Safety of Pyrazinamide for the Treatment of Tuberculosis in Older Patients Over 75 Years of Age

A Retrospective Monocentric Cohort Study

Stella Rousset (1) , Margaux Lafaurie (2, 3) , Hélène Guet-Revillet (4) , Caroline Protin (1) , Jean Le Grusse (5, 6) , Hélène Derumeaux (4) , Peggy Gandia (7) , Fatemeh Nourhashemi (4, 8) , Laurent Sailler (4) , Agnés Sommet (3, 2) , Pierre Delobel (1, 9) , Guillaume Martin-Blondel (1, 9)

1 Service Maladies infectieuses et tropicales [CHU Toulouse]
2 Service Pharmacologie Clinique [CHU Toulouse]
3 LEASP - Epidémiologie et analyses en santé publique : risques, maladies chroniques et handicaps
4 CHU Toulouse - Centre Hospitalier Universitaire de Toulouse
5 HJD - Hôpital Joseph Ducuing - Varsovie [Toulouse]
6 Tuberculose et biologie des infections [IPBS, Toulouse]
7 Laboratoire Pharmacocinétique et de Toxicologie [CHU Toulouse]
8 Equipe Vieillissement (CERPOP)
9 CPTP - Centre de Physiopathologie Toulouse Purpan

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.

Domaines: Maladies infectieuses

Stella Rousset, Margaux Lafaurie, Hélène Guet-Revillet, Caroline Protin, Jean Le Grusse, et al.. Safety of Pyrazinamide for the Treatment of Tuberculosis in Older Patients Over 75 Years of Age. Drugs and Aging, 2021, 38 (1), pp.43-52. ⟨10.1007/s40266-020-00811-9⟩. ⟨hal-03158686⟩