Linaclotide Improves Abdominal Pain and Bowel Habits in a Phase IIb Study of Patients With Irritable Bowel Syndrome With Constipation
Open accessAbstract
Background & aims Linaclotide, a minimally absorbed, 14-amino acid peptide agonist of guanylate cyclase-C, has shown benefit in a proof-of-concept study for the treatment of patients with irritable bowel syndrome (IBS) with constipation (IBS-C). We assessed the efficacy and safety of linaclotide at a daily dose range of 75-600 μg in IBS-C.Methods We performed a randomized, double-blind, multicenter, placebo-controlled study of 420 patients with IBS-C given oral linaclotide at doses of 75, 150, 300, or 600 μg or placebo once daily for 12 weeks. End points included change from baseline in daily bowel habits, daily abdominal symptoms, and weekly global assessments, in addition to responder criteria.Results All doses of linaclotide significantly improved bowel habits, including frequency of spontaneous bowel movements and complete spontaneous bowel movements (primary end point), severity of straining, and stool consistency. Abdominal pain was significantly reduced from baseline, compared with placebo; mean changes in abdominal pain (assessed on a 5-point scale) from baseline were -0.71, -0.71, -0.90, and -0.86 for linaclotide doses of 75, 150, 300, and 600 μg, respectively, compared with -0.49 for placebo. Likewise, most doses of linaclotide significantly improved other abdominal symptoms, including discomfort and bloating, and global measures of IBS-C compared with placebo. Effects were observed within the first week and were sustained throughout 12 weeks of treatment. Except for diarrhea, the incidence of adverse events was similar between placebo and linaclotide groups.Conclusions Linaclotide, across a wide range of doses, significantly improved symptoms of IBS-C, including abdominal pain and bowel symptoms. Diarrhea was the only dose-dependent adverse event and was usually of mild or moderate severity.
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The number-needed-to-treat was 11 which should be compared with 4 for 'placebo without deception, 7 for alosetron, 8 for linaclotide and 14 for tegaserod.
“The number-needed-to-treat was 11 which should be compared with 4 for ‘placebo without deception,259 7 for alosetron,260 8 for linaclotide261 and 14 for tegaserod.262”
From Intestinal microbiota in functional bowel disorders: a Rome foundation report (2013) · cites this paper as [261]
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Practical Nonparametric Statistics
Groggel, D. J., & Conover, W. J. (2000) · Technometrics · doi:10.2307/1271101 · Cited by 11,071 · see citing works
Longstreth, G. F., Thompson, W. G., Chey, W. D., Houghton, L. A., Mearin, F., & Spiller, R. C. (2006) · Gastroenterology · doi:10.1053/j.gastro.2005.11.061 · Cited by 4,856 · see citing works
Functional bowel disorders and functional abdominal pain
Thompson, W. G., Longstreth, G. F., Drossman, D. A., Heaton, K. W., Irvine, E. J., & Müller-Lissner, S. A. (1999) · Gut · doi:10.1136/gut.45.2008.ii43 · Cited by 2,440 · see citing works
WINAWER, S. (2003) · Gastroenterology · doi:10.1053/gast.2003.50044 · Cited by 2,143 · see citing works
FRANCIS, C. Y., MORRIS, J., & WHORWELL, P. J. (1997) · Alimentary Pharmacology & Therapeutics · doi:10.1046/j.1365-2036.1997.142318000.x · Cited by 1,708 · see citing works
Patrick, D. L., Drossman, D. A., Frederick, I. O., Dicesare, J., & Puder, K. L. (1998) · Digestive Diseases and Sciences · doi:10.1023/a:1018831127942 · Cited by 761 · see citing works
An Evidence-Based Position Statement on the Management of Irritable Bowel Syndrome
American College of Gastroenterology IBS Task Force (2009) · The American Journal of Gastroenterology · doi:10.1038/ajg.2008.122 · Cited by 694 · see citing works
A placebo-controlled trial of prucalopride for severe chronic constipation
Camilleri, M., Kerstens, R., Rykx, A., & Vandeplassche, L. (2008) · New England Journal of Medicine · doi:10.1056/nejmoa0800670 · Cited by 576 · see citing works
Guanylin: an endogenous activator of intestinal guanylate cyclase.
Currie, M. G., Fok, K. F., Kato, J., Moore, R. J., Hamra, F. K., Duffin, K. L., & Smith, C. E. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.3.947 · Cited by 570 · see citing works
Self-citationIrritable bowel syndrome in the United States: prevalence, symptom patterns and impact
Hungin, A. P. S., Chang, L., Locke, G. R., Dennis, E. H., & Barghout, V. (2005) · Alimentary Pharmacology & Therapeutics · doi:10.1111/j.1365-2036.2005.02463.x · Cited by 494 · see citing works
Andresen, V., Camilleri, M., Busciglio, I. A., Grudell, A., Burton, D. D., McKinzie, S., Foxx–Orenstein, A. E., Kurtz, C. B., Sharma, V., Johnston, J. M., et al. (2007) · Gastroenterology · doi:10.1053/j.gastro.2007.06.067 · Cited by 245 · see citing works
Self-citationBusby, R. W., Bryant, A. P., Bartolini, W. P., Cordero, E. A., Hannig, G., Kessler, M. M., Mahajan‐Miklos, S., Pierce, C. M., Solinga, R. M., Sun, L. J., et al. (2010) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2010.09.019 · Cited by 236 · see citing works
Self-citationInternational Survey of Patients With IBS
Drossman, D. A., Morris, C. B., Wanta, S. E., Hu, Y., Norton, N. J., Norton, W. F., Weinland, S. R., Dalton, C. B., Leserman, J., & Bangdiwala, S. I. (2009) · Journal of Clinical Gastroenterology · doi:10.1097/mcg.0b013e318189a7f9 · Cited by 235 · see citing works
An Evidence-Based Systematic Review on the Management of Irritable Bowel Syndrome
Brandt, L. J., Chey, W. D., Foxx-Orenstein, A. E., Quigley, E. M. M., Schiller, L. R., Schoenfeld, P. S., Spiegel, B. M., Talley, N. J., & Moayyedi, P. (2009) · American Journal of Gastroenterology · doi:10.14309/00000434-200901001-00002 · Cited by 225 · see citing works
Bryant, A. P., Busby, R. W., Bartolini, W. P., Cordero, E. A., Hannig, G., Kessler, M. M., Pierce, C. M., Solinga, R. M., Tobin, J. V., Mahajan‐Miklos, S., et al. (2010) · Life Sciences · doi:10.1016/j.lfs.2010.03.015 · Cited by 209 · see citing works
Self-citationParé, P., Gray, J. R., Lam, S., Balshaw, R. F., Khorasheh, S., Barbeau, M., Kelly, S., & McBurney, C. R. (2006) · Clinical Therapeutics · doi:10.1016/j.clinthera.2006.10.010 · Cited by 199 · see citing works
Eutamène, H., Bradesi, S., Larauche, M. H., Theodorou, V., Beaufrand, C., Ohning, G., Fioramonti, J., Cohen, M. B., Bryant, A., Kurtz, C. B., et al. (2009) · Neurogastroenterology & Motility · doi:10.1111/j.1365-2982.2009.01385.x · Cited by 186 · see citing works
Self-citationAn Office Guide to Whole-Gut Transit Time
Heaton, K. W., & Donnell, L. J. D. O. (1994) · Journal of Clinical Gastroenterology · doi:10.1097/00004836-199407000-00008 · Cited by 168 · see citing works
Uroguanylin and guanylin peptides: pharmacology and experimental therapeutics
FORTEJR, L. (2004) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2004.08.007 · Cited by 155 · see citing works
Predictors of Patient-Assessed Illness Severity in Irritable Bowel Syndrome
Spiegel, B. M. R., Strickland, A., Naliboff, B. D., Mayer, E. A., & Chang, L. (2008) · The American Journal of Gastroenterology · doi:10.1111/j.1572-0241.2008.01997.x · Cited by 123 · see citing works
Pilot Study on the Effect of Linaclotide in Patients With Chronic Constipation
Johnston, J. M., Kurtz, C. B., Drossman, D. A., Lembo, A. J., Jeglinski, B. I., MacDougall, J. E., Antonelli, S. M., & Currie, M. G. (2008) · The American Journal of Gastroenterology · doi:10.1038/ajg.2008.59 · Cited by 119 · see citing works
Self-citationDrossman, D. A., Morris, C. B., Hu, Y., Toner, B. B., Diamant, N. E., Whitehead, W. E., Dalton, C. B., Leserman, J., Patrick, D. L., & Bangdiwala, S. I. (2007) · The American Journal of Gastroenterology · doi:10.1111/j.1572-0241.2007.01283.x · Cited by 117 · see citing works
Whitehead, W. E., Palsson, O. S., Levy, R. L., Feld, A. D., VonKorff, M., & Turner, M. (2006) · The American Journal of Gastroenterology · doi:10.1111/j.1572-0241.2006.00535.x · Cited by 64 · see citing works
Adequate Relief in a Treatment Trial With IBS Patients: A Prospective Assessment
Passos, M. C., Lembo, A. J., Conboy, L. A., Kaptchuk, T. J., Kelly, J. M., Quilty, M. T., Kerr, C. E., Jacobson, E., Hu, R., Friedlander, E., et al. (2009) · The American Journal of Gastroenterology · doi:10.1038/ajg.2009.13 · Cited by 61 · see citing works
Self-citationBuéno, L., Beaufrand, C., Mahajan‐Miklos, S., et al. (2004) · The American Journal of Gastroenterology · doi:10.14309/00000434-200410001-00863 · Cited by 12 · see citing works
Flagged first, then by citations
Research works printed but not linked: 1
- Eutamene H, Gilet M, Beaufrand C, et al. Effect of oral cyclic GMP on two distinct visceral pain models. Neurogastroenterol Motil 2008;22:75.
Cited by
Sorted by citations
Intestinal microbiota in functional bowel disorders: a Rome foundation report
Simrén, M., Barbara, G., Flint, H. J., Spiegel, B. M. R., Spiller, R. C., Vanner, S., Verdu, E. F., Whorwell, P. J., & Zoetendal, E. G. (2013) · Gut · doi:10.1136/gutjnl-2012-302167 · Cited by 939 · see citing works
ACG Clinical Guideline: Management of Irritable Bowel Syndrome
Lacy, B. E., Pimentel, M., Brenner, D. M., Chey, W. D., Keefer, L. A., Long, M. D., & Moshiree, B. (2021) · American Journal of Gastroenterology · doi:10.14309/ajg.0000000000001036 · Cited by 893 · see citing works
Drossman, D. A., Tack, J., Ford, A. C., Szigethy, E., Törnblom, H., & Van Oudenhove, L. (2018) · Gastroenterology · doi:10.1053/j.gastro.2017.11.279 · Cited by 470 · see citing works
American College of Gastroenterology Monograph on Management of Irritable Bowel Syndrome
Ford, A. C., Moayyedi, P., Chey, W. D., Harris, L. A., Lacy, B. E., Saito, Y. A., & Quigley, E. M. M. (2018) · American Journal of Gastroenterology · doi:10.1038/s41395-018-0084-x · Cited by 388 · see citing works
Castro, J., Harrington, A. M., Hughes, P. A., Martin, C. M., Ge, P., Shea, C. M., Jin, H., Jacobson, S., Hannig, G., Mann, E., et al. (2013) · Gastroenterology · doi:10.1053/j.gastro.2013.08.017 · Cited by 295 · see citing works
Self-citationBlack, C. J., Burr, N. E., Quigley, E. M. M., Moayyedi, P., Houghton, L. A., & Ford, A. C. (2018) · Gastroenterology · doi:10.1053/j.gastro.2018.08.021 · Cited by 166 · see citing works
Chang, L., Sultan, S., Lembo, A., Verne, G. N., Smalley, W., & Heidelbaugh, J. J. (2022) · Gastroenterology · doi:10.1053/j.gastro.2022.04.016 · Cited by 163 · see citing works
Self-citationShah, E. D., Kim, H. M., & Schoenfeld, P. (2018) · American Journal of Gastroenterology · doi:10.1038/ajg.2017.495 · Cited by 119 · see citing works
Spiller, R., Pélerin, F., Cayzeele Decherf, A., Maudet, C., Housez, B., Cazaubiel, M., & Jüsten, P. (2016) · United European Gastroenterology Journal · doi:10.1177/2050640615602571 · Cited by 87 · see citing works
Irritable bowel syndrome: a concise review of current treatment concepts
Wall, G. C., Bryant, G. A., Bottenberg, M. M., Maki, E. D., & Miesner, A. R. (2014) · World Journal of Gastroenterology · doi:10.3748/wjg.v20.i27.8796 · Cited by 56 · see citing works
Pharmacokinetic and pharmacodynamic considerations for the current chronic constipation treatments
Müller-Lissner, S. (2013) · Expert Opinion on Drug Metabolism & Toxicology · doi:10.1517/17425255.2013.773972 · Cited by 31 · see citing works
- Authors
- Johnston, J. M., Kurtz, C. B., MacDougall, J. E., Lavins, B. J., Currie, M. G., Fitch, D. A., O'Dea, C., Baird, M., & Lembo, A. J.
- Affiliations
- Ironwood Pharmaceuticals (United States) (US)
- Beth Israel Deaconess Medical Center (US)
- Corresponding author
- Johnston, Jeffrey M.
- Venue
- Gastroenterology
- Publisher
- Elsevier BV
- Published
- 2010-12
- Volume
- 139
- Issue
- 6
- Pages
- 1877-1886.e2
- ISSN
- 0016-5085 (ISSN-L)
- OpenAlex
- W2132145612
- Cited by
- 229
- References
- 25
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 8 · 2023: 5 · 2022: 10 · 2021: 15 · 2020: 4 · 2019: 7 · 2018: 20 · 2017: 14 · 2016: 13 · 2015: 13 · 2014: 22 · 2013: 37 · 2012: 30
- FWCI
- 29.33
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Gastroenterology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ironwood Pharmaceuticals, Incorporated
- Topics
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Inflammatory Bowel Disease
- Health Sciences › Medicine › Epidemiology › Microscopic Colitis
- Keywords
- linaclotide, irritable bowel syndrome with constipation, guanylate cyclase-C agonist, abdominal pain, bowel habits, spontaneous bowel movements, straining, stool consistency, bloating, diarrhea, dose-response relationship, treatment efficacy and safety
- MeSH terms
- Administration, Oral, Adolescent, Adult, Aged, Constipation, Defecation, Diarrhea, Female, Guanylate Cyclase, Humans, Male, Middle Aged, Peptides, Abdominal Pain, Irritable Bowel Syndrome, Young Adult
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