Influenza vaccination as model for testing immune modulation induced by anti-TNF and methotrexate therapy in rheumatoid arthritis patients.
OBJECTIVE
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.
Kapetanovic
M C
MC
Department of Rheumatology, Lund University Hospital, Kioskgatan 3, S-221 85 Lund, Sweden. meliha.crnkic@reum.lu.se
Saxne
T
T
Nilsson
J-A
JA
Geborek
P
P
D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D000914:Antibodies, Viral / Q000096:biosynthesis; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000276:immunology*; D004359:Drug Therapy, Combination; D000068800:Etanercept; D005260:Female; D006801:Humans; D007108:Immune Tolerance; D007121:Immunocompetence; D007074:Immunoglobulin G / Q000627:therapeutic use; D000069285:Infliximab; D007252:Influenza Vaccines / Q000276:immunology*; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*; D014611:Vaccination / Q000379:methods
D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D018501:Antirheumatic Agents; D007074:Immunoglobulin G; D007252:Influenza Vaccines; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab; D000068800:Etanercept; D008727:Methotrexate