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Association between Leflunomide and Pulmonary Hypertension
Thomas Lacoste-Palasset1,2,3, Marie-Camille Chaumais3,4,5, Jason Weatherald6
1Service de Pneumologie, Centre de Référence de l'Hypertension Pulmonaire, and.
Annals of the American Thoracic Society
|January 27, 2021
Summary
Leflunomide is rarely associated with pulmonary hypertension (PH), often alongside other risk factors. Pharmacovigilance and lab studies suggest a link between leflunomide and PH development.
Area of Science:
- Pharmacology
- Pulmonology
- Toxicology
Background:
- Pulmonary hypertension (PH) has been anecdotally linked to leflunomide treatment.
- Assessing this association is crucial for patient safety and drug monitoring.
Purpose of the Study:
- To evaluate the association between leflunomide and the development of pulmonary hypertension.
- To investigate the underlying mechanisms of leflunomide-induced PH.
Main Methods:
- Retrospective analysis of PH cases from French registries and pharmacovigilance databases (1999-2019).
- Review of clinical, functional, and hemodynamic data; pharmacovigilance disproportionality analysis.
- In vitro investigation of leflunomide's effect on human pulmonary endothelial cells.
Main Results:
- Twenty-eight leflunomide-treated patients with PH were identified; 75% had other PH risk factors.
- Median time to PH diagnosis was 32 months; precapillary PH was confirmed hemodynamically.
- Pharmacovigilance data showed significant leflunomide overrepresentation in pulmonary arterial hypertension reports; in vitro studies confirmed leflunomide toxicity.
Conclusions:
- PH associated with leflunomide is uncommon and frequently co-occurs with other risk factors.
- Pharmacovigilance and experimental findings support a causal association between leflunomide and PH.
- This highlights the need for vigilance in patients on leflunomide therapy.
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