ITPA Activity in Children treated by Azathioprine: Relationship to the Occurrence of Adverse Drug Reactions and Inflammatory Response.

ITPA Activity in Children treated by Azathioprine: Relationship to the Occurrence of Adverse Drug Reactions and Inflammatory Response.

Basic Clin Pharmacol Toxicol. 2018 Jan 11;:

Authors: Citterio-Quentin A, Moulsma M, Gustin MP, Lachaux A, Boulieu R

Abstract
Azathioprine (AZA), a thiopurine drug, is widely used in the treatment of children with immunological disease such as inflammatory bowel disease (IBD) and autoimmune hepatitis (AIH); however, interindividual variability in the occurrence of adverse drug reaction (ADRs) and drug response is observed. This study investigated 1) the relationships between inosine triphosphate pyrophosphatase (ITPA) activity, an enzyme involved in thiopurine metabolism, and the occurrence of ADRs in children with immunological disease on AZA therapy, 2) the relationship between ITPA activity and the inflammatory activity observed in children with IBD. ITPA and TPMT activities were determined in 106 children with immunological disease on AZA therapy. Markers of hepatotoxicity, myelotoxicity, pancreatitis and inflammation as well as clinical information were retrospectively collected during regular medical visits. No significant association was found between ITPA activity and hepatotoxicity or clinical ADRs such as cutaneous reactions, arthralgia, flu-like symptoms and gastrointestinal disorders. Concerning myelotoxicity, a significant relation was observed between ITPA activity and RBC mean corpuscular volume (MCV) (P=0.003). This observation may be related to the significant relationship found between high ITPA activity and the increase of gamma globulin level reflecting inflammation (P=0.005). In our study, ITPA activity was not associated with occurrence of ADRs but a relationship between high ITPA activity and gamma globulin, a marker of inflammation, was found in children with IBD. Thereby, measurement of ITPA activity may help to identify IBD children predisposed to residual inflammation on AZA therapy. Further prospective studies are needed to confirm this result. This article is protected by copyright. All rights reserved.

PMID: 29327413 [PubMed - as supplied by publisher]

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