Influence of methotrexate, TNF blockers and prednisolone on antibody responses to pneumococcal polysaccharide vaccine in patients with rheumatoid arthritis

Rheumatology (Oxford). 2006 Jan;45(1):106-11. doi: 10.1093/rheumatology/kei193. Epub 2005 Nov 15.


Objective: To compare antibody responses to 23-valent pneumococcal vaccine (Pneumovax) in controls and patients with established rheumatoid arthritis (RA) treated with TNF blockers, methotrexate (MTX) or a combination of both.

Methods: Patients with RA (n = 149) and healthy controls (n = 47) were vaccinated. Treatment with TNF blockers (etanercept or infliximab) and MTX was given to 50 patients, and 62 patients were treated with TNF blockers alone or with other DMARDs. MTX alone was given to 37 patients. Concentrations of immunoglobulin G (IgG) antibodies against pneumococcal capsular polysaccharides 23F and 6B were measured by enzyme-linked immunoassay before and 4-6 weeks after vaccination. An immune response was defined as a twofold or higher increase in antibody concentration following vaccination.

Results: Prevaccination antibody levels for both 23F and 6B were similar in the patient groups. Antibody concentrations after vaccination increased significantly in all groups. Patients treated with TNF blockers without MTX showed better immune responses than those treated with TNF blockers in combination with MTX (P = 0.037 for 23F and P = 0.004 for 6B) or MTX alone (P<0.001 for both 23F and 6B). RA patients given MTX alone had the lowest immune responses. Prednisolone treatment did not influence the responses.

Conclusions: Patients treated with TNF blockers and controls showed similar responses to vaccination. In contrast, patients treated with MTX had reduced responses regardless of anti-TNF treatment. The findings do not argue against the use of pneumococcal vaccination in RA patients undergoing treatment with TNF blockers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Anti-Inflammatory Agents / immunology
  • Anti-Inflammatory Agents / therapeutic use
  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / therapeutic use
  • Antibody Formation
  • Antirheumatic Agents / immunology*
  • Antirheumatic Agents / therapeutic use
  • Arthritis, Rheumatoid / drug therapy
  • Arthritis, Rheumatoid / immunology*
  • Case-Control Studies
  • Drug Combinations
  • Enzyme-Linked Immunosorbent Assay
  • Etanercept
  • Female
  • Humans
  • Immunoglobulin G / immunology*
  • Immunoglobulin G / therapeutic use
  • Infliximab
  • Male
  • Methotrexate / immunology
  • Methotrexate / therapeutic use
  • Middle Aged
  • Pneumococcal Infections / prevention & control
  • Pneumococcal Vaccines / immunology*
  • Prednisolone / immunology
  • Prednisolone / therapeutic use
  • Receptors, Tumor Necrosis Factor / immunology
  • Receptors, Tumor Necrosis Factor / therapeutic use


  • 23-valent pneumococcal capsular polysaccharide vaccine
  • Anti-Inflammatory Agents
  • Antibodies, Monoclonal
  • Antirheumatic Agents
  • Drug Combinations
  • Immunoglobulin G
  • Pneumococcal Vaccines
  • Receptors, Tumor Necrosis Factor
  • Prednisolone
  • Infliximab
  • Etanercept
  • Methotrexate