Safety of Pyrazinamide for the Treatment of Tuberculosis in Older Patients Over 75 Years of Age: A Retrospective Monocen
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ORIGINAL RESEARCH ARTICLE
Safety of Pyrazinamide for the Treatment of Tuberculosis in Older Patients Over 75 Years of Age: A Retrospective Monocentric Cohort Study Stella Rousset1 · Margaux Lafaurie2,9 · Hélène Guet‑Revillet3 · Caroline Protin1 · Jean Le Grusse4 · Hélène Derumeaux5 · Peggy Gandia6 · Fatemeh Nourhashemi7,9 · Laurent Sailler8 · Agnès Sommet2,9 · Pierre Delobel1,10 · Guillaume Martin‑Blondel1,10 Accepted: 17 October 2020 © Springer Nature Switzerland AG 2020
Abstract Objectives Pyrazinamide (PZA) has a controversial safety profile in older patients. We aimed to assess the frequency and risk factors for adverse drug reactions (ADRs) in patients over 75 years of age treated for tuberculosis with or without PZA. Methods We conducted a retrospective monocentric study including patients aged over 75 years treated for active tuberculosis between 2008 and 2018. The frequency, type, seriousness, and causality assessment of ADRs to anti-tuberculosis treatment were compared between patients receiving PZA or not. Risk factors for ADRs were investigated using univariable and multivariable analyses by logistic regression. Results Among the 110 patients included, 54 (49.1%) received PZA (group 1) and 56 (50.9%) did not (group 2). ADRs to anti-tuberculosis drugs occurred in 31 patients (57.4%) in groups 1 and 15 (26.8%) in group 2 (p = 0.003). PZA-related ADRs occurred in 40.7% of exposed patients. Frequency of renal ADRs was higher in group 1 (9.3% vs 0%; p = 0.026). Rates of hepatic (18.5% vs 12.5%; p = 0.38), digestive (22.2% vs 8.9%; p = 0.054), and allergic (14.8% vs 5.4%; p = 0.12) ADRs were numerically higher in group 1 although the differences were not statistically significant. Serious ADRs occurred more frequently in group 1 (24.1% vs 8.9%; p = 0.03). The use of PZA was the only independent risk factor for ADRs to anti-tuberculosis drugs (odds ratio 3.75, 95% CI 1.5–9.6; p = 0.0056). No risk factors for PZA-related ADRs were identified. Conclusion In older French patients, the use of PZA was associated with more frequent ADRs to anti-tuberculosis drugs. Key Points Older patients are more vulnerable to adverse drug reactions (ADRs) to anti-tuberculosis treatments. Serious ADRs were significantly more frequent in older patients treated for tuberculosis with regimens including pyrazinamide. The risk–benefit ratio of using pyrazinamide to treat active tuberculosis should be considered with caution in older patients.
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s40266-020-00811-9) contains supplementary material, which is available to authorized users. * Stella Rousset rousset.st@chu‑toulouse.fr Extended author information available on the last page of the article
1 Introduction Tuberculosis in the elderly has become a global health problem in high income settings, as the geriatric population represents a large reservoir of tuberculosis infection [1]. Tuberculosis is frequently encountered in the elderly because of the reactivation of latent tuberc
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