EFFICACY AND SAFETY OF VACCINATION IN RHEUMATOID ARTHRITIS PATIENTS TREATED WITH METHOTREXATE: A SYSTEMATIC LITERATURE RESEARCH

B. A. Cruz*1, I. M. M. Laurindo2, M. B. Bertolo3, R. D. Giorgi4, I. A. Pereira5
1Rheumatology, Biocor Instituto, Nova Lima, 2Rheumatology, Medical School, USP, São Paulo, 3Rheumatology, Medical School, UNICAMP, Campinas, 4Rheumatology, Hospital dos Servidores do Estado, São Paulo, 5Rheumatology, Medical School, UFSC, Florianópolis, Brazil

Background: Methotrexate (MTX) is the most prescribed disease modifying drug in Rheumatoid Arthritis (RA). There are no definitive recommendations regarding efficacy and safety of vaccination in RA patients treated with MTX. There is also a concern about the possibility that immunization may increase disease activity in those patients.

Objectives: To perform a Systematic Literature Research (SLR) about the efficacy and safety of vaccination in RA patients treated with MTX.

Methods: The 3E 2007-2008 is a multi-national initiative to develop evidence and expert based recommendations for the use of MTX in rheumatic diseases. Beside common clinical questions to be answered by an international bibliographic committee, there were specific questions to be developed by each national committee. The Brazilian committee performed a SLR focusing on the efficacy and the safety of vaccination in RA patients treated with MTX. Databases searched included Medline and Cochrane Clinical Trials from 1950 until June 2007 and EULAR/ACR abstracts 2005-2007. Keywords were RA, MTX, vaccination and/or immunization.

Results: Two hundred and six studies were initially retrieved for analysis that included predefined exclusion criteria. Studies were excluded mainly due to small sample size or design limitations that did not permit comparison between RA patients treated with MTX, a control group of RA patients on other treatment and/or healthy subjects. Eight studies were kept for final analysis. Four prospective open studies (n = 615) that evaluated Influenza vaccination and two prospective open studies (n = 258) that evaluated hepatitis B vaccination suggest that both vaccines are effective, safe and do not interfere with disease activity. Two prospective open studies (n = 77) suggest that pneumococcal vaccination is safe, does not interfere with disease activity, but may be less effective in RA patients on MTX in comparison with RA patients on other treatments and healthy subjects. The studies were heterogeneous regarding design and outcome, thus precluding a quantitative analysis.

Conclusion: There is evidence that vaccination against Influenza, Hepatitis B, and Pneumococcus is effective and safe in RA patients on MTX (Category of Evidence: 2b). Nevertheless, pneumococcal vaccination seems to be less effective in RA patients on MTX in comparison with healthy subjects and RA patients on other treatments. There are no data regarding the use of attenuated live viruses vaccinations in this population. The Brazilian expert Committee concluded that RA patients on MTX may receive vaccination against Influenza, Hepatitis B and Pneumococcus (Grade of Recommendation = B).