IBD Watch®
Timely Information for Practicing Physicians
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JUNE 2006 CROHN'S DISEASE (CD) Risk factors for initial surgery in a pediatric population. Gupta and others retrospectively reviewed clinical data from 989 consecutive pediatric patients with CD, aged 0 to 17 years at the time of diagnosis, who were followed at six centers between January 2000 and November 2003 to determine the risk factors for intestinal resection. Median follow-up time was 2.8 years (range, 1 day to 16.7 years) and 128 patients underwent intestinal resection. The Kaplan-Meier survival estimates of the cumulative incidence of surgery were 17% at 5 years and 28% at 10 years. Multivariate Cox regression models identified female gender (P = 0.03), initial diagnosis of ulcerative colitis (UC; P <0.0001), poor growth at presentation (P = 0.007), and the development of an abscess (P = 0.009), fistula (P = 0.0005), or stricture (P <0.0001) to be risk factors for surgery. Treatment with infliximab or 5-aminosalicylic acid (5-ASA) was associated with a decreased risk for surgery. Recognition of these risk factors may help guide therapy and decrease the need for surgery. (Gupta N, et al. Gastroenterology. 2006;130:1069–1077.) Infliximab plus azathioprine (AZA)/6-mercaptopurine (MP). Lemann and associates randomized 113 patients who had active CD despite more than 6 months of prednisone therapy to receive AZA or 6-MP plus infliximab 5 mg/kg or placebo on study weeks 0, 2, and 6. They were stratified as having or not having received a stable dose of AZA or 6-MP for >6 months. The primary end point was remission off steroids at week 24. At week 24 the success rate was higher in the infliximab group than in the placebo group (57% vs 29%; P = 0.003) for patients in both strata. These data show that infliximab plus AZA or 6-MP is more effective than AZA or 6-MP alone in patients with steroid-dependent CD. (Lemann M, et al. Gastroenterology. 2006;130:1354–1357.) Editor’s note: 1- to 2-year data will be more relevant, as prior studies have suggested a response to azathioprine of >40% at 12 to 15 months.
INFLAMMATORY BOWEL DISEASE (IBD) 6-Thioguanine nucleotide (6-TGN) levels. Previous studies have reported conflicting results regarding the correlation of 6-TGN serum levels with IBD activity. These findings led Osterman and colleagues to conduct a meta-analysis of studies undertaken between 1966 and November 2004 and identified by a Medline and PubMed search. Twelve articles were found that contained sufficient data for analysis. The mean/median 6-TGN levels were higher among patients in remission than among patients with active IBD (P = 0.006). Although the results were heterogeneous, patients with 6-TGN levels above a threshold of 230 to 260 pmol/8 × 108 red blood cells were more likely to be in remission than were patients with lower 6-TGN levels (62% vs 36%; P <0.001). In a second study of 126 patients with IBD, Hande and coworkers found that 5-ASA therapy was associated with higher 6-TGN levels, presumably through the inhibition of thiopurine methyltransferase (TPMT). CD and TPMT heterozygosity were independently associated with higher 6-TGN levels. However, 5-ASA was not associated with a change in 6-MP levels. (Osterman MT, et al. Gastroenterology. 2006;130:1047–1053; Hande S, et al. Inflamm Bowel Dis. 2006;12:251–257.)
Pediatric intermediate colitis (IC). Carvalho and others retrospectively analyzed clinical data from all children diagnosed with IBD at the Johns Hopkins Children's IBD Center between 1996 and 2001. A total of 250 children were registered in their database; of these, 127 (50.8%) had a diagnosis of UC, 49 (19.6%) had CD, and 74 (29.6%) had IC. Patients with IC were younger at diagnosis than were patients with CD (P <0.001). Among patients with IC, 59 (79.7%) had pancolitis at diagnosis and 15 (20.3%) had left-sided disease that progressed to pancolitis within a mean of 6 years. Approximately one third of the patients with IC (n = 25) were reclassified as having CD or UC after a median of 1.9 years (range, 0.6 to 4.5 years). The authors concluded that IC is a distinct pediatric subgroup of IBD. Further studies are needed to determine the long-term implications for patients initially diagnosed with IC. (Carvalho R, et al. Inflamm Bowel Dis. 2006;12:258–262.)
Ineffective biologics. Herrlinger and associates conducted a study in which 51 patients with mild to moderate CD were randomized to receive subcutaneous recombinant human interleukin-11 (rhIL-11) 1 mg/wk, prednisolone 60 mg/day with a taper after 1 week, or placebo, for 12 weeks. Remissions were induced in 14% of rhIL-11–treated patients and 50% of prednisolone-treated patients at week 6 (P <0.05). Commonly observed side effects in the rhIL-11 group included rash (n = 4), fever (n = 3), arthralgia/arthritis (n = 3), and nausea/vomiting (n = 3). This study showed that rhIL-11 was inferior to prednisolone as induction therapy for patients with active CD. In a second study, van Assche and others randomized 159 patients with moderately active UC to receive daclizumab (a humanized monoclonal antibody directed against the interleukin-2 receptor) 1 mg/kg intravenously at weeks 0 and 4, or 2 mg/kg at weeks 0, 2, 4, and 6, or placebo. At week 8, 2%, 7%, and 10% of patients in the daclizumab 1 and 2 mg/kg and placebo groups, respectively, achieved remission. These results indicate that daclizumab is not an effective therapy for patients with moderately active UC. (Herrlinger KR, et al. Am J Gastroenterol. 2006;101:793–797; van Assche G, et al. Gut 2006 Apr 7 [Epub ahead of print].)
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