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Efficacy of Secretagogues in Patients With Irritable Bowel Syndrome With Constipation: Systematic Review and Network Meta-analysis.
Gastroenterology 2018; 155(6):1753-1763G

Abstract

BACKGROUND & AIMS

Several secretagogues have been approved for the treatment of irritable bowel syndrome with constipation (IBS-C). However, their relative efficacy is unclear because there have been no head-to-head randomized controlled trials. We conducted a network meta-analysis to compare their efficacies in patients with IBS-C.

METHODS

We searched MEDLINE, EMBASE, EMBASE Classic, and the Cochrane Central Register of Controlled Trials through June 2018 to identify randomized controlled trials assessing the efficacy of secretagogues in adults with IBS-C. Trials included in the analysis reported a dichotomous assessment of overall response to therapy, and data were pooled using a random-effects model. Efficacy and safety of secretagogues were reported as a pooled relative risk with 95% confidence interval to summarize the effect of each comparison tested, and treatments were ranked according to their P score.

RESULTS

We identified 15 eligible randomized controlled trials of secretagogues that included 8462 patients. Linaclotide, lubiprostone, plecanatide, and tenapanor were superior to placebo for the treatment of IBS-C. Linaclotide (290 μg once daily) was ranked first in efficacy based on the end point recommended by the Food and Drug Administration for trials in IBS-C, the primary end point used in each trial, abdominal pain, and complete spontaneous bowel movements. Tenapanor (50 mg twice daily) was ranked first for decreasing bloating. Total numbers of adverse events were significantly larger with linaclotide (290 and 500 μg once daily) and plecanatide (3 mg once daily) compared with placebo. However, plecanatide 6 mg once daily ranked first for safety. Diarrhea was significantly more common with all drugs, except lubiprostone (8 μg twice daily). Nausea was significantly more common in patients who received lubiprostone.

CONCLUSIONS

In a network analysis of randomized controlled trials of secretagogues for IBS-C, we found all drugs to be superior to placebo. Efficacy was similar among individual drugs and dosages for most end points. However, data were extracted at the 12-week time point, so the long-term relative efficacy of these drugs is unknown.

Authors+Show Affiliations

Leeds Gastroenterology Institute, St James's University Hospital, Leeds, United Kingdom; Leeds Institute of Biomedical and Clinical Sciences, University of Leeds, Leeds, United Kingdom.Leeds Gastroenterology Institute, St James's University Hospital, Leeds, United Kingdom; Leeds Institute of Biomedical and Clinical Sciences, University of Leeds, Leeds, United Kingdom.Division of Gastroenterology and Hepatology, Lynda K. and David M. Underwood Center for Digestive Disorders, Houston Methodist Hospital and Weill Cornell Medical College, Houston, Texas.Gastroenterology Division, McMaster University, Health Sciences Center, Hamilton, Ontario, Canada.Leeds Institute of Biomedical and Clinical Sciences, University of Leeds, Leeds, United Kingdom.Leeds Gastroenterology Institute, St James's University Hospital, Leeds, United Kingdom; Leeds Institute of Biomedical and Clinical Sciences, University of Leeds, Leeds, United Kingdom. Electronic address: alexf12399@yahoo.com.

Pub Type(s)

Journal Article
Meta-Analysis
Systematic Review

Language

eng

PubMed ID

30144426

Citation

Black, Christopher J., et al. "Efficacy of Secretagogues in Patients With Irritable Bowel Syndrome With Constipation: Systematic Review and Network Meta-analysis." Gastroenterology, vol. 155, no. 6, 2018, pp. 1753-1763.
Black CJ, Burr NE, Quigley EMM, et al. Efficacy of Secretagogues in Patients With Irritable Bowel Syndrome With Constipation: Systematic Review and Network Meta-analysis. Gastroenterology. 2018;155(6):1753-1763.
Black, C. J., Burr, N. E., Quigley, E. M. M., Moayyedi, P., Houghton, L. A., & Ford, A. C. (2018). Efficacy of Secretagogues in Patients With Irritable Bowel Syndrome With Constipation: Systematic Review and Network Meta-analysis. Gastroenterology, 155(6), pp. 1753-1763. doi:10.1053/j.gastro.2018.08.021.
Black CJ, et al. Efficacy of Secretagogues in Patients With Irritable Bowel Syndrome With Constipation: Systematic Review and Network Meta-analysis. Gastroenterology. 2018;155(6):1753-1763. PubMed PMID: 30144426.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Efficacy of Secretagogues in Patients With Irritable Bowel Syndrome With Constipation: Systematic Review and Network Meta-analysis. AU - Black,Christopher J, AU - Burr,Nicholas E, AU - Quigley,Eamonn M M, AU - Moayyedi,Paul, AU - Houghton,Lesley A, AU - Ford,Alexander C, Y1 - 2018/08/23/ PY - 2018/06/28/received PY - 2018/08/14/revised PY - 2018/08/16/accepted PY - 2018/8/26/pubmed PY - 2019/1/8/medline PY - 2018/8/26/entrez KW - Complete Spontaneous Bowel Movement KW - Effectiveness KW - Randomized Controlled Trial Comparison KW - Treatment Response SP - 1753 EP - 1763 JF - Gastroenterology JO - Gastroenterology VL - 155 IS - 6 N2 - BACKGROUND & AIMS: Several secretagogues have been approved for the treatment of irritable bowel syndrome with constipation (IBS-C). However, their relative efficacy is unclear because there have been no head-to-head randomized controlled trials. We conducted a network meta-analysis to compare their efficacies in patients with IBS-C. METHODS: We searched MEDLINE, EMBASE, EMBASE Classic, and the Cochrane Central Register of Controlled Trials through June 2018 to identify randomized controlled trials assessing the efficacy of secretagogues in adults with IBS-C. Trials included in the analysis reported a dichotomous assessment of overall response to therapy, and data were pooled using a random-effects model. Efficacy and safety of secretagogues were reported as a pooled relative risk with 95% confidence interval to summarize the effect of each comparison tested, and treatments were ranked according to their P score. RESULTS: We identified 15 eligible randomized controlled trials of secretagogues that included 8462 patients. Linaclotide, lubiprostone, plecanatide, and tenapanor were superior to placebo for the treatment of IBS-C. Linaclotide (290 μg once daily) was ranked first in efficacy based on the end point recommended by the Food and Drug Administration for trials in IBS-C, the primary end point used in each trial, abdominal pain, and complete spontaneous bowel movements. Tenapanor (50 mg twice daily) was ranked first for decreasing bloating. Total numbers of adverse events were significantly larger with linaclotide (290 and 500 μg once daily) and plecanatide (3 mg once daily) compared with placebo. However, plecanatide 6 mg once daily ranked first for safety. Diarrhea was significantly more common with all drugs, except lubiprostone (8 μg twice daily). Nausea was significantly more common in patients who received lubiprostone. CONCLUSIONS: In a network analysis of randomized controlled trials of secretagogues for IBS-C, we found all drugs to be superior to placebo. Efficacy was similar among individual drugs and dosages for most end points. However, data were extracted at the 12-week time point, so the long-term relative efficacy of these drugs is unknown. SN - 1528-0012 UR - https://www.unboundmedicine.com/medline/citation/30144426/Efficacy_of_Secretagogues_in_Patients_With_Irritable_Bowel_Syndrome_With_Constipation:_Systematic_Review_and_Network_Meta_analysis_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0016-5085(18)34886-8 DB - PRIME DP - Unbound Medicine ER -