Elderly patients with constipation show favourable response to plecanatide

Use of plecanatide for treating elderly patients with chronic idiopathic constipation (CIC) or irritable bowel syndrome with constipation (IBS-C) is well tolerated and improves stool frequency and form, proving to be just as safe and effective as it is in younger populations, as shown in a recent study.

“In general, treatment regimens for older patients with chronic constipation need to be individualized and factor in patients' medical history, medication profile, tolerance to various medications, and clinical status (eg, cognition and physical ability),” according to the authors. [Clin Interv Aging 2015;10:919-930]

“Prosecretory agents [such as plecanatide] are efficacious… however, data are limited regarding the safety and efficacy of these agents for the treatment of constipation in elderly populations,” they added. [Pharmacotherapy 2015;35:613-630]

To address the gap, the authors pooled data from two phase III CIC and two phase III IBS-C trials evaluating two doses of plecanatide. The total population comprised 451 patients aged ≥65 years (plecanatide: n=287 [3 mg: n=150; 6 mg: n=137]; placebo: n=164) and 4,364 patients aged <65 years (plecanatide: n=2,914 [3 mg: n=1,451; 6 mg: n=1,463]; placebo: n=1,450). Mean ages in the older and younger cohorts were 70.0 and 41.9 years. Other patient characteristics were generally similar between the cohorts.

No new safety issues with plecanatide emerged among elderly patients relative to those who were younger. Diarrhoea was the most frequently reported treatment-emergent adverse event (TEAE), occurring in 5.6 percent of patients in the older cohort vs 4.6 percent in the younger cohort with the study drug, and in 1.9 percent and 1.0 percent of patients, respectively, with placebo. [Clin Ther 2020;doi:10.1016/j.clinthera.2020.05.012]

Rates of TEAE-related treatment discontinuation, including those attributable to diarrhoea, across the placebo and plecanatide treatment groups were slightly higher among patients aged ≥65 years (4.2 percent overall and 1.8 percent diarrhoea related) than among younger patients (2.7 percent overall and 1.2 percent diarrhoea related). This indicates a partial effect of age not related to treatment, the authors noted.

“No dose-related trend with plecanatide 3 mg and 6 mg was observed in the rate of drug use discontinuation attributable to TEAEs overall or to diarrhoea specifically,” they added.

In terms of efficacy, 3-mg and 6-mg plecanatide produced marked improvements in stool consistency from baseline at week 12 compared with placebo in both the older (mean change in Bristol Stool Form Scale [BSFS], 1.49 and 1.48 vs 0.92, respectively) and younger cohorts (mean BSFS change, 1.48 and 1.45 vs 0.94, respectively).

Furthermore, weekly bowel movements, both spontaneous (SBM) and complete spontaneous (CSBM), increased more with the study drug than with placebo, with the difference being significant for only the standard 3-mg dose in the older cohort but for both the 3-mg and 6-mg doses in the younger cohort.

Plecanatide also shortened the time from treatment initiation to first CSBM among older patients (3 and 6 mg vs placebo, p<0.05), as well as the time to first SBM (6 mg vs placebo, p<0.05; 3 mg vs placebo, p=0.054). Results were similar in the younger cohort.

Data on the safety and efficacy of other secretagogues, particularly linaclotide and lubiprostone, in elderly patients with CIC and IBS-C are consistent with the findings on plecanatide. [Gastroenterology 2010;138:886-895; Gastroenterology 2006;130:A188–A189]

“A major strength of the current analysis is that it is the largest evaluation of any constipation medication studied within an elderly population… [T]he current Rome IV criteria lend support to the concept of combining the populations from both CIC and IBS-C trials because [the two medical conditions] are now recognized as existing on a single continuous spectrum of disease,” the authors said. [Gastroenterology 2016;150:1393-1407]