Therapeutic drug monitoring (TDM) of Leflunomide as an immunosuppressive treatment in thoracic (cardiac and/or lung) transplant recipients at The Georges POMPIDOU European Hospital-Paris-France

Leflunomide is an immunosuppressant indicated in the treatment of rheumatoid arthritis. This drug has a particular pharmacokinetics. Therapeutic Drug Monitoring (TDM) has been recommended for this drug because of its hepatic and hematological toxicities. We present here the prospective and retrospective analysis of a preliminary experience of the use of leflunomide as an alternative immunosuppressant in heart and/or lung transplantation of patients with or without cystic fibrosis. This study was conducted in 17 heart transplant patients (n=8) and/or lung transplant patients (n=9, 7 of whom had cystic fibrosis) who received treatment with leflunomide between April 2005 and June 2008. The indication for leflunomide was generally intolerance to the other immunosuppressants. The residual concentrations measured in patients with cystic fibrosis (C₀ = 12.8 ± 5.5 mg/L) were statistically lower than those measured in patients without cystic fibrosis (C₀ = 44.0 ± 24.2 mg/L) (p < 0.05). However, the dose related to weight in patients with cystic fibrosis (D = 0.32 ± 0.08 mg/Kg) tends to be slightly higher than that in patients without cystic fibrosis (D = 0.26 ± 0.10 mg/Kg). In terms of evolution, two patients died, one patient was lost to follow-up and leflunomide was stopped in 2 patients. With a mean follow-up of 12 months, the outcome was acceptable in the 12 patients in whom treatment was maintained. This experience must be evaluated over the longer term so that it can be extended to a larger cohort or proposed earlier after transplantation.