Risk of tuberculosis in patients treated with tumor necrosis factor antagonists due to incomplete prevention of reactivation of latent infection

Authors

  • Juan J. Gómez-Reino,

    Corresponding author
    1. Hospital Clínico Universitario, University of Santiago de Compostela School of Medicine, Santiago, Spain
    • Rheumatology, Hospital Clínico Universitario, A Choupana s/n, 15706 Santiago, Spain
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    • Drs. Carmona and Gómez-Reino contributed equally to this work.

    • Dr. Gómez-Reino is on the advisory boards of Wyeth and Roche and has received lecture fees (less than $10,000 each) from Abbott, Roche, Wyeth, and Schering-Plough.

  • Loreto Carmona,

    1. Spanish Foundation of Rheumatology, Madrid, Spain
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    • Drs. Carmona and Gómez-Reino contributed equally to this work.

  • Miguel Ángel Descalzo

    1. Spanish Foundation of Rheumatology, Madrid, Spain
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Abstract

Objective

To evaluate the causes of new cases of active tuberculosis (ATB) in patients treated with tumor necrosis factor (TNF) antagonists included in the national registry BIOBADASER (Base de Datos de Productos Biológicos de la Sociedad Española de Reumatología) after the dissemination of recommendations to prevent reactivation of latent tuberculosis infection (LTBI).

Methods

Incidence rate of ATB per 100,000 patient-years and 95% confidence intervals (95% CIs) were calculated in patients entering BIOBADASER after March 2002 and were stratified by compliance with recommendations (complete or incomplete). ATB rates in BIOBADASER were compared with the background rate and the rate in the rheumatoid arthritis cohort EMECAR (Estudio de la Morbilidad y Expresión Clínica de la Artritis Reumatoide) not treated with TNF antagonists. In addition, rates of ATB among patients treated with adalimumab, etanercept, and infliximab were estimated and compared only for treatments started after September 2003, when all 3 drugs became fully available.

Results

Following March 2002, a total of 5,198 patients treated with a TNF antagonist were registered in BIOBADASER. Fifteen ATB cases were noted (rate 172 per 100,000 patient-years, 95% CI 103–285). Recommendations were fully followed in 2,655 treatments. The probability of developing ATB was 7 times higher when recommendations were not followed (incidence rate ratio 7.09, 95% CI 1.60–64.69). Two-step tuberculosis skin test for LTBI was the major failure in complying with recommendations.

Conclusion

New cases of ATB still occur in patients treated with all available TNF antagonists due to lack of compliance with recommendations to prevent reactivation of LTBI. Continuous evaluation of recommendations is required to improve clinical practice.

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