Abstract
BACKGROUND: Linaclotide is approved for the treatment of moderate-to-severe irritable bowel syndrome (IBS) with constipation (IBS-C) in adults. This study aimed to assess factors predictive of a clinical response and improvements in non-IBS symptoms with linaclotide treatment in a Spanish patient population. METHODS: In this open-label phase IIIb study, patients with moderate-to-severe IBS-C received linaclotide 290 μg once daily for 12 weeks. The primary endpoint was clinical response at week 12, defined as >30% reduction in IBS symptom severity score (IBS-SSS) or IBS-SSS <75 plus self-reported response of feeling 'better' or 'much better' versus the baseline. Digestive nonintestinal and extra-digestive symptom scores were assessed. Baseline characteristics and week 4 clinical response were assessed as predictors of week 12 clinical response. RESULTS: A total of 96 patients were eligible; 91 were female and the mean age was 47.4 years. Mean (SD) baseline IBS-SSS was 371 (72.5). In the intention-to-treat and per-protocol populations, 22.9% and 31.7% were clinical responders at week 4, respectively, and 25.0% and 36.7% were clinical responders at week 12. Digestive nonintestinal and extra-digestive symptom scores were significantly improved at weeks 4 and 12. Baseline characteristic was not associated with week 12 clinical response; however, clinical response at week 4 was predictive of response at week 12 (OR: 6.5; 95%IC: 2.1-19.8). The most common adverse event was diarrhea inclusive of loose or watery stools (35.4%). CONCLUSIONS: Linaclotide improves IBS-C symptoms, including digestive nonintestinal and extra-digestive symptoms. A clinical response at week 4 may predict response at week 12.