Systematic review with meta-analysis

Highly selective 5-HT4 agonists (prucalopride, velusetrag or naronapride) in chronic constipation

Andrea Shin, M. Camilleri, G. Kolar, P. Erwin, C. P. West, M. H. Murad

Research output: Contribution to journalArticle

70 Citations (Scopus)

Abstract

Background Highly selective 5-HT4 agonists have been suggested for the treatment of chronic constipation (CC). Aim To assess the effects of highly selective 5-HT4 agonists (prucalopride, velusetrag or naronapride) on patient-important clinical efficacy outcomes and safety in adults with CC. Methods We searched the medical literature in January 2013 using MEDLINE/Pubmed, Embase, Cochrane Library, and Web of Science/Scopus for randomised, controlled trials of highly selective 5-HT4 agonists in adults with CC, with no minimum duration of therapy (maximum 12 weeks) or date limitations. Data were extracted from intention-to-treat analyses, pooled using a random-effects model, and reported as relative risk (RR), mean differences, or standardised mean differences with 95% confidence intervals (CI). Results Main outcomes included stool frequency, Patient-Assessment of Constipation Quality of Life (PAC-QOL), PAC of symptoms (PAC-SYM) and adverse events. Thirteen eligible trials were identified: 11 prucalopride, 1 velusetrag, 1 naronapride. Relative to control, treatment with highly selective 5-HT4 agonists was superior for all outcomes: mean ≥3 spontaneous complete bowel movements (SCBM)/week (RR = 1.85; 95% CI 1.23-2.79); mean ≥1 SCBM over baseline (RR = 1.57; 95% CI 1.19, 2.06); ≥1 point improvement in PAC-QOL and PAC-SYM scores. The only active comparator trial of prucalopride and PEG3350 suggested PEG3350 is more efficacious for some end points. Adverse events were more common with highly selective 5-HT4 agonists, but were generally minor; headache was the most frequent. Most trials studied prucalopride. Conclusion Demonstration of efficacy on patient-important outcomes and a favourable safety profile support the continued use and development of highly selective 5-HT 4 agonists in the treatment of chronic constipation.

Original languageEnglish (US)
Pages (from-to)239-253
Number of pages15
JournalAlimentary Pharmacology and Therapeutics
Volume39
Issue number3
DOIs
StatePublished - 2014
Externally publishedYes

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prucalopride
Serotonin 5-HT4 Receptor Agonists
Constipation
Meta-Analysis
Confidence Intervals
Library Science
Quality of Life
Safety
Serotonin Receptor Agonists
Intention to Treat Analysis
Therapeutics
PubMed
MEDLINE
Headache
TD-5108
ATI 7505
Randomized Controlled Trials

ASJC Scopus subject areas

  • Pharmacology (medical)

Cite this

Systematic review with meta-analysis : Highly selective 5-HT4 agonists (prucalopride, velusetrag or naronapride) in chronic constipation. / Shin, Andrea; Camilleri, M.; Kolar, G.; Erwin, P.; West, C. P.; Murad, M. H.

In: Alimentary Pharmacology and Therapeutics, Vol. 39, No. 3, 2014, p. 239-253.

Research output: Contribution to journalArticle

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abstract = "Background Highly selective 5-HT4 agonists have been suggested for the treatment of chronic constipation (CC). Aim To assess the effects of highly selective 5-HT4 agonists (prucalopride, velusetrag or naronapride) on patient-important clinical efficacy outcomes and safety in adults with CC. Methods We searched the medical literature in January 2013 using MEDLINE/Pubmed, Embase, Cochrane Library, and Web of Science/Scopus for randomised, controlled trials of highly selective 5-HT4 agonists in adults with CC, with no minimum duration of therapy (maximum 12 weeks) or date limitations. Data were extracted from intention-to-treat analyses, pooled using a random-effects model, and reported as relative risk (RR), mean differences, or standardised mean differences with 95{\%} confidence intervals (CI). Results Main outcomes included stool frequency, Patient-Assessment of Constipation Quality of Life (PAC-QOL), PAC of symptoms (PAC-SYM) and adverse events. Thirteen eligible trials were identified: 11 prucalopride, 1 velusetrag, 1 naronapride. Relative to control, treatment with highly selective 5-HT4 agonists was superior for all outcomes: mean ≥3 spontaneous complete bowel movements (SCBM)/week (RR = 1.85; 95{\%} CI 1.23-2.79); mean ≥1 SCBM over baseline (RR = 1.57; 95{\%} CI 1.19, 2.06); ≥1 point improvement in PAC-QOL and PAC-SYM scores. The only active comparator trial of prucalopride and PEG3350 suggested PEG3350 is more efficacious for some end points. Adverse events were more common with highly selective 5-HT4 agonists, but were generally minor; headache was the most frequent. Most trials studied prucalopride. Conclusion Demonstration of efficacy on patient-important outcomes and a favourable safety profile support the continued use and development of highly selective 5-HT 4 agonists in the treatment of chronic constipation.",
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N2 - Background Highly selective 5-HT4 agonists have been suggested for the treatment of chronic constipation (CC). Aim To assess the effects of highly selective 5-HT4 agonists (prucalopride, velusetrag or naronapride) on patient-important clinical efficacy outcomes and safety in adults with CC. Methods We searched the medical literature in January 2013 using MEDLINE/Pubmed, Embase, Cochrane Library, and Web of Science/Scopus for randomised, controlled trials of highly selective 5-HT4 agonists in adults with CC, with no minimum duration of therapy (maximum 12 weeks) or date limitations. Data were extracted from intention-to-treat analyses, pooled using a random-effects model, and reported as relative risk (RR), mean differences, or standardised mean differences with 95% confidence intervals (CI). Results Main outcomes included stool frequency, Patient-Assessment of Constipation Quality of Life (PAC-QOL), PAC of symptoms (PAC-SYM) and adverse events. Thirteen eligible trials were identified: 11 prucalopride, 1 velusetrag, 1 naronapride. Relative to control, treatment with highly selective 5-HT4 agonists was superior for all outcomes: mean ≥3 spontaneous complete bowel movements (SCBM)/week (RR = 1.85; 95% CI 1.23-2.79); mean ≥1 SCBM over baseline (RR = 1.57; 95% CI 1.19, 2.06); ≥1 point improvement in PAC-QOL and PAC-SYM scores. The only active comparator trial of prucalopride and PEG3350 suggested PEG3350 is more efficacious for some end points. Adverse events were more common with highly selective 5-HT4 agonists, but were generally minor; headache was the most frequent. Most trials studied prucalopride. Conclusion Demonstration of efficacy on patient-important outcomes and a favourable safety profile support the continued use and development of highly selective 5-HT 4 agonists in the treatment of chronic constipation.

AB - Background Highly selective 5-HT4 agonists have been suggested for the treatment of chronic constipation (CC). Aim To assess the effects of highly selective 5-HT4 agonists (prucalopride, velusetrag or naronapride) on patient-important clinical efficacy outcomes and safety in adults with CC. Methods We searched the medical literature in January 2013 using MEDLINE/Pubmed, Embase, Cochrane Library, and Web of Science/Scopus for randomised, controlled trials of highly selective 5-HT4 agonists in adults with CC, with no minimum duration of therapy (maximum 12 weeks) or date limitations. Data were extracted from intention-to-treat analyses, pooled using a random-effects model, and reported as relative risk (RR), mean differences, or standardised mean differences with 95% confidence intervals (CI). Results Main outcomes included stool frequency, Patient-Assessment of Constipation Quality of Life (PAC-QOL), PAC of symptoms (PAC-SYM) and adverse events. Thirteen eligible trials were identified: 11 prucalopride, 1 velusetrag, 1 naronapride. Relative to control, treatment with highly selective 5-HT4 agonists was superior for all outcomes: mean ≥3 spontaneous complete bowel movements (SCBM)/week (RR = 1.85; 95% CI 1.23-2.79); mean ≥1 SCBM over baseline (RR = 1.57; 95% CI 1.19, 2.06); ≥1 point improvement in PAC-QOL and PAC-SYM scores. The only active comparator trial of prucalopride and PEG3350 suggested PEG3350 is more efficacious for some end points. Adverse events were more common with highly selective 5-HT4 agonists, but were generally minor; headache was the most frequent. Most trials studied prucalopride. Conclusion Demonstration of efficacy on patient-important outcomes and a favourable safety profile support the continued use and development of highly selective 5-HT 4 agonists in the treatment of chronic constipation.

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