METHODS:

Patients with IBS-C with abdominal pain≥ 3 (0–10 scale) were randomized to linaclotide 290 μg or placebo daily for 12 weeks. The AS, derived from the Diary for IBS Symptoms-Constipation, is the average of abdominal bloating, discomfort, and pain at their worst (0= none, 10= worst possible). The primary end point was overall change from baseline (CFB) in AS. Secondary end points included CFB in 12-week AS evaluated using cumulative distribution function and 6-week/12-week AS responder (AS improvement≥ 2 points for≥ 6-week/12-week).

RESULTS:

Overall, 614 patients (mean age 46.7 years; 81% female) were randomized. All prespecified end points showed significant benefit of linaclotide vs placebo. The mean overall CFB AS reduction for linaclotide was− 1.9 vs− 1.2 for placebo (P< 0.0001); the 6-week/12-week AS responder rate was 40.5% for linaclotide vs 23.4% for placebo (odds ratio= 2.2 [95% confidence interval, 1.55–3.12; P< 0.0001]). Diarrhea was the most common treatment-emergent adverse event (linaclotide= 4.6%, placebo= 1.6%).

DISCUSSION:

Linaclotide significantly reduced multiple abdominal symptoms important to patients with IBS-C (bloating, discomfort, and pain) compared with placebo, as measured by a novel multi-item AS. The AS, derived from the Diary for IBS Symptoms-Constipation, should be considered for use in future IBS-C clinical studies to measure clinically meaningful improvements beyond traditional end points.