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Linaclotide: a guide to its use in irritable bowel syndrome with constipation in the EU

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Abstract

Linaclotide (Constella®) is a novel first-in-class agent for the treatment of adults with moderate to severe irritable bowel syndrome with constipation. It is a synthetic peptide and a potent guanylate cyclase C receptor agonist that acts locally in the gastrointestinal tract to stimulate fluid secretion, increase colonic transit and reduce abdominal pain. Relative to placebo, oral linaclotide 290 µg/once daily significantly improved abdominal symptoms (including bloating and pain/discomfort), bowel function and health-related quality of life in two phase 3 trials. Linaclotide was generally well tolerated for up to 26 weeks.

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References

  1. Longstreth GF, Thompson WG, Chey WD, et al. Functional bowel disorders. Gastroenterology. 2006;130(5):1480–91.

    Article  PubMed  Google Scholar 

  2. Hungin AP, Whorwell PJ, Tack J, et al. The prevalence, patterns and impact of irritable bowel syndrome: an international survey of 40,000 subjects. Aliment Pharmacol Ther. 2003;17(5):643–50.

    Article  PubMed  CAS  Google Scholar 

  3. Constella (linaclotide): summary of product characteristics. London: European Medicines Agency; 2014.

  4. Linzess® (linaclotide) capsules, for oral use: US prescribing information. St. Louis (MI): Forest Laboratories, Inc. and Ironwood Pharmaceuticals, Inc.; 2014.

  5. Busby RW, Kessler MM, Bartolini WP, et al. Pharmacologic properties, metabolism, and disposition of linaclotide, a novel therapeutic peptide approved for the treatment of irritable bowel syndrome with constipation and chronic idiopathic constipation. J Pharmacol Exp Ther. 2013;344(1):196–206.

    Article  PubMed  CAS  Google Scholar 

  6. Bryant AP, Busby RW, Bartolini WP, et al. Linaclotide is a potent and selective guanylate cyclase C agonist that elicits pharmacological effects locally in the gastrointestinal tract. Life Sci. 2010;86(19–20):760–5.

    Article  PubMed  CAS  Google Scholar 

  7. Busby RW, Bryant AP, Bartolini WP, et al. Linaclotide, through activation of guanylate cyclase C, acts locally in the gastrointestinal tract to elicit enhanced intestinal secretion and transit. Eur J Pharmacol. 2010;649(1–3):328–35.

    Article  PubMed  CAS  Google Scholar 

  8. Andresen V, Camilleri M, Busciglio IA, et al. Effect of 5 days linaclotide on transit and bowel function in females with constipation-predominant irritable bowel syndrome. Gastroenterology. 2007;133(3):761–8.

    Article  PubMed  CAS  Google Scholar 

  9. McCormack PL. Linaclotide: a review of its use in the treatment of irritable bowel syndrome with constipation. Drugs. 2014;74(1):53–60.

    Article  PubMed  CAS  Google Scholar 

  10. Castro J, Harrington AM, Hughes PA, et al. Linaclotide inhibits colonic nociceptors and relieves abdominal pain via guanylate cyclase-C and extracellular cyclic GMP. Gastroenterology. 2013;145(6):1334–6.

    Article  PubMed  CAS  Google Scholar 

  11. Rao S, Lembo AJ, Shiff SJ, et al. A 12-week, randomized, controlled trial with a 4-week randomized withdrawal period to evaluate the efficacy and safety of linaclotide in irritable bowel syndrome with constipation. Am J Gastroenterol. 2012;107(11):1714–24.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  12. Chey WD, Lembo AJ, Lavins BJ, et al. Linaclotide for irritable bowel syndrome with constipation: a 26-week, randomized, double-blind, placebo-controlled trial to evaluate efficacy and safety. Am J Gastroenterol. 2012;107(11):1702–12.

    Article  PubMed  CAS  Google Scholar 

  13. Quigley EMM, Tack J, Chey WD, et al. Randomised clinical trials: linaclotide phase 3 studies in IBS-C: a prespecified further analysis based on European Medicines Agency-specified endpoints. Aliment Pharmacol Ther. 2013;37(1):49–61.

    Article  PubMed  CAS  Google Scholar 

  14. Chey W, Lavins B, Shiff S, et al. Is response to linaclotide after 4 weeks of treatment predictive of 12-week improvement? [abstract no. PWE-166]. Gut. 2014;63(Suppl 1):A197–8.

  15. Rao SS, Quigley EM, Shiff SJ, et al. Effect of linaclotide on severe abdominal symptoms in patients with irritable bowel syndrome with constipation. Clin Gastroenterol Hepatol. 2014;12(4):616–23.

    Article  PubMed  CAS  Google Scholar 

  16. Buono JL, Tourkodimitris S, Sarocco P, et al. Impact of linaclotide treatment on work productivity and activity impairment in adults with irritable bowel syndrome with constipation [abstract]. Value Health. 2012;15(7):A330–1.

    Article  Google Scholar 

  17. Lembo A, Carson R, Shiff SJ, et al. Factors contributing to treatment satisfaction in patients with irritable bowel syndrome with constipation (IBS-C) treated with linaclotide vs placebo [abstract no. Tu1401]. Gastroentrology. 2012;142(5 Suppl 1):s822–3.

  18. Irritable bowel syndrome in adults: diagnosis and management of irritable bowel syndrome in primary care (NICE clinical guideline 61). London: National Institute for Health and Clinical Excellence; 2008.

  19. Amitiza® (lubiprostone) capsules: US prescribing information. Bethesda (MD): Sucampo Pharma Americas, LCC; 2013.

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Acknowledgments

The manuscript was reviewed by: E. Obarcanin, Sarajevo, Bosnia and Herzegovina; E.M.M. Quigley, Department of Gastroenterology and Hepatology, The Methodist Hospital and Weill Cornell Medical College, Houston, Texas, USA.

Disclosure

This article was updated from Drugs 2014;74(1):53–60 [9], by contracted/salaried employees of Adis/Springer. The preparation of these reviews was not supported by any external funding. During the peer review process, the manufacturer of the agent under review was offered an opportunity to comment on the article. Changes resulting from comments received were made by the authors on the basis of scientific and editorial merit.

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Authors and Affiliations

  1. Springer, Private Bag 65901, Mairangi Bay, North Shore, 0754, Auckland, New Zealand

    Lily P. H. Yang, Paul L. McCormack & Katherine A. Lyseng-Williamson

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  1. Lily P. H. Yang
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  2. Paul L. McCormack
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  3. Katherine A. Lyseng-Williamson
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Correspondence to Katherine A. Lyseng-Williamson.

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Yang, L.P.H., McCormack, P.L. & Lyseng-Williamson, K.A. Linaclotide: a guide to its use in irritable bowel syndrome with constipation in the EU. Drugs Ther Perspect 30, 342–347 (2014). https://doi.org/10.1007/s40267-014-0155-z

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  • DOI: https://doi.org/10.1007/s40267-014-0155-z

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