Abstract

Linaclotide Reduced Response Time for Irritable Bowel Syndrome with Constipation Symptoms: Analysis of Four Randomized Controlled Trials

Am J Gastroenterol. 2022 Oct 12. doi: 10.14309/ajg.0000000000002064. Online ahead of print.

 

Darren M Brenner 1Brian E Lacy 2Alexander C Ford 3 4Wilmin Bartolini 5James Wu 5Elizabeth P Shea 5Wieslaw Bochenek 6Ramesh Boinpally 6Cristina Almansa 5

 
     

Author information

1Northwestern University Feinberg School of Medicine, Chicago, IL, USA.

2Mayo Clinic, Jacksonville, FL, USA.

3Leeds Institute of Medical Research at St. James's, University of Leeds, Leeds, UK.

4Leeds Gastroenterology Institute, Leeds Teaching Hospitals NHS Trust, Leeds, UK.

5Ironwood Pharmaceuticals, Inc., Boston, MA, USA.

6AbbVie Inc., Madison, NJ, USA.

Abstract

Objectives: These post hoc analyses provide clinically relevant data concerning time to response for individual irritable bowel syndrome with constipation (IBS-C) symptoms following linaclotide use.

Methods: Time to response data were pooled from four 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" (≤4 weeks), "late" (>4-12 weeks), or "non-"responders.

Results: Among 2,350 patients (1,172 placebo and 1,178 linaclotide 290 μg), >50% of patients with IBS-C who initiated linaclotide treatment experienced a decrease of ≥30% in abdominal pain, discomfort, or bloating within 3-4 weeks (median). 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 one in six patients for abdominal pain, and in approximately one in ten patients for CSBM frequency. Comparisons of "early", "late", and "non-"responders for both response definitions indicated that females, Caucasians, and patients with less severe baseline abdominal symptoms were more likely to respond early.

Conclusions: Although treatment responses with linaclotide occurred in >50% of patients with IBS-C within 4 weeks of treatment initiation, benefits for individual abdominal symptoms and/or CSBM frequency can still occur between 4 and 12 weeks. A lack of improvement in one 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.

 

 

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