Suivi thérapeutique pharmacologique des 6-thioguanine nucléotides dans les maladies inflammatoires cryptogéniques de l'intestin : intérêt et limites

Abstract

Azathioprine, 6-mercaptopurine, and 6-thioguanine are immunosuppressive drugs indicated in the prevention of graft rejection, and treatment of auto-immune disease or inflammatory bowel disease. Their anti-nucleotidic properties are also used for the treatment of acute leukaemia. Their metabolism involves thiopurine methyl transferase, which activity varies according to genetic polymorphisms. In inflammatory bowel disease patients, there is no recommended therapeutic range of intra-erythrocyte 6-thioguanine nucleotide concentration, the active metabolite. Therapeutic drug monitoring of 6-thioguanine nucleotide concentrations is however proposed in the following clinical situations: to check the observance, to try to explain therapeutic failure, to manage patients with limited thiopurine methyl transferase activity or patients treated with associated drugs that can modify thiopurine methyl transferase activity. The literature review shows that high concentrations of 6-thioguanine nucleotides and methylated metabolites are associated with an increased risk of bone marrow toxicity. In addition, high concentrations of methylated metabolite might increase the risk of hepatic toxicity. These major side-effects can be prevented by the use of pre-treatment screening for thiopurine methyl transferase activity or genotype in inflammatory bowel disease patients in order to propose an adapted dosing.

Keywords: 6-thioguanine nucleotides; 6-thioguanine nucléotides; suivi thérapeutique pharmacologique; therapeutic drug monitoring.