IBD Watch^®

^{Timely Information for Practicing Physicians}

 FEBRUARY 2006

ULCERATIVE COLITIS (UC)

Infliximab therapy. Infliximab is a chimeric monoclonal antibody directed against tumor necrosis factor–α that has become an established therapy in patients with Crohn's disease. Rutgeerts and colleagues report the results of two double-blind trials (Active Ulcerative Colitis Trials [ACT] 1 and 2) in each of which 364 patients with moderate-to-severe active UC despite standard treatments were randomized to receive infliximab 5 or 10 mg/kg or placebo at weeks 0, 2, 6, and every 8 weeks thereafter to week 46 in ACT 1 or week 22 in ACT 2. Patients were followed for 54 weeks in ACT 1 and 30 weeks in ACT 2. Mucosal healing at weeks 8 and 30 in each study and at week 54 in ACT 1 occurred in a greater proportion of patients in the infliximab groups than in the placebo groups (P £0.009 for all comparisons). In addition, the proportions of patients who discontinued corticosteroids at week 30 in both studies and at week 54 in ACT 1 were consistently higher in the infliximab groups than in the placebo groups. A clinical response was defined as a decrease in the Mayo score of ≥3 points and ≥30% with a decrease in the rectal bleeding subscore of ≥1 point or an absolute rectal bleeding subscore of 0 or 1. In both studies a greater percentage of infliximab-treated patients than controls achieved a clinical response (P <0.001). Further, in both studies a greater proportion of infliximab-treated patients than controls demonstrated a clinical response at week 30 (P ≤0.002) and in ACT 1 the clinical response rate at 54 weeks was greater in the infliximab-treated group than in the placebo group (P <0.001). These results demonstrate that infliximab is an effective induction and maintenance therapy for patients with moderate-to-severe UC. (Rutgeerts P, et al. N Engl J Med 2005;353:2462–2476.)

Azathioprine vs 5-aminosalicylic acid. There are limited evidence-based data to support the use of azathioprine in patients with ulcerative colitis. Ardizzone and co-workers conducted an investigator-blinded study in which 72 patients with steroid-dependent UC were randomized to receive azathioprine 2 mg/kg per day or 5-aminosalicylic acid 3.2 g/day for 6 months. All patients had clinically and endoscopically active disease at study entry and all patients were taking prednisolone 40 mg/day. A greater percentage of patients in the azathioprine treatment group than in the 5-aminosalicylic acid treatment group had clinical and endoscopic remission and discontinued prednisolone therapy (55% vs 21%; odds ratio [OR], 4.78 [95% confidence interval (CI), 1.57 to 14.5]). These findings suggest that azathioprine is a more effective therapy than 5-aminosalicylic acid for inducing clinical and endoscopic remission and allowing the discontinuation of steroid therapy in patients with steroid-dependent UC. (Ardizzone S, et al. Gut 2006;55:47–53.)

CROHN'S DISEASE (CD)

Corticosteroid therapy increases the risk for intra-abdominal or pelvic abscess. Systemic corticosteroid therapy increases the risk of postoperative sepsis in CD. Agrawal and others performed a retrospective case-control study of 432 patients with CD to investigate the effects of corticosteroid therapy on risk for sepsis in non-operated patients. Corticosteroid therapy was found to be associated with an increased risk for intra-abdominal or pelvic abscess in patients with perforating CD (OR, 9.03 [95% CI, 2.40 to 33.98]) and in patients with relapsed active CD (OR, 9.31 [95% CI, 1.03 to 83.91]). In addition, patients receiving prednisone ≥20 mg/day were at greater risk for developing an abscess than were patients taking lower prednisolone doses (OR, 2.81 [95% CI, 0.99 to 7.99]). Neither smoking nor azathioprine use was associated with increased risk for abscess. These data show that systemic corticosteroid therapy is associated with an increased risk for intra-abdominal or pelvic abscess in patients with CD. (Agrawal A, et al. Clin Gastroenterol Hepatol 2005;3:1215–1220.)

Role of organic cation transporter (OCTN) gene polymorphism. Recent data suggest that polymorphisms in the OCTN genes are disease-causing mutations within the IBD5 locus located on chromosome 5q31. Two recent studies have examined the association of OCTN variants with the risk of developing CD. In the first study, Vermeire and associates genotyped 2032 individuals, including 981 patients with inflammatory bowel disease (IBD), for disease-associated OCTN and DLG5 variants. The OCTN risk haplotype was associated with perianal penetrating CD (P = 0.035). No association with disease phenotype was found for DLG5. Neither OCTN nor DLG5 was associated with an increased susceptibility for IBD. In the second study, Noble and others investigated 374 patients with CD, 305 patients with UC, and 294 healthy controls. They found that the IBD5 locus influences susceptibility for CD as well as the clinical severity of CD. The contribution of OCTN variants was not independent of the IBD5 haplotype. A causative role for the OCTN genes was not proven and further genetic data are needed. (Vermeire S, et al. Gastroenterology 2005;129:1845–1853; Noble CL, et al. Gastroenterology 2005;129:1854–1864.)

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