How are azathioprine and 6-mercaptopurine dosed by gastroenterologists? Results of a survey of clinical practice

Background: Azathioprine (AZA) and 6-mercaptopurine (6-MP) are accepted as effective therapy for Crohn's disease and ulcerative colitis. Although general guidelines have been suggested for weight-based dosing of thiopurines, no standard of care has been established. Clinical trials have demonstrated efficacy for weight-based dosing of AZA at 2.5 mg/kg/day and 6-MP at 1.5 mg/kg/day. Escalation of dosing is recommended within 2 weeks of initiating therapy. The aim was to determine the prescribing practices of community practice gastroenterologists with respect to 6-MP/AZA dosing. Methods: Questionnaires were distributed via a mail database or during gastroenterology society meetings to gastroenterologists in NY, NJ, and CT. Questionnaires ascertained starting doses of AZA/6-MP, use of thiopurine methyltransferase (TPMT) enzyme testing, and strategy for dose optimization. Results: A total of 145 questionnaires were collected. Twenty-four percent of gastroenterologists escalated the dose within 2 weeks after initiating therapy. The majority used weight-based dosing as their target of therapy. Thirty-five percent reported measuring TPMT levels and 46% used metabolite monitoring. Conclusions: Most gastroenterologists take longer than recommended to raise the dose of AZA/6-MP. Although the majority of gastroenterologists reported maximal dosages based on weight, there may be a delay in achieving this goal. Optimizing dosing of AZA/6-MP may improve efficacy and reduce the need to use additional therapy.