Influenza vaccination as model for testing immune modulation induced by anti-TNF and methotrexate therapy in rheumatoid arthritis patients

Rheumatology (Oxford). 2007 Apr;46(4):608-11. doi: 10.1093/rheumatology/kel366. Epub 2006 Nov 18.


Objectives: To compare serological response to influenza vaccine in patients with long-standing rheumatoid arthritis (RA) treated with tumour necrosis factor (TNF) blockers and/or methotrexate (MTX) and controls.

Methods: Altogether, 149 patients with RA and 18 healthy subjects were vaccinated. Fifty patients were treated with TNF blockers (etanercept or infliximab) in combination with MTX (TNF blockers + MTX), while 62 patients received TNF blockers alone or with other disease-modifying anti-rheumatic drugs (DMARDs) (TNF blockers without MTX). Thirty-seven patients were treated with MTX without TNF blockers (MTX). Vaccination was performed with trivalent vaccine (Influvax or Vaxigrip) both containing 15 microg haemagglutination inhibition (HI) of each of two A strains (H1N1 and H3N2) and one of B strains (B1 or B2). Serum samples were collected prior to and 4-6 weeks after vaccination and titrated against all four strains using HI assay. A positive immune response was defined as > or =4-fold increase compared with pre-vaccination titre levels. A titre > or =40 was considered protective. Pre- and post-vaccination geometric mean titres (GMT) were compared.

Results: Post-vaccination titre levels increased significantly in all groups, also reflected by high frequencies of positive immune responders. A positive immune response to combinations of all strains was significantly better for the MTX group. Individuals with protective levels before vaccination responded less well as a group.

Conclusions: RA patients treated with MTX without TNF blockers had significantly better serological response to influenza vaccination compared with those receiving TNF blockers alone or in combination with MTX and/or other DMARDs. However, the immune response is sufficiently large to warrant influenza vaccination to all RA patients regardless of treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal / therapeutic use
  • Antibodies, Viral / biosynthesis
  • Antirheumatic Agents / therapeutic use*
  • Arthritis, Rheumatoid / drug therapy
  • Arthritis, Rheumatoid / immunology*
  • Drug Therapy, Combination
  • Etanercept
  • Female
  • Humans
  • Immune Tolerance
  • Immunocompetence
  • Immunoglobulin G / therapeutic use
  • Infliximab
  • Influenza Vaccines / immunology*
  • Male
  • Methotrexate / therapeutic use
  • Receptors, Tumor Necrosis Factor / therapeutic use
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*
  • Vaccination / methods


  • Antibodies, Monoclonal
  • Antibodies, Viral
  • Antirheumatic Agents
  • Immunoglobulin G
  • Influenza Vaccines
  • Receptors, Tumor Necrosis Factor
  • Tumor Necrosis Factor-alpha
  • Infliximab
  • Etanercept
  • Methotrexate