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Safety of Pyrazinamide for the Treatment of Tuberculosis in Older Patients Over 75 Years of Age: A Retrospective Monocentric Cohort Study

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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.

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Acknowledgements

We warmly thank Mrs. Colleen Beck (Department of Infectious and Tropical Diseases, Toulouse University Hospital) for her proofreading. Preliminary results were previously presented as an abstract in the ECCMID 2020 congress abstract book in April 2020, and as a poster at the Journées Nationales d’Infectiologie (JNI) in September 2020 in Poitiers, France.

Author information

Authors and Affiliations

  1. Department of Infectious and Tropical Diseases, Toulouse University Hospital, Place du Docteur Baylac, TSA 40031, 31059, Toulouse Cedex 9, France

    Stella Rousset, Caroline Protin, Pierre Delobel & Guillaume Martin-Blondel

  2. Clinical Pharmacology Department, Toulouse University Hospital, 37 Allées Jules Guesde, 31073, Toulouse Cedex, France

    Margaux Lafaurie & Agnès Sommet

  3. Department of Bacteriology, Toulouse University Hospital, 330 Avenue de Grande-Bretagne; TSA 40031, 31059, Toulouse Cedex 9, France

    Hélène Guet-Revillet

  4. Tuberculosis Control Centre, Joseph Ducuing Hospital, 15 Rue de Varsovie, BP 53160, 31027, Toulouse Cedex 3, France

    Jean Le Grusse

  5. Medical Information Department, Toulouse University Hospital, Place du Docteur Baylac, TSA 40031, 31059, Toulouse Cedex 9, France

    Hélène Derumeaux

  6. Clinical Pharmacokinetics Laboratory, Toulouse University Hospital, Place du Docteur Baylac, TSA 40031, 31059, Toulouse Cedex 9, France

    Peggy Gandia

  7. Department of Geriatrics, Toulouse University Hospital, Place Lange, TSA 60033, 31059, Toulouse Cedex 9, France

    Fatemeh Nourhashemi

  8. Department of Internal Medicine, Place du Docteur Baylac, Toulouse University Hospital, TSA 40031, 31059, Toulouse cedex 9, France

    Laurent Sailler

  9. INSERM UMR 1027, University of Toulouse III, 37 Allées Jules Guesde, 31000, Toulouse, France

    Margaux Lafaurie, Fatemeh Nourhashemi & Agnès Sommet

  10. INSERM U1043, CNRS UMR 5282, Centre de Physiopathologie Toulouse-Purpan, Place du Docteur Baylac, TSA 40031, 31059, Toulouse Cedex 9, France

    Pierre Delobel & Guillaume Martin-Blondel

Authors
  1. Stella Rousset
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  2. Margaux Lafaurie
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  8. Fatemeh Nourhashemi
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  12. Guillaume Martin-Blondel
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Corresponding author

Correspondence to Stella Rousset.

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Funding

This study was not supported by any external funding.

Conflict of Interest

Stella Rousset, Margaux Lafaurie, Hélène Guet-Revillet, Caroline Protin, Jean Le Grusse, Hélène Derumeaux, Peggy Gandia, Fatemeh Nourhashemi, Laurent Sailler, Agnès Sommet, Pierre Delobel, and Guillaume Martin-Blondel declare that they have no conflict of interest.

Ethics Approval

This retrospective monocentric cohort study was approved by an institutional review board (RnIPH number 2020-51), in accordance with the French data protection authority (MR004, Commission Nationale de l’Informatique et des Libertés, CNIL number 2206723v0). Consultation of an Ethics Committee was not required as this was a non-interventional study that does not fall under the French Jardé law.

Consent to Participate and for Publication

According to French law on ethics, patients were informed that their codified data will be used for the study and for publication. Their non-opposition to the use of the data and to publication was collected.

Availability of Data and Material

Data are available upon reasonable request to Professor Guillaume Martin-Blondel.

Code Availability

Not applicable.

Author Contributions

Conceptualization: SR, GM-B, and PD; Methodology: SR, ML, AS, and GM-B; Software: SR; Investigation: SR, ML, HG-R, and HD; Data curation: SR; Writing–Original Draft: SR and GM-B; Writing–Review and editing: ML, HG-R, CP, JLG, PG, FN, LS, AS, and PD; Visualization: SR; Supervision: GM-B; Project administration: SR and GM-B.

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Rousset, S., Lafaurie, M., Guet-Revillet, H. et al. Safety of Pyrazinamide for the Treatment of Tuberculosis in Older Patients Over 75 Years of Age: A Retrospective Monocentric Cohort Study. Drugs Aging 38, 43–52 (2021). https://doi.org/10.1007/s40266-020-00811-9

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