Antibody response is reduced following vaccination with 7-valent conjugate pneumococcal vaccine in adult methotrexate-treated patients with established arthritis, but not those treated with tumor necrosis factor inhibitors

Arthritis Rheum. 2011 Dec;63(12):3723-32. doi: 10.1002/art.30580.


Objective: To study the influence of antiinflammatory treatments, including methotrexate (MTX) and tumor necrosis factor (TNF) inhibitors, on antibody response following vaccination using a 7-valent conjugate pneumococcal vaccine in adult patients with established arthritis.

Methods: Patients with rheumatoid arthritis (RA) or spondylarthropathy (SpA) (including psoriatic arthritis) were vaccinated (n = 505). All patients were stratified into 6 prespecified groups based on diagnosis and treatment (RA patients receiving MTX, RA patients receiving anti-TNF agents and MTX, RA patients receiving TNF inhibitors as monotherapy, SpA patients receiving anti-TNF agents and MTX, SpA patients receiving TNF inhibitors as monotherapy, and SpA patients receiving nonsteroidal antiinflammatory drugs [NSAIDs] and/or analgesics). SpA patients receiving only NSAIDs/analgesics served as a control group. All patients received 1 dose (0.5 ml) of vaccine intramuscularly. Levels of IgG antibodies against 23F and 6B serotypes were measured at vaccination and at 4-6 weeks following vaccination, using standardized enzyme-linked immunosorbent assays.

Results: Positive antibody response was defined as an antibody response ratio (ARR) (i.e., ratio of post- to prevaccination antibody levels) of ≥2. The ARR differed significantly between the groups. A better ARR was seen among patients in the control group compared to those in groups treated with MTX or MTX in combination with TNF inhibitors. Among patients treated with TNF inhibitors as monotherapy, ARRs for both serotypes were lower numerically, but were not significantly different, compared to those in controls. Ongoing MTX treatment was predictive of reduced response (odds ratio 0.41 [95% confidence interval 0.24-0.68], P = 0.001). Higher age was associated with impaired positive antibody response. Concomitant prednisolone treatment elicited better positive antibody response in patients with RA.

Conclusion: Treatment with MTX and higher age were predictive of an impaired antibody response to the 7-valent conjugate pneumococcal vaccine in this cohort of patients with chronic arthritis. TNF inhibitors did not significantly affect antibody responses.

Trial registration: NCT00828997.

Publication types

  • Comparative Study
  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
  • Antibodies, Bacterial / blood*
  • Antibody Formation / drug effects
  • Antirheumatic Agents / pharmacology
  • Antirheumatic Agents / therapeutic use*
  • Arthritis, Psoriatic / drug therapy
  • Arthritis, Rheumatoid / drug therapy*
  • Drug Therapy, Combination
  • Female
  • Humans
  • Male
  • Methotrexate / pharmacology
  • Methotrexate / therapeutic use*
  • Middle Aged
  • Pneumococcal Vaccines / immunology
  • Pneumococcal Vaccines / therapeutic use*
  • Pneumonia, Pneumococcal / immunology
  • Pneumonia, Pneumococcal / prevention & control*
  • Spondylarthropathies / drug therapy
  • Streptococcus pneumoniae / immunology*
  • Treatment Outcome
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*


  • Anti-Inflammatory Agents, Non-Steroidal
  • Antibodies, Bacterial
  • Antirheumatic Agents
  • Pneumococcal Vaccines
  • Tumor Necrosis Factor-alpha
  • Methotrexate

Associated data