Stella Rousset1, Margaux Lafaurie2,3, Hélène Guet-Revillet4, Caroline Protin5, Jean Le Grusse6, Hélène Derumeaux7, Peggy Gandia8, Fatemeh Nourhashemi9,3, Laurent Sailler10, Agnès Sommet2,3, Pierre Delobel5,11, Guillaume Martin-Blondel5,11. 1. Department of Infectious and Tropical Diseases, Toulouse University Hospital, Place du Docteur Baylac, TSA 40031, 31059, Toulouse Cedex 9, France. rousset.st@chu-toulouse.fr. 2. Clinical Pharmacology Department, Toulouse University Hospital, 37 Allées Jules Guesde, 31073, Toulouse Cedex, France. 3. INSERM UMR 1027, University of Toulouse III, 37 Allées Jules Guesde, 31000, Toulouse, France. 4. Department of Bacteriology, Toulouse University Hospital, 330 Avenue de Grande-Bretagne; TSA 40031, 31059, Toulouse Cedex 9, France. 5. Department of Infectious and Tropical Diseases, Toulouse University Hospital, Place du Docteur Baylac, TSA 40031, 31059, Toulouse Cedex 9, France. 6. Tuberculosis Control Centre, Joseph Ducuing Hospital, 15 Rue de Varsovie, BP 53160, 31027, Toulouse Cedex 3, France. 7. Medical Information Department, Toulouse University Hospital, Place du Docteur Baylac, TSA 40031, 31059, Toulouse Cedex 9, France. 8. Clinical Pharmacokinetics Laboratory, Toulouse University Hospital, Place du Docteur Baylac, TSA 40031, 31059, Toulouse Cedex 9, France. 9. Department of Geriatrics, Toulouse University Hospital, Place Lange, TSA 60033, 31059, Toulouse Cedex 9, France. 10. Department of Internal Medicine, Place du Docteur Baylac, Toulouse University Hospital, TSA 40031, 31059, Toulouse cedex 9, France. 11. INSERM U1043, CNRS UMR 5282, Centre de Physiopathologie Toulouse-Purpan, Place du Docteur Baylac, TSA 40031, 31059, Toulouse Cedex 9, France.
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.
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.
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