Colesevelam for the treatment of bile acid malabsorption-associated diarrhea in patients with Crohn's disease: A randomized, double-blind, placebo-controlled study

Background and Aims: Bile acid malabsorption (BAM)-associated diarrhea is an important clinical issue in patients with Crohn's disease (CD). We analyzed the efficacy and safety of the bile acid sequestrant colesevelam for treatment of BAM-associated diarrhea in CD patients in a randomized, double-blind, placebo-controlled study. Methods: The primary endpoint was the proportion of patients with >30% reduction of liquid stools/day from baseline to termination visit at week 4. Secondary endpoints were reduction of the number of liquid stools/day, improvement of stool consistency and quality of life. Results: 26 patients were analyzed in the intention-to-treat (ITT) analysis. The primary endpoint was reached by 10 patients (69.7%) in the colesevelam group compared to 3 patients (27.3%) in the placebo group (risk difference RD = .394, 95%CI: [-0.012; 0.706]; P = .0566). In the per-protocol analysis (n = 22), the risk difference was statistically significant (RD = .470, 95%CI: [0.018; 0.788], P(H-0: RD = 0) = 0.0364; 95% CI: [1.3; 54.7]). Regarding secondary endpoints, in the ITT population colesevelam-treated patients had a significant reduction of liquid stools/day at week 4 (median 5.0 to 2.0; P = 0.01), while patients treated with placebo had no significant reduction (median 4.0 to 3.0; P = 0.42). Significantly more patients in the colesevelam group had improvement of stool consistency of at least one level in the Bristol stool chart, as compared to the placebo group (P = 0.003). Conclusions: We found significant differences in favor for colesevelam treatment compared to placebo treatment for CD patients with BAM regarding the reduction of the number of liquid stools/day and stool consistency. (C) 2014 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.