IBD Watch^®

^{Timely Information for Practicing Physicians}

MARCH 2007

Maintenance therapy with adalimumab. Colombel and others reported the results of a study of the efficacy and safety of adalimumab in the maintenance of response and remission in patients with moderate to severe Crohn’s disease (CD). All patients received induction therapy with adalimumab, 80 mg subcutaneously (week 0) followed by 40 mg at week 2. At week 4, responding patients (those demonstrating a decrease in the CD Activity Index of ≥70 points) were randomized to double-blind treatment with adalimumab, 40 mg weekly, 40 mg every other week (EOW), or placebo, through week 56. The percentage of responders in remission was greater in the adalimumab weekly and EOW groups than in the placebo group at weeks 26 (47%, 40%, and 17%, respectively; P <0.001) and 52 (41%, 36%, and 12%, respectively; P <0.001). There was no significant difference between the two adalimumab groups. In addition, more patients treated with placebo discontinued treatment due to an adverse event than those receiving adalimumab weekly or EOW (13.4% vs 4.7% vs 6.9%). These results show that continued adalimumab therapy is effective in maintaining remission in patients with moderate to severe CD through 56 weeks and is well tolerated. (Colombel J-F, et al. Gastroenterology. 2007;132:52–65.) 

Survival after colorectal cancer (CRC). While patients with CD are at an increased risk of CRC, little is known about the impact of CD on CRC prognosis. Larsen and associates investigated data from the Danish Cancer Registry and Danish Hospital Discharge Registry to compare survival rates among patients with CRC who did and did not have CD between 1977 and 1999. They identified 100 patients with CRC and CD and 71,438 patients with CRC but no CD. At the diagnosis of CRC, patients with CD were younger; however, CRC stage distributions were similar between the two groups. At 1 and 5 years the hazard ratios were 1.82 (95% confidence interval [CI], 1.36 to 2.43) and 1.57 (95% CI, 1.24 to 1.99]), respectively, in the patients with CD compared with the patients without CD. Additionally, the impact of CD on survival was more pronounced in younger patients (≤59 years of age), men, and patients with regional tumor spread. These data indicate that CD worsens the prognosis of CRC. (Larsen M, et al. Am J Gastroenterol. 2007;102:163–167.) 

High concentration multimatrix system (MMX) mesalamine. MMX mesalamine is a once-daily, high-strength (1.2 g/ tablet) formulation of mesalamine designed to deliver the drug throughout the colon. Kamm and co-workers conducted a double-blind, multicenter study in which 343 patients with active mild-to-moderate ulcerative colitis (UC) were randomized to receive MMX mesalamine, 2.4 g/day, MMX mesalamine, 4.8 g/day, delayed-release oral mesalamine, 2.4 g/day in three divided doses, or placebo, for 8 weeks. Compared with placebo, MMX mesalamine, 2.4 and 4.8 g/day, was associated with clinical and endoscopic remission at week 8 in greater percentages of patients (21% vs 40.5% vs 41.2%). No significant differences were observed between the delayed-release mesalamine and placebo treatment arms. These results show that MMX mesalamine is an effective and convenient therapy for patients with mild-to-moderate UC. (Kamm MA, et al. Gastroenterology. 2007;132:66–75.) 

Response to corticosteroids. Turner and others reviewed 32 cohort and controlled studies reporting short-term colectomy rates in patients who had severe UC or identified variables predictive of treatment failure. In the pooled analysis, 581 of 1,991 patients required colectomy and 22 patients died. A heterogeneity-controlled meta-regression analysis showed that the colectomy rate did not change over the last 30 years. A second meta-regression analysis failed to show a dose-colectomy response for methylprednisolone beyond 60 mg/day (P = 0.98). The following variables were found to consistently predict medical therapy failure: disease extent, stool frequency, temperature, heart rate, C-reactive protein, albumin, and radiologic assessment. These data do not support the use of methylprednisolone at dosages of >60 mg/day. The variables that predict outcomes of corticosteroid therapy could be used to develop guidelines for the use of rescue therapies. (Turner D, et al. Clin Gastroenterol Hepatol. 2007;5:103–110.) Editor’s note: The authors failed to note the placebo-controlled trial of cyclosporine in patients with severe UC by Lichtiger et al (N Engl J Med 1994;330:1841–1845), which showed an 82% acute response rate that was confirmed by van Assche et al in a randomized, double-blind, dose comparison study showing 85% acute response. In 1996, Travis, in Gut, demonstrated similar predictors of response to cyclosporine and steroids.—S.H. 

Efficacy and safety of thalidomide. Lazzerini and colleagues studied the long-term efficacy and safety of thalidomide in 28 children and young adults with refractory IBD (19 with CD, 9 with UC). Patients received oral thalidomide, 1.5 to 2.5 mg/kg per day and were assessed at baseline and weeks, 2, 4, 8, and 12, then every 12 weeks thereafter. Remission was achieved in 21 (75%) of the 28 patients (17 with CD, 4 with UC). The mean duration of remission was 34.5 months, and 16 (80%) of 20 patients were able to discontinue steroid use. Reversible neuropathy occurred after cumulative doses of thalidomide, >28 g, in 7 (25%) of the 28 patients. Other side effects included somnolence/vertigo (n = 1) and hallucinations/agitation (n = 1). This study indicates that thalidomide treatment induces long-term remissions in children and adolescents with intractable IBD. Neuropathy, the most common dose-limiting toxicity, was cumulative and dose-dependent, allowing for long-term remission before drug suspension. (Lazzerine M, et al. Aliment Pharmacol Ther . 2007;25:419–427.)

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