Thiopurines in Pediatric Inflammatory Bowel Disease: Current and Future Place
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CURRENT OPINION
Thiopurines in Pediatric Inflammatory Bowel Disease: Current and Future Place Karen van Hoeve1,2 · Séverine Vermeire2,3
© Springer Nature Switzerland AG 2020
Abstract Thiopurines have been widely used to maintain steroid-free remission in children with inflammatory bowel disease (IBD). However, within the expanding treatment armamentarium, the role of these non-selective immunomodulators has been questioned, especially in pediatric patients, who often present with a more aggressive disease course, which can impact growth and development. The less favorable safety but also inferior efficacy profile associated with thiopurines, in contrast to the newer biological therapies, has interfered with their use. The future place of thiopurines in the management of childhood IBD, therefore, needs revisiting. This review provides a practical overview on the historical and current use of thiopurines in pediatric IBD with specific attention for thiopurine S-methyltransferase testing and monitoring of thiopurine metabolite levels as an approach to improve outcomes. We also give a personal expert opinion on the future role of these drugs in childhood IBD.
1 Introduction Inflammatory bowel diseases (IBDs) are characterized by chronic, relapsing inflammation of the gastro-intestinal tract. IBD is subclassified typically as Crohn’s disease (CD) and ulcerative colitis (UC), where inflammatory bowel disease type-unclassified (IBDU) is reserved for patients without specific features of either UC or CD, but features of both [1–3]. The exact etiology of IBD has not been fully elucidated yet [4–6]. Approximately 20–25% of newly diagnosed IBD patients present during childhood, with the highest peak of onset in adolescence (between 11 and 16 years of age) [7]. The incidence of pediatric IBD is still rising, with an incidence of 6.5–9.3 per 100,000 and 1.0–2.4 per 100,000 for CD and UC, respectively [8–12]. Despite all efforts, there is still no curative treatment [1, 2]. Due to the unclear pathogenesis, corticosteroids and * Séverine Vermeire [email protected] 1
Department of Pediatric Gastroenterology and Hepatology and Nutrition, University Hospitals Leuven, KU Leuven, Leuven, Belgium
2
TARGID, Department of Chronic Diseases and Metabolism (CHROMETA), KU Leuven, Leuven, Belgium
3
Department of Gastroenterology and Hepatology, University Hospitals Leuven, KU Leuven, Leuven, Belgium
Key Points Although thiopurines (azathioprine or 6-mercaptopurine) have been the principal immunosuppressive agents to treat inflammatory bowel disease in children for over half a century, they are slowly being replaced by newer biologicals. The rising concerns about the safety of thiopurines, with increased risk of malignancy and lymphoproliferative disorders, especially in children and young adults, and their inferior efficacy profile in comparison to infliximab have resulted in earlier introduction of biologicals, with treatment even skipping the use of thiopurines in the case of a top-down approach. Efforts hav
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