Plecanatide favourable for older individuals with CIC, IBS-C
The guanylate cyclase-C receptor agonist plecanatide is effective and well-tolerated by older individuals (≥65 years) with chronic idiopathic constipation (CIC) and irritable bowel syndrome with constipation (IBS-C), results of a post hoc analysis presented at DDW 2020 has shown.
CIC and IBS-C are common chronic gastrointestinal disorders that represent a spectrum of diseases known as functional bowel disorders. [Gastroenterology 2016;150:1393-1407] Although evidence has shown the efficacy of prosecretory agents for short-term treatment of both conditions, data on their efficacy and safety among the elderly are limited. [Pharmacotherapy 2015;35:613-630]
The team pooled data from four 12-week, phase III trials (two CIC and two IBS-C; n=4,973) that randomized participants 1:1:1 to receive plecanatide 3 or 6 mg, or placebo. Of these, 468 were elderly (mean age 70 years, 30 percent male). [DDW 2020, abstract Sa1712]
At week 12, stool consistency in the elderly cohort was significantly improved with both plecanatide doses vs placebo (least-squares [LS] mean, 1.49 vs 0.92; p=0.002 [3 mg] and LS mean, 1.48 vs 0.92; p=0.004 [6 mg]).
Weekly stool frequency was significantly greater with plecanatide 3 mg vs placebo, be it for complete spontaneous bowel movements (CSBM; LS mean, 2.63 vs 1.56; p=0.003) or spontaneous bowel movements (SBM; LS mean, 3.27 vs 1.90; p=0.003).
Moreover, the times from start of treatment to first CSBM were significantly shorter with both plecanatide doses vs placebo (p<0.05 for both).Time to first SBM was substantially shorter with the 6-mg plecanatide dose vs placebo (p<0.05); borderline significance was observed between plecanatide 3 mg and placebo (p=0.05).
Diarrhoea was the most commonly reported treatment-emergent adverse event (TEAE; ranging from 4–5 percent). However, the rates of discontinuation due to diarrhoea were low (1.7–2 percent), and no serious cases were observed. Other common TEAEs reported were headache, flatulence, arthralgia, upper respiratory infection, and nasopharyngitis.
“This is the largest pooled analysis of patients with CIC and IBS-C in the elderly population to date. [Our] results indicate that plecanatide is well-tolerated and effective … for older adult patients with CIC or IBS-C,” said the researchers. The findings correlated with the overall study findings as well as the results pertaining to the younger cohort, they added.
CIC and IBS-C may impair quality of life and work productivity, and carry a substantial cost burden. [J Manag Care Spec Pharm 2014;20:382-390; Am J Gastroenterol 2015;110:580-587] Despite the various therapeutic options* available, no single algorithm suits all patients given the heterogeneity of both conditions. [N Engl J Med 2017;376:2566-2578] Alternatives can provide options in case of initial treatment failure or intolerance. [P T 2018;43:207-209]