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Reduced seroprotection after pandemic H1N1 influenza adjuvant-free vaccination in patients with rheumatoid arthritis: implications for clinical practice
  1. Ana C M Ribeiro1,
  2. Lissiane K N Guedes1,
  3. Julio C B Moraes1,
  4. Carla G S Saad1,
  5. Nadia E Aikawa1,2,
  6. Ana Luisa Calich1,
  7. Ivan L A França3,
  8. Jozelio F Carvalho1,
  9. Percival D Sampaio-Barros1,
  10. Celio R Goncalves1,
  11. Eduardo F Borba1,
  12. Maria do Carmo S Timenetsky4,
  13. Alexander R Precioso5,
  14. Alberto Duarte4,
  15. Eloisa Bonfa1,
  16. Ieda M M Laurindo1
  1. 1Division of Rheumatology, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil
  2. 2Pediatric Rheumatology Unit, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil
  3. 3Division of Infectology, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil
  4. 4Instituto Adolfo Lutz, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil
  5. 5Instituto Butantan–Fundação, São Paulo, Brazil
  1. Correspondence to Ieda Laurindo, Disciplina de Reumatologia, Faculdade de Medicina da Universidade de São Paulo, Av. Dr. Arnaldo, no 455, 3o andar, sala 3190 – Cerqueira César, 05403-010 Sao Paulo, Brazil; monocyte{at}


Background Reduced response to pandemic (2009) H1N1 (pH1N1) vaccine in patients with rheumatoid arthritis (RA) was recently reported.

Objectives To evaluate the contribution of age, disease activity, medication and previous antibody levels to this reduced response.

Methods 340 adult RA patients and 234 healthy controls were assessed before and 21 days after adjuvant-free influenza A/California/7/2009 (pH1N1) vaccine. Disease activity (DAS28), current treatment and pH1N1 antibody titres were collected. Seroprotection, seroconversion and factor increase in geometric mean titre (GMT) were calculated and adverse events registered.

Results RA and controls showed similar (p>0.05) prevaccination GMT (8.0 vs 9.3) and seroprotection (10.8% vs 11.5%). After vaccination a significant reduction (p<0.001) was observed in all endpoints: GMT and factor increase in GMT, seroprotection and seroconversion rates. Disease activity did not preclude seroconversion or seroprotection and remained unchanged in 97.4% of patients. Methotrexate was the only disease-modifying antirheumatic drug associated with reduced responses (p=0.001). Vaccination was well tolerated.

Conclusions The data confirmed both short-term anti-pH1N1 vaccine safety and, different from most studies with seasonal influenza, reduced seroprotection in RA patients, unrelated to disease activity and to most medications (except methotrexate). Extrapolation of immune responses from one vaccine to another may therefore not be possible and specific immunisation strategies (possibly booster) may be needed. no NCT01151644.

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  • Funding This study was supported by grants from Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP #2010/10749-0 to EB), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPQ #303165/2008-1 to EFB, #300248/2008-3 to CAS, #300665/2009-1 to JFC and #301411/2009-3 to EB), Federico Foundation (to EFB, JFC, PDSB and EB) and Butantan Foundation. The authors would like to thank the subjects for their critical roles in this study, the staff of Hospital das Clinicas FMUSP, Adolfo Lutz Institute and Faculdade de Medicina da USP.

  • Competing interests None.

  • Ethics approval This study was conducted with the approval of the local Institutional Review Board, Faculdade Medicina, Universidade de São Paulo.

  • Provenance and peer review Not commissioned; externally peer reviewed.