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Reference - Am J Gastroenterol 2017 Feb 7 early online (level 1 [likely reliable] evidence)
- Prosecretory agents are a treatment option for patients with constipation refractory to dietary modifications, osmotic laxatives, and stimulant laxatives.
- Plecanatide is a new uroguanylin analog that increases intestinal fluid secretion, aiding regular bowel movements.
- In a trial of 1,394 adults with chronic idiopathic constipation randomized to plecanatide vs. placebo for 12 weeks, plecanatide significantly increased the frequency of bowel movements and improved patient assessment of constipation severity.
Chronic constipation can interfere with daily activities, thereby negatively impacting quality of life. In patients with constipation without signs or symptoms indicating need for further diagnostic testing, initial management recommended by The American Society of Colon and Rectal Surgeons includes dietary modification and fluid supplementation followed by the use of osmotic laxatives, and in the short term, stimulant laxatives. For patients refractory to these therapies, the guidelines indicate that prosecretory agents may be considered. A new prosecretory agent, plecanatide, is a guanylate cyclase-C agonist that binds to the luminal surface of the intestinal epithelium resulting in local fluid secretion, promoting hydration and transit of stools (US Food & Drug Administration). The efficacy of plecanatide to increase bowel movement frequency and alleviate symptoms of constipation was investigated in a recent trial involving 1,394 adults (mean age 46 years) with chronic idiopathic constipation. The adults were randomized to plecanatide at either 3 mg or 6 mg once daily, or placebo for 12 weeks. The primary outcome was a durable response defined as ≥ 3 complete spontaneous bowel movements (CSBMs) per week and an increase from baseline of at least one CSBM for that week, for ≥ 9 weeks including at least 3 of the 4 last weeks of treatment. Bisacodyl was provided as a rescue medication, but bowel movements were only counted if they occurred without rescue medication use within the previous 24 hours. Patients were required to refrain from taking protocol-prohibited medications, but it is unclear from the article what these included.
Similar rates of outcomes were observed for the two doses of plecanatide, and only the results pertaining to the 3 mg dose are reported here. Comparing plecanatide 3 mg to placebo, a durable response was reported in 21% vs. 10.2% (p < 0.001, NNT 10) and the mean increase in weekly frequency of CSBMs from baseline was 2.5 vs. 1.2 (p < 0.001). Plecanatide was also associated with significantly improved patient global assessment of constipation severity, stool consistency, and symptoms of straining, bloating, and discomfort. Diarrhea was more common with plecanatide, being reported in 5.9% of patients on the active drug vs. 1.3% with placebo (statistical comparisons not reported). Two weeks after stopping treatment, the frequency of CSBMs decreased in both groups but did not return to baseline levels. Rates of rescue medication use were not reported.
This trial found an early and sustained improvement in bowel movement frequency and stool consistency over 12 weeks of plecanatide treatment compared to placebo. Moreover, patients taking plecanatide reported less severe constipation and greater satisfaction with treatment. Short-term safety assessment indicated similar rates among groups in overall or serious treatment-emergent adverse events. The rate of discontinuing study medication due to an adverse event was 5.1% for patients taking plecanatide vs. 1.3% for placebo. Other prosecretory agents such as lubiprostone and linaclotide are available, and head to head trials will be necessary to evaluate their comparative efficacies. In summary, plecanatide provides another treatment option for patients with chronic idiopathic constipation to be offered after carefully documented lack of sufficient response to dietary modifications, and use of osmotic and stimulant laxatives.
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