Influenza Vaccination As Model for Testing Immune Modulation Induced by Anti-TNF and Methotrexate Therapy in Rheumatoid Arthritis Patients

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.