Linaclotide May Produce Early or Late Treatment Response in IBS-C

Patients with IBS-C may experience treatment response on linaclotide between 4 and 12 weeks.

While more than half of patients with irritable bowel syndrome with constipation (IBS-C) respond early to treatment with linaclotide, other patients experience a late response, according to study findings published in the American Journal of Gastroenterology.

Researchers conducted pooled posthoc analyses of 4 randomized controlled trials that analyzed time to response in 2350 patients receiving treatment (linaclotide 290 mcg, n=1178; placebo, n=1172) for IBS-C symptoms. Patients were categorized into 3 groups based on responsiveness to linaclotide: nonresponders, early responders (≤ 4 weeks), and late responders (>4-12 weeks).

Patient responsiveness to linaclotide was based on the ability to have complete spontaneous bowel movements and reports of decreased abdominal symptoms, such as pain, bloating, or discomfort.

The researchers observed a clear difference between the linaclotide and placebo groups according to time-to-response (P <.0001 for each abdominal symptom). More than 50% of patients taking linaclotide were early responders, experiencing decreased abdominal pain and abdominal discomfort within a median of 3 weeks and decreased abdominal bloating within a median of 4 weeks after initiating treatment. In contrast, patients in the placebo group achieved decreased abdominal pain, discomfort, and bloating within 6, 7, and 8 weeks, respectively.

Patients taking linaclotide achieved 1 or more additional complete spontaneous bowel movements per week within a median of 2 weeks compared with 4 weeks in the placebo group (P <.0001). Approximately 8.5% (100 of 1178) of patients were late responders to linaclotide within 4-12 weeks with this objective as the threshold.

Those on linaclotide achieved 3 or more complete spontaneous bowel movements within a median of 4 weeks compared with the placebo group who never reached this objective after 12 weeks (P <.0001). Approximately 10.9% (128 of 1178) of patients were late responders with 3 or more spontaneous bowel movements as the threshold.

While not all linaclotide-treated patients responded within the 12-week treatment period, 1 in 6 patients on linaclotide achieved late responses for decreased abdominal pain and 1 in 10 patients achieved late responses for increased complete spontaneous bowel movement frequency.

After comparing subgroups, researchers observed that patients who were women, White, and who had less severe baseline abdominal symptoms were more likely to respond to linaclotide within 4 weeks.

“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,” the study authors wrote. “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.”

Study limitations include heterogeneity of methods and patient populations among the 4 clinical trials used for the posthoc analysis and a lack of generalizability to the real-world disease population due to stringent inclusion criteria for the trials.

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.


Brenner DM, Lacy BE, Ford AC, et al. Linaclotide reduced response time for irritable bowel syndrome with constipation symptoms: Analysis of 4 randomized controlled trials. Am J Gastroenterol. Published online November 16, 2022. doi:10.14309/ajg.0000000000002064