Colon to Rectum
Am J Gastroenterol. 2023;118(5):872−9
Linaclotide reduced response time for irritable bowel syndrome with constipation symptoms: Analysis of 4 ran-domized controlled trials
Introduction: These post-hoc analyses provide clinically relevant data concerning time to response for individual irritable bowel syndrome with constipation (IBS-C) symptoms after linaclotide use.
Methods: Time-to-response data were pooled from 4 randomized controlled trials. Response time for abdominal symptoms (pain, discomfort, and bloating) and complete spontaneous bowel movements (CSBMs) were analyzed using the Kaplan-Meier method; patients were categorized as early responders (≤ 4 weeks), late responders (> 4−12 weeks), or non-responders.
Results: Among 2350 patients (1172 placebo and 1178 linaclotide 290 μg), > 50% of patients with IBS-C who initiated linaclotide treatment expe-rienced a decrease of ≥ 30% in abdominal pain, discomfort, or bloating within 3−4 weeks (median). The median time to achieving ≥ 3 CSBMs was 4 weeks. Although not all linaclotide-treated patients responded within 12 weeks, a late response occurred between 4 and 12 weeks in 1 in 6 patients for abdominal pain and in approximately 1 in 10 patients for CSBM frequency. Comparisons of early responders, late responders, and non-responders for both response definitions indicated that women, Whites, and patients with less severe baseline abdominal symptoms were more likely to respond early.
Discussion: Although treatment responses with linaclotide occurred in > 50% of patients with irritable bowel syndrome with constipation within 4 weeks of treatment initiation, benefits for individual abdominal symptoms and/or complete spontaneous bowel movement frequency can still occur between 4 and 12 weeks. A lack of improvement in 1 symptom does not negate the possibility of response for others, highlighting the importance of discussing all symptoms with patients and not assuming treatment futility at 4 weeks.