Linaclotide reduces response time for patients of irritable bowel syndrome with constipation: Study

Results from pooled analyses of 4 randomized controlled trials suggest that treatment responses with linaclotide occurred in over half of the patients with IBS-C within four weeks of treatment initiation; still, benefits for individual symptoms and complete spontaneous bowel movements (CSBMs) frequency can occur between 4 and 12 weeks.

"A lack of improvement in one symptom does not invalidate the possibility of response for another, underscoring the importance of discussing all symptoms with patients and not assuming uselessness of treatment at four weeks," Darren M. Brenner, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA, and colleagues wrote in their study.

Irritable bowel syndrome is a chronic condition that affects about 3 to 10% of the global population. Recent diagnostic criteria include recurrent abdominal pain that occurred at least one day per week (on average) in the past three months. The changes in bowel function define different subtypes of IBS; evidence indicates that IBS patients with constipation experience more bothersome and frequent abdominal pain than patients with other subtypes.

Because of its heterogeneous pathogenesis, there is no single effective treatment for IBS, and patients with the same symptoms can respond differently to the same treatment.

Given the unpredictable response to treatment and variable symptoms profile, there is a distinct possibility that a medication that might improve symptoms is prematurely discontinued owing to a perceived lack of efficacy, implying that patients cycle through multiple therapies leading to increasing costs and exhaustion of available treatments. Therefore, patients and clinicians may benefit from more information regarding patterns of time to response to individual IBS symptoms.

The post hoc analyses of pooled data from 4 randomized controlled trials aimed to provide clinically relevant data for linaclotide use in patients with IBS-C. In addition to assessing time to response for individual bowel and abdominal symptoms, these analyses assessed the temporal relationship between symptom responses in patients treated with linaclotide vs placebo.

Response time for abdominal symptoms (discomfort, pain, and bloating) and CSBMs are analyzed. The research team pooled time-to-response data from 4 randomized controlled trials. Patients were divided as early responders - ≤4 weeks, late responders - >4–12 weeks or nonresponders.

The authors reported the following findings:

· 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 discomfort, abdominal pain, 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 approximately 1 in 10 patients for CSBM frequency.

· Comparisons of early responders, late responders, and nonresponders for both response definitions indicated that women, Whites, and patients with less severe baseline abdominal symptoms were more likely to respond early.

"Findings from the pooled analyses indicate that over 50% of IBS-C patients treated with linaclotide will experience response for discomfort, abdominal pain, and bloating or CSBM frequency within four weeks of treatment initiation," the authors conclude. "Another 8%–17% showed a response between weeks 5 and 12."

For individual symptoms, time to response differs and is influenced by patient characteristics. A lack of improvement in one symptom does not nullify the possibility of a response in other. This highlights how important it is that clinicians review any benefit across all symptoms with patients and do not assume the futility of treatment at four weeks.

Reference:

Brenner, Darren M. MD1; Lacy, Brian E. MD, PhD2; Ford, Alexander C. MD3,4; Bartolini, Wilmin PhD5,6; Wu, James PhD5; Shea, Elizabeth P. PhD5,7; Bochenek, Wieslaw MD, PhD8; Boinpally, Ramesh PhD8; Almansa, Cristina MD, PhD5,9. Linaclotide Reduced Response Time for Irritable Bowel Syndrome With Constipation Symptoms: Analysis of 4 Randomized Controlled Trials. The American Journal of Gastroenterology ():10.14309/ajg.0000000000002064, November 16, 2022. | DOI: 10.14309/ajg.0000000000002064