IDDF2024-ABS-0438 Does linaclotide have high predictability of defecation? A post-hoc analysis of apple trial

<h3>Background</h3> Many patients with constipation are not satisfied with the predictability of defecation after taking laxatives and expect laxatives with fast responses that can predict the timing of defecation. Linaclotide, a GC -C receptor agonist, is recently approved for chronic constipation with an early onset of action. However, there is a limited information about the onset of defecation after taking linaclotide. We aimed to investigate the reactivity to defecation of a single-dose of linaclotide in chronic constipated patients. <h3>Methods</h3> We performed a post-hoc analysis in constipated patients with a per-protocol group of APPLE trial; reporting the efficacy of 0.5 mg dose of linaclotide vs 24 mg dose of senna as an adjuvant for bowel preparation (BP). We assessed the first defecation time, defecation frequency, and adverse events after taking either of the adjuvant until the start of BP solution on the day of the colonoscopy. The degree of constipation was measured using the Constipation Scoring System (CSS; range, 0–30). <h3>Results</h3> Among 352 constipated patients, 170 patients receiving linaclotide and 182 patients receiving senna were evaluated. The baseline characteristics of the two groups were comparable, and the median (IQR) CSS score was similar between the two groups; 6 (3–9) in the linaclotide group and 6 (3–9) in the senna group (<i>P</i>=0.50). The rate of having at least one defecation until the morning was significantly higher in the linaclotide group than in the senna group (59% vs. 39%, <i>P</i>&lt;0.01), and the median (IQR) first defecation time (hours) was faster in the linaclotide group than in the senna group (2.8 (1.5-8.8) vs. 9.9 (8.3-11), <i>P</i>&lt;0.01). The median frequency (IQR) of defecation was also higher in the linaclotide group than in the senna group (1 (0-2) vs. 0 (0-1), <i>P</i>&lt;0.01). Adverse events including vomiting, abdominal pain and discomfort, and quality of sleep were comparable between the two groups. <h3>Conclusions</h3> A single dose of linaclotide had an early onset of defecation without reducing the patient’s tolerability compared to senna. It may be a promising treatment drug for constipation with high predictability.