Background Influenza is a frequent infectious disease affecting more than 20% of the world population yearly. It can cause severe complications in patients with autoimmune inflammatory diseases, such as rheumatoid arthritis (RA). In immunocompromised patients vaccinations are especially recommended. Influenza vaccines are generally safe and effective. However, RA patients require cautiousness in terms of vaccine immunogenicity especially when treated with immunomodulatory drugs.
Objectives To determine the immunogenicity of a seasonal influenza vaccine in RA patients, its timeline and the influence of different medications on patients' immune response.
Methods 137 RA patients (38 males, 99 females, median age 33) and 54 healthy controls (HC; 11 males, 43 females, median age 54) were vaccinated with trivalent seasonal influenza vaccine (Sanofi Pasteur) containing purified haemagglutinins A/Brisbane/59/2007 (H1N1), A/Brisbane/10//2007 (H3N2), B/Brisbane/60/2008 (B). Sera were collected just before vaccination (baseline), 18-90 days and >180 days after vaccination. Measurement of antibodies against surface membrane proteins was performed using haemagglutination inhibition (HI) tests, while detection of antibodies against inner viral proteins of influenza A and influenza B viruses was tested by IgG and IgA ELISA.
Results Using HI test, at baseline, RA patients were seroprotected (antibody titres ≥40) against seasonal influenza viruses A(H1N1), A(H3N2) and B in 58% (79/137), 97% (133/137) and 90% (123/137) respectively, versus 74% (40/54), 100% (54/54) and 83% (45/54) in HC. At the time of vaccination the IgG and IgA titres against inner proteins of influenza A and B viruses tested with ELISA showed a distinct elevation in the vaccinated (HC and RA) vs. non-vaccinated groups. After vaccination, significantly increased median titres of HI for A (H1N1), A (H3N2) and B were observed in controls and in RA. Compared to adalimumab, etarnercept, tocilizumab, infliximab, methotrexate and leflunomide, rituximab-treated patients had the lowest % of patients with of HI elevation for all three antigens (44%, H1N1; 22% H3N2, 50% B), which confirmed previous seasonal flu vaccination data (1). Seroconversion (postvaccination antibody titers ≥40 in patients whose prevaccination titres were <10) in the RA group for A(H1N1) was transient and decreased at >180 days. Similarly, the seroresponse (seroconversion or fold increase in antibody titers ≥4 in patients whose prevaccination titers were ≥10) in RA patients did not persist >180 days.
Conclusions The seroresponse observed in RA compared to controls was higher for A (H1N1) but not for A (H3N2) and B. We found that vaccination largely tilts the balance from negative ELISA IgG and IgA titres to positive titres in those RA patients who respond with H1N1 >4-fold titre elevation. The immune responses (for all antigens tested) of treated RA patients are higher than non-treated patients for all medications used, except rituximab.
Eisenberg R.A. et al. Rituximab-treated patients have a poorer response to influenza vaccination. J Clin Immunol. 2013 Feb; 33(2):388-396.
Disclosure of Interest None declared
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