PMID-29376436 – Plecanatide Efficacy Safety IBS-C
Brenner DM, Fogel R, Dorn SD, et al. "Efficacy and safety of plecanatide in treating constipation-predominant irritable bowel syndrome," Am J Gastroenterol, 2018;113(5):735-745.
Quick Reference
| Property | Value |
|---|---|
| PMID | 29376436 |
| DOI | 10.1038/s41395-018-0029-8 |
| Year | 2018 |
| Journal | American Journal of Gastroenterology |
| Study Type | Randomized Controlled Trial (Phase III) |
| Evidence Level | I |
| Sample | n=2,189 patients with IBS-C |
| Peptide(s) Studied | Plecanatide |
Key Findings
- Plecanatide 3 mg significantly improved the FDA composite endpoint responder rate vs placebo (30.2% vs 17.8%, P<0.001)
- Significant improvements in both abdominal pain and bowel movement frequency
- Abdominal pain responder rate significantly greater with plecanatide vs placebo
- CSBM responder rates also significantly improved
- Diarrhea was the most common adverse event but incidence was low (~4%)
- These data led to the expanded FDA approval of plecanatide for IBS-C in 2018
Study Design
Two identical Phase III, multicenter, randomized, double-blind, placebo-controlled trials (Study 1 and Study 2). Patients meeting Rome III criteria for IBS-C were randomized to plecanatide 3 mg or placebo once daily for 12 weeks. Primary endpoint: FDA combined abdominal pain and CSBM composite responder. Secondary endpoints included individual symptom improvements.
Limitations
- 12-week treatment period; long-term durability unknown
- 3 mg dose only (no dose-ranging in IBS-C)
- Industry-sponsored (Synergy Pharmaceuticals)
- Rome III criteria used (subsequently updated to Rome IV)
- No head-to-head comparison with linaclotide
Clinical Relevance
This pair of Phase III trials established plecanatide's efficacy in IBS-C, demonstrating significant improvements in the FDA composite endpoint that captures both pain relief and bowel function. The relatively low diarrhea rate compared to linaclotide trials may reflect plecanatide's pH-dependent activation in the proximal intestine, mimicking the endogenous uroguanylin system more closely. This provides clinicians with an alternative GC-C agonist, particularly for patients experiencing diarrhea with linaclotide.
Related
#research #RCT #evidence-level-I #gastrointestinal #plecanatide