Alimentary Pharmacology and Therapeutics Invited Editorials port its use in these patients. Furthermore, a recent randomised, double-blind, placebo-controlled study of colesevelam in patients with bile acid malabsorption after ileal resection for Crohn’s disease has shown significant improvements, with a reduction in the number of liquid stools and an improvement in stool consistency.5 Patients with a diagnosis of bile acid diarrhoea will be greatly benefitted from further well-designed studies with currently unlicensed drugs including colesevelam and other candidates. Increasing understanding of bile acid kinetics recognises the regulation of their synthesis by the farnesoid X receptor (FXR) – fibroblast growth factor 19 (FGF19) axis.6 In a condition that is characterised by increased faecal bile acid losses and hepatic overproduction, an alternative approach to increase FGF19 and decrease bile acid synthesis may eventually be shown to have value in many patients.1 However, colesevelam is currently available and is effective, and so should form an important part of the therapeutic armamentarium for bile acid malabsorption and diarrhoea.
ACKNOWLEDGEMENTS Declaration of personal interests: Julian Walters has served as a speaker, advisory board member or consultant for Albireo, GE Healthcare, Intercept Pharmaceuti-
Editorial: colesevelam effects on faecal bile acids in IBS with diarrhoea – author’s reply M. Camilleri Clinical Enteric Neuroscience Translational and Epidemiological Research (CENTER), Mayo Clinic, Rochester, MN, USA. E-mail: [email protected] doi:10.1111/apt.13111
The comments provided by Julian Walters and Richard Appleby1 regarding the recent Mayo Clinic study of the effects of colesevelam on faecal bile acids in IBS with diarrhoea are very much appreciated.2 In addition to their excellent comments, I wish to clarify for the readers that the increased bile acids in stool were sequestered and only released during the methanol extraction step; therefore, the increase in bile acids reaching the colon were biologically inactive, thereby reducing their diarrhoeagenic potential, as manifested by the improvement in stool consistency. Aliment Pharmacol Ther 2015; 41: 694–697 ª 2015 John Wiley & Sons Ltd
cals, NGM Biopharmaceuticals, Novartis, Pendopharm and Sanofi. Declaration of funding interests: Richard Appleby has been supported by research funding from Albireo and Intercept Pharmaceuticals.
REFERENCES 1. Wilcox C, Turner J, Green J. Systematic review: the management of chronic diarrhoea due to bile acid malabsorption. Aliment Pharmacol Ther 2014; 39: 923–39. 2. Camilleri M, Acosta A, Busciglio I, et al. Effect of colesevelam on faecal bile acids and bowel functions in diarrhoea-predominant irritable bowel syndrome. Aliment Pharmacol Ther 2015; 41: 438–48. 3. Wedlake L, A’Hern R, Thomas K, Walters JRF, Andreyev HJN. Systematic review: the prevalence of idiopathic bile acid malabsorption (I-BAM) as diagnosed by SeHCAT scanning in patients with diarrhoea-predominant irritable bowel syndrome (IBS). Aliment Pharmacol Ther 2009; 30: 707–17. 4. Camilleri M, Busciglio I, Acosta A, et al. Effect of increased bile acid synthesis or fecal excretion in irritable bowel syndromediarrhea. Am J Gastroenterol 2014; 109: 1621–30. 5. Beigel F, Teich N, Howaldt S, et al. Colesevelam for the treatment of bile acid malabsorption-associated diarrhea in patients with Crohn’s disease: a randomized, double-blind, placebo-controlled study. J Crohns Colitis 2014; 8: 1471–9. 6. Walters JR. Bile acid diarrhoea and FGF19: new views on diagnosis, pathogenesis and therapy. Nat Rev Gastroenterol Hepatol 2014; 11: 426–34.
The observed increase in serum C4 level, a surrogate for the rate of hepatic synthesis of bile acids, may compensate for the intraluminal sequestration by colesevelam of bile acids in the small intestine, and avoid aggravating the mild steatorrhoea observed in these patients with IBS-diarrhoea.3
ACKNOWLEDGEMENT The author’s declarations of personal and financial interests are unchanged from those in the original article.2 REFERENCES 1. Walters JRF, Appleby RN. Editorial: colesevelam effects on faecal bile acids in IBS with diarrhea. Aliment Pharmacol Ther 2015; 41: 696–7. 2. Camilleri M, Acosta A, Busciglio I, et al. Effect of colesevelam on faecal bile acids and bowel functions in diarrhoea-predominant irritable bowel syndrome. Aliment Pharmacol Ther 2015; 41: 438–48. 3. Camilleri M, Busciglio I, Acosta A, et al. Effect of increased bile acid synthesis or fecal excretion in irritable bowel syndromediarrhea. Am J Gastroenterol 2014; 109: 1621–30.
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ACKNOWLEDGEMENTS Declaration of personal interests: Julian Walters has served as a speaker, advisory board member or consultant for Albireo, GE Healthcare, Intercept Pharmaceuti-
Editorial: colesevelam effects on faecal bile acids in IBS with diarrhoea – author’s reply M. Camilleri Clinical Enteric Neuroscience Translational and Epidemiological Research (CENTER), Mayo Clinic, Rochester, MN, USA. E-mail: [email protected] doi:10.1111/apt.13111
The comments provided by Julian Walters and Richard Appleby1 regarding the recent Mayo Clinic study of the effects of colesevelam on faecal bile acids in IBS with diarrhoea are very much appreciated.2 In addition to their excellent comments, I wish to clarify for the readers that the increased bile acids in stool were sequestered and only released during the methanol extraction step; therefore, the increase in bile acids reaching the colon were biologically inactive, thereby reducing their diarrhoeagenic potential, as manifested by the improvement in stool consistency. Aliment Pharmacol Ther 2015; 41: 694–697 ª 2015 John Wiley & Sons Ltd
cals, NGM Biopharmaceuticals, Novartis, Pendopharm and Sanofi. Declaration of funding interests: Richard Appleby has been supported by research funding from Albireo and Intercept Pharmaceuticals.
REFERENCES 1. Wilcox C, Turner J, Green J. Systematic review: the management of chronic diarrhoea due to bile acid malabsorption. Aliment Pharmacol Ther 2014; 39: 923–39. 2. Camilleri M, Acosta A, Busciglio I, et al. Effect of colesevelam on faecal bile acids and bowel functions in diarrhoea-predominant irritable bowel syndrome. Aliment Pharmacol Ther 2015; 41: 438–48. 3. Wedlake L, A’Hern R, Thomas K, Walters JRF, Andreyev HJN. Systematic review: the prevalence of idiopathic bile acid malabsorption (I-BAM) as diagnosed by SeHCAT scanning in patients with diarrhoea-predominant irritable bowel syndrome (IBS). Aliment Pharmacol Ther 2009; 30: 707–17. 4. Camilleri M, Busciglio I, Acosta A, et al. Effect of increased bile acid synthesis or fecal excretion in irritable bowel syndromediarrhea. Am J Gastroenterol 2014; 109: 1621–30. 5. Beigel F, Teich N, Howaldt S, et al. Colesevelam for the treatment of bile acid malabsorption-associated diarrhea in patients with Crohn’s disease: a randomized, double-blind, placebo-controlled study. J Crohns Colitis 2014; 8: 1471–9. 6. Walters JR. Bile acid diarrhoea and FGF19: new views on diagnosis, pathogenesis and therapy. Nat Rev Gastroenterol Hepatol 2014; 11: 426–34.
The observed increase in serum C4 level, a surrogate for the rate of hepatic synthesis of bile acids, may compensate for the intraluminal sequestration by colesevelam of bile acids in the small intestine, and avoid aggravating the mild steatorrhoea observed in these patients with IBS-diarrhoea.3
ACKNOWLEDGEMENT The author’s declarations of personal and financial interests are unchanged from those in the original article.2 REFERENCES 1. Walters JRF, Appleby RN. Editorial: colesevelam effects on faecal bile acids in IBS with diarrhea. Aliment Pharmacol Ther 2015; 41: 696–7. 2. Camilleri M, Acosta A, Busciglio I, et al. Effect of colesevelam on faecal bile acids and bowel functions in diarrhoea-predominant irritable bowel syndrome. Aliment Pharmacol Ther 2015; 41: 438–48. 3. Camilleri M, Busciglio I, Acosta A, et al. Effect of increased bile acid synthesis or fecal excretion in irritable bowel syndromediarrhea. Am J Gastroenterol 2014; 109: 1621–30.
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