P677 Azathioprine dosing and metabolite measurement in paediatric inflammatory bowel disease—does one size fit all?

Abstract

Azathioprine (AZA) is an effective immunomodulatory maintenance therapy in children with inflammatory bowel disease (IBD). Current recommended dosing is 2–2.5 mg/kg/dose in the presence of normal thiopurine methyltransferase (TPMT) level. Elevated levels of the AZA metabolites 6-TGN and 6-MMP have been associated with increased risk of myelotoxicity and hepatotoxicity, however evidence suggests that monitoring metabolites can help optimise effectiveness and safety of thiopurines. We aim to assess association between AZA weight-based dosing, thiopurine metabolites and disease activity index in a cohort of paediatric IBD patients. Retrospective data review (2015–2017) from the paediatric gastroenterology department at Evelina London Children’s Hospital. Children with IBD who were taking AZA and had regular thiopurine metabolites measurement were included. PCDAI and PUCAI were used to assess disease activity. A total of 41 patients, 38% female, 62% male with mean (±SD) age of diagnosis 12.2 (±3.4) years, were included. Twelve patients had ulcerative colitis (UC), 27 Crohn’s disease (CD) and 2 very early onset IBD (VEOIBD). Mean AZA dose, in mg/kg (±SD), 1.3 (±0.08). Mean 6TGN value (±SEM) 260 (±25.2), and mean MMT value (±SEM) 1023 (±168). Thiopurine metabolites were measured at (mean ± SEM) after (75 ± 13.5) days after starting AZA, 5 patients had elevated 6TGN levels >450. Mean lymphocyte count at time of metabolite measurement (±SD) 1.7 (±0.8). Activity index at the start of thiopurine were (±SD) 22.5 (±16.3) and when metabolites were measured 8.1 (±12). We have identified that the majority of our patients maintain clinical remission (defined by an activity index—PUCAI/PCDAI—of less than 10) on lower AZA doses than currently recommended. We have also identified a number of patients with elevated 6TGN levels without signs of myelosuppression. Higher doses of AZA are associated with higher metabolite levels, and we propose that regular routine measurement of AZA metabolites will help optimise therapy, minimise side effects and identify children at risk of hepato- and myelotoxicity.