2619 - Influenza A H1N1/2009 Vaccine in Rheumatic Disease Patients Under Anti-TNF Therapy:  Safety and Response

Wednesday, November 9, 2011: 12:00 PM
W194b (McCormick Place West)
Ivan L.A. França1, Ana C. M. Ribeiro1, Nadia E. Aikawa1, Carla G.S. Saad1, Ana L. G. Calich1, Julio C. B. Moraes1, Ieda Laurindo1, Joao Miraglia2, Maria A. Ishida3, Eloisa Bonfa1 and Clovis Silva1, 1Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil, 2Fundação Butantan, São Paulo, Brazil, 3Adolfo Lutz Institute, Sao Paulo, Brazil
Presentation Number: 2619

Background/Purpose: Immunogenicity and safety of a non-adjuvanted anti-influenza A H1N1/2009 vaccine were recently reported by our group in a large population of autoimmune rheumatic diseases (ARD) (Ann Rheum Dis 2011). There are, however, few data regarding the effect of anti-TNF therapy in antibody response to such vaccine. Therefore, the objective of this study was to evaluate immunogenicity and short-term safety of anti-influenza A H1N1/2009 vaccine in rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA) patients under anti-TNF therapy. 

Methods: One hundred thirty-four adult patients [RA (n=45), AS (n=61), PsA (n=28)] under anti-TNF agents (62 infliximab, 43 adalimumab and 29 etanercept) regularly followed in our Rheumatology Division and 125 age-matched healthy controls were vaccinated with a non-adjuvanted preparation of influenza A/California/7/2009 (H1N1) virus-like vaccine. All participants were evaluated pre- and 21 days post-vaccination and serology for anti-H1N1 was performed by hemagglutination inhibition (HI) assay. Seroprotection (HI antibody titer≥1:40), seroconversion (percentage of subjects with either a pre-vaccination HI titer < 1:10 and a post vaccination HI titer ≥ 1:40 or a pre-vaccination HI titer > 1:10 and a minimum four-fold rise in post-vaccination HI antibody titer) rates, geometric mean titres (GMTs) and factor increase (FI) in GMT (ratio of the GMT after vaccination to the GMT before vaccination) were calculated. The effect of concomitant drugs on vaccine response was assessed and adverse events were also evaluated.

Result: Patients and controls had comparable mean current age (43.8±13.1 vs. 45.7±12.2 years, p=0.233). Three weeks after immunization, seroconversion (61.2% vs. 70.4%, p=0.119) and seroprotection rates (64.9% vs. 75.2%, p=0.072) were similar in both groups, whereas the FI in GMT was significantly lower (7.29 vs. 11.54; p=0.0089) in patients versus controls. The assessment of the influence of concomitant use of other drugs in patients under anti-TNF showed a trend of a higher frequency of seroconversion rate in patients under diphosphate chloroquine compared to those without it (90.9% vs. 58.5%, p=0.05), but association with other drugs, such as prednisone, methotrexate and leflunomide did not interfere in the response (p>0.05). Local and systemic vaccine adverse events were mild and with similar frequencies in patients under anti-TNF and controls (p>0.05).

Conclusion: The overall immune response to influenza A H1N1/2009 in rheumatic disease patients under TNF blockage therapy is adequate with an excellent safety profile. (ClinicalTrials.gov, #NCT01151644) 

Keywords: adalimumab, anti-TNF therapy, etanercept, infliximab and vaccines

Disclosure: I. L. A. França, None; A. C. M. Ribeiro, None; N. E. Aikawa, None; C. G. S. Saad, None; A. L. G. Calich, None; J. C. B. Moraes, None; I. Laurindo, None; J. Miraglia, None; M. A. Ishida, None; E. Bonfa, none, 2 ; C. Silva, none, 2 .