNF-alpha blockade-treated patients tended to have lower antibody increases for all the serotypes tested except serotype 14. In addition, lower proportions of TNF-alpha blockade-treated patients responded to pneumococcal vaccination compared with patients on other therapies. Similarly, more TNF-alpha blockade-treated patients were poor responders compared with patients not on anti-TNF-alpha treatment. Treatment of groups of patients with etanercept or infliximab does not impair their mean antibody responses to pneumococcal vaccination. However, a larger proportion of RA patients may not respond adequately to pneumococcal vaccination once on TNF-alpha blockade therapies. Consequently, pneumococcal vaccination before starting TNF-alpha blockade therapy is recommended.