IBD Watch^®

 NOVEMBER  2006

Pediatric therapies for inflammatory bowel disease (IBD). Hyams and associates analyzed clinical outcomes data from 97 children aged <16 years with ulcerative colitis (UC) diagnosed between January 2002 and March 2005. Data were prospectively entered into the Pediatric Inflammatory Bowel Disease Collaborative Research Group Registry. Patients were managed according to the dictates of their respective physicians. After a minimum follow-up of 1 year, 79% of patients had received corticosteroids, and while the early response to this therapy was excellent, corticosteroid dependence was 45% at 1 year. In a second study, Markowitz and others described 3-month and 1-year outcomes of children with Crohn’s disease (CD) who were treated with corticosteroids within 30 days of diagnosis. Data from 109 children in this multicenter, observational study were analyzed. At 3 months, 84% of patients had responded to corticosteroids. However, at 1 year, 31% of patients were corticosteroid-dependent and 8% of patients had required surgery. Sixteen of 24 corticosteroid-dependent or -resistant patients rapidly discontinued corticosteroids after starting infliximab. Separately, Jaspers and coworkers retrospectively examined the use of azathioprine in 88 children with CD that was diagnosed between 1998 and 2003. All patients underwent ³18 months of follow-up. Maintenance azathioprine was given to 72 patients. The authors found that patients diagnosed after 2000 received azathioprine earlier in the course of their disease, and maintenance azathioprine was associated with prolonged first remissions following initial corticosteroid therapy. (Hyams J, et al. Clin Gastroenterol Hepatol. 2006;4:1118–1123; Markowitz J, et al. Clin Gastroenterol Hepatol. 2006;4:1124–1129; Jaspers GJ, et al. Inflamm Bowel Dis. 2006;12:831–836.)

Pharmacogenomic studies during thiopurine therapy. Hindorf and coworkers conducted pharmacogenomic studies in 60 consecutive patients with IBD who were given thiopurine. Thiopurine methyltransferase (TPMT) activity did not change during thiopurine treatment, but TPMT gene expression decreased. Patients with high methylthioinosine monophosphate concentrations early in the pharmacokinetic steady state phase were found to be at an increased risk of developing myelotoxicity. (Hindorf U, et al. Gut. 2006;55:1423–1431.)

Patient preferences influence ulcerative colitis (UC) treatment decisions. Arseneau and colleagues used a Markov model to assess the treatment outcome preferences of 48 patients with steroid-refractory UC. They found that patient preferences had a clear impact on the treatment selected. Averaged preferences supported the use of medical treatments over surgery. However, one third of patients may benefit most by proceeding directly to colectomy. The authors concluded that a failure to fully assess patient preferences may result in suboptimal treatment for individual patients. (Arseneau KO, et al. Clin Gastroenterol Hepatol. 2006;4:1135–1142.)

Multi Matrix System™ (MMX) mesalazine. MMX mesalazine is a high-strength (1.2 g/tablet) formulation that extends the delivery of mesalazine throughout the colon. D’Haens and others randomized 38 patients with mildly to moderately active UC to receive MMX mesalazine, 1.2, 2.4, or 4.8 g once daily for 8 weeks. The primary end point was remission, defined as a UC–Disease Activity Index (DAI) score of £1, a score of 0 for rectal bleeding and stool frequency, and a ≥1-point reduction in sigmoidoscopy score from baseline. At the completion of 8 weeks of treatment, remission rates were 0%, 31%, and 18% in the 1.2-, 2.4-, and 4.8-g/day treatment groups, respectively. In addition, the 2.4- and 4.8-g/day treatment groups demonstrated greater improvement in overall UC-DAI and component scores from baseline than did patients treated with MMX mesalazine, 1.2 g/day. MMX mesalazine was well tolerated. These data indicate that MMX mesalazine given as a 2.4- or 4.8-g/day regimen is effective treatment for patients with mildly to moderately active UC. (D’Haens G, et al. Aliment Pharmacol Ther. 2006;24:1087–1097.)

Infliximab therapy adherence in CD. Kane and Dixon evaluated adherence rates to intravenous infliximab in 274 patients with CD in the gastroenterology clinic at The University of Chicago from June 2002 to October 2003. There were only 48 (4%) “no show” appointments among 1,185 scheduled infliximab infusions. Six patients accounted for 13 (27%) of the missed appointments. Thirty-five patients missed only one appointment. Risk factors for “no show” appointments were female gender, the receipt of concomitant immunomodulator treatment, and having undergone the initial infliximab infusion >18 weeks earlier. Female patients and patients with Medicaid coverage were significantly more likely to miss more than one appointment than were other patients (P <0.05). These results demonstrate that nonadherence to scheduled infliximab therapy is low and that risk factors contributing to nonadherence include female gender and maintenance dosing of infliximab. (Kane S, Dixon L. Aliment Pharmacol Ther. 2006;24:1099–1103.)