Crohn's disease, ulcerative colitis, and indeterminate colitis are collectively termed inflammatory bowel disease (IBD). Corticosteroids remain the predominant therapy for acute exacerbation of IBD. However, many patients require short or long-term corticosteroid therapy, which can result in substantial side effects. In pediatrics, these concerns focus mainly on linear growth and vertebral compression fractures since IBD patients are more susceptible to them as a consequence of their disease. Therefore, there is an interest in alternative methods of treatment. The immunomodulatory agents, azathioprine and 6-mercaptopurine, have been used for over 20 years to decrease or eliminate long term steroid exposure. However, they have one serious clinical fault: their time course for efficacy peaks at 3-6 months after the initiation of oral therapy. Since patients requiring immunomodulatory agents are significantly ill, this delay is a substantial drawback for their use as a therapeutic agent. Hypothesis & Aims: The intravenous loading of azathioprine followed by oral dosing will result in its earlier onset of action and will prove to be an effective, yet timely therapeutic option in inflammatory bowel disease (IBD). We will study the effect of intravenous loading of azathioprine compared to placebo immediately prior to the initiation of oral azathioprine therapy. Methods: This is a prospective, randomized, double blind trial involving 48 subjects studied over a 12-month period. All enrolled subjects will have a baseline laboratory evaluation to identify eligibility for the study. These studies will be repeated immediately following the IV infusion, then weekly for 6 weeks, bi-weekly for the next 6 weeks, and then every two months until study completion. The subjects will receive the initiation of treatment in hospital. Using a random card/sealed envelope selection process performed by the CHOP pharmacist, the subject will receive either IV medicine or placebo depending on the card that is drawn. Analysis: The groups will be compared on all relevant baseline variables. Logarithmic analysis of the continuous variables will be made as needed with non-parametric statistics, T-tests, and the Mann-Whitney U tests. The log-rank test will be used to compare the time-to-response curves of the azathioprine IV group and the placebo IV group. Discussion: Unfortunately, there is no data concerning intravenous loading of immunomodulatory agents in children. There is also only limited data about the safety and efficacy of the immunomodulatory agents in children with IBD. It is anticipated that this therapy would significantly improve the time course of action in a safe manner in children, thereby limiting linear growth failure at a crucial time in the development of a child or adolescent through a steroid-sparing effect. Progress to date: Two patients with Crohn's disease have been enrolled and have completed at least 6 weeks of the trial. One patient is feeling very well and has no evidence of inflammation in his duodenum (initiating ulcer site). The other patient had a decrease in her ESR and her perianal fistula is now granulating/healing. The latter patient developed a mild URI for 2 weeks which resolved without changes in her medications or evidence of leukopenia.
Showing the most recent 10 out of 455 publications
