Plecanatide effective for IBS with constipation

 

The uroguanylin analogue plecanatide is an effective symptomatic treatment for patients with irritable bowel syndrome with constipation (IBS-C) [1]. An early clinical response to plecanatide appeared to be predictive of overall response after a treatment duration of 12 weeks.

Plecanatide is indicated for the treatment of adults with IBS-C or chronic idiopathic constipation. In two phase 3 trials (NCT02387359 and NCT02493452), the efficacy and safety of plecanatide were demonstrated in patients with IBS-C. The current pooled analysis of these trials evaluated whether the treatment response during week 2 or 4 was predictive of overall treatment response after 12 weeks in 2,176 patients with IBS-C.

At baseline, complete spontaneous bowel movements per week were present in mean 0.25 of patients. The mean number of spontaneous bowel movements per week was 1.46. At baseline, patients had moderately severe abdominal pain (mean severity score of 6.25). The percentage of responders increased from week 2 to week 4:

• from 11.9% to 16.2% in the placebo group;
• from 20.7% to 24.2% of patients who received plecanatide 3 mg; and
• from 20.1% to 24.3% of patients who received plecanatide 6 mg.

Across weeks 1-12, significantly more plecanatide-treated patients were overall responders compared with the placebo group:

• 0% in the placebo group;
• 6% in the plecanatide 3 mg group (P<0.001 vs placebo); and
• 7% in the plecanatide 6 mg group (P< 0.001 vs placebo).

Being a weekly responder during either week 2 or 4 was significantly predictive of overall-responder status during weeks 1-12.

Patients experiencing a response at week 2 were 29.5 times more likely to be overall responders than those who did not experience a response at week 2 (P<0.001). Furthermore, patients with a response in week 4 were 61.3 times more likely to be overall responders than those who did not experience a response in week 4 (P<0.001). Similar results were found in patients with a sustained response (overall responders who were weekly responders for ≥2 of the last 4 weeks).

Plecanatide, both dosed at 3 mg and 6 mg, was found to be an effective symptomatic treatment for IBS-C. A clinical response to plecanatide as early as week 2 appeared to be predictive of overall response after 12 weeks of treatment.

1. Quigley EM. Early response to plecanatide predicts overall and sustained efficacy in patients with irritable bowel syndrome with constipation. UEG Week Virtual 2020, abstract OP057.

Posted on 2 November 202017 May 2024