Efficacy of Linaclotide in Reducing Abdominal Symptoms of Bloating, Discomfort, and Pain: A Phase 3B Trial Using a Novel Abdominal Scoring System.
Am J Gastroenterol
; 116(9): 1929-1937, 2021 09 01.
Article
em En
| MEDLINE
| ID: mdl-34465695
ABSTRACT
INTRODUCTION:
Linaclotide improves abdominal pain and constipation in patients with constipation-predominant irritable bowel syndrome (IBS-C). Patients report additional bothersome abdominal symptoms of bloating and discomfort. The intention of this study was to evaluate linaclotide's efficacy in relieving IBS-C-related abdominal symptoms (bloating, discomfort, and pain) using a novel multi-item Abdominal Score (AS).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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Peptídeos
/
Fármacos Gastrointestinais
/
Dor Abdominal
/
Constipação Intestinal
/
Agonistas da Guanilil Ciclase C
Tipo de estudo:
Clinical_trials
/
Diagnostic_studies
Limite:
Adult
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article