[en] OBJECTIVES: Diarrhea is one of the main symptoms of Crohn's disease (CD). It is usually significantly improved with specific CD treatments, loperamide or cholestyramine. However, in some cases, diarrhea becomes refractory. The aim of this study was to assess the safety and efficacy of octreotide in this situation. MATERIALS AND METHODS: Fifteen patients with CD refractory diarrhea defined by at least an average of five smooth or liquid stools per day despite an optimized CD treatment were included from three Belgian centers. Two patients were lost to follow-up. A subcutaneous injection of 100 mug octreotide was performed three times a day during three days. When the drug had been well tolerated, an intramuscular injection of 30 mg octreotide (Sandostatin(R) LAR 30) was realized. Evaluation was done at day 31. The primary endpoint was to assess the effect on the mean number of smooth or liquid stools per day. RESULTS: A significant reduction (p = 0.0001) of the average number of smooth or liquid stools over the last seven days was observed between baseline and day 31. The maximum number of smooth or liquid stools also significantly decreased (p = 0.0009). Four patients (26.7%) presented mild nonspecific adverse events but no serious one. We also observed a significant decrease (p = 0.0006) of the Harvey-Bradshaw Index (HBI) and a significant improvement (p = 0.0012) of the inflammatory bowel disease questionnaire (IBDQ). CONCLUSIONS: In this uncontrolled open-label study, octreotide appeared safe and effective in CD refractory diarrhea, in addition to CD treatments. It significantly improved the number of liquid or smooth stools, the HBI and the IBDQ.
Disciplines :
Gastroenterology & hepatology
Author, co-author :
Martelli, Laura
Colard, Arnaud
Fontaine, Fernand
Deflandre, Jacques
Bastens, Boris
Louis, Edouard ; Université de Liège - ULiège > Département des sciences cliniques > Hépato-gastroentérologie
Language :
English
Title :
Evaluation of the efficacy of octreotide LAR in the treatment of Crohn's disease associated refractory diarrhea.
O’Donnell LJ, Watson AJ, Cameron D, et al. Effect of octreotide on mouth-to-caecum transit time in healthy subjects and in the irritable bowel syndrome. Aliment Pharmacol Ther. 1990;4:177–181.
Edwards C, Cann PA, Read NW, et al. Effect of two new antisecretory drugs on fluid and electrolyte transport in a patient with secretory diarrhoea. Gut. 1986;27:581–586.
Cooper JC, Williams NS, King RF, et al. Effects of a long-acting somatostatin analogue in patients with severe ileostomy diarrhoea. Br J Surg. 1986;73:128–131.
Chowers Y, Cahalon L, Lahav M, et al. Somatostatin through its specific receptor inhibits spontaneous and TNF-alpha and bacteria-induced IL-8 and IL-1 beta secretion from intestinal epithelial cells. J Immunol. 2000;165:2955–2961.
Lewis SJ, Heaton KW., Stool form scale as a useful guide to intestinal transit time. Scand J Gastroenterol. 1997;32:920–924.
Harvey RF, Bradshaw JM., A simple index of Crohn's-disease activity. Lancet. 1980;1:514.
Guyatt G, Mitchell A, Irvine EJ, et al. A new measure of health status for clinical trials in inflammatory bowel disease. Gastroenterology. 1989;96:804–810.
Ghosh S, Mitchell R., Impact of inflammatory bowel disease on quality of life:results of the European Federation of Crohn's and Ulcerative Colitis Associations (EFCCA) patient survey. J Crohns Colitis. 2007;1:10–20.
Lönnfors S, Vermeire S, Greco M, et al. IBD and health-related quality of life–discovering the true impact. J Crohns Colitis. 2014;8:1281–1286.
Best WR, Becktel JM, Singleton JW, et al. Development of a Crohn’s disease activity index. National Cooperative Crohn’s Disease Study. Gastroenterology. 1976;70:439–444.
Irvine EJ, Zhou Q, Thompson AK. The short inflammatory bowel disease questionnaire:a quality of life instrument for community physicians managing inflammatory bowel disease. Am J Gastroenterol. 1996;91:1571–1578.
Thia K, Faubion WA, Jr, Loftus EV, Jr, et al. Short CDAI:development and validation of a shortened and simplified Crohn’s disease activity index. Inflamm Bowel Dis. 2011;17:105–111.
Alrubaiy L, Cheung WY, Dodds P, et al. Development of a short questionnaire to assess the quality of life in Crohn’s disease and ulcerative colitis. J Crohns Colitis. 2015;9:66–76.
Williet N, Sandborn WJ, Peyrin-Biroulet L., Patient-reported outcomes as primary end points in clinical trials of inflammatory bowel disease. Clin Gastroenterol Hepatol. 2014;12:1246–1256.
Khanna R, Zou G, D'Haens G, et al. A retrospective analysis:the development of patient reported outcome measures for the assessment of Crohn's disease activity. Aliment Pharmacol Ther. 2015;41:77–86.
Kappelman MD, Long MD, Martin C, et al. Evaluation of the patient reported outcomes measurement information system in a large cohort of patients with inflammatory bowel diseases. Clin Gastroenterol Hepatol. 2014;12:1315–1323.
Gater A, Kitchen H, Heron L, et al. Development of a conceptual model evaluating the humanistic and economic burden of Crohn's disease:implications for patient-reported outcomes measurement and economic evaluation. Expert Rev Pharmacoecon Outcomes Res. 2015;15:643–656.
Wass JA, Popovic V, Chayvialle JA. Proceedings of the discussion, “Tolerability and safety of Sandostatin”. Metab Clin Exp. 1992;41:80–82.
Bornschein J, Drozdov I, Malfertheiner P., Octreotide LAR:safety and tolerability issues. Expert Opin Drug Saf. 2009;8:755–768.