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

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