Linaclotide improves rate of bowel movements, consistency in children with constipation
Click Here to Manage Email Alerts
Key takeaways:
- Once-daily linaclotide improved weekly spontaneous bowel movements from 1.16 to 3.41 during the 12-week intervention.
- Treatment also improved stool consistency, straining and overall abdominal bloating.
Treatment with once-daily linaclotide was well-tolerated and resulted in significant improvement in spontaneous bowel movements and stool consistency vs. placebo among children with functional constipation, researchers reported.
“Linaclotide is a guanylate cyclase C agonist acting on the luminal surface of the intestinal epithelium and, at the time of this study, was approved in the USA for the treatment of adults with chronic idiopathic constipation and irritable bowel syndrome with predominant constipation, but was not approved for use in children,” Carlo Di Lorenzo, MD, chief of the division of gastroenterology, hepatology and nutrition at Nationwide Children’s Hospital, and colleagues wrote in The Lancet Gastroenterology & Hepatology.
They continued, “As sustained efficacy had been shown with linaclotide treatment in adults with chronic idiopathic constipation and IBS with predominant constipation, linaclotide had potential to be a therapeutic option to treat symptoms of functional constipation in the pediatric population.”
In a randomized, multicenter phase 3 trial, 328 children (median age, 11 years; 55% girls) with functional constipation received either oral linaclotide 72 µg (n = 164) or placebo (n = 164) once daily for 12 weeks. The primary efficacy endpoint was change from baseline (CFB) in spontaneous bowel movement (SBM) frequency per week; the secondary endpoint was CFB in stool consistency.
According to results, 293 patients (89%) completed a 12-week treatment period (linaclotide group, n = 148; placebo group, n = 145). The mean SBM frequency rate increased from 1.28 per week at baseline to 2.29 per week in the placebo group and from 1.16 per week to 3.41 per week in the treatment group. Patients treated with linaclotide had a “significantly higher” least-squares mean CFB in SBM frequency rate compared with placebo (2.22 vs. 1.05 SBMs per week; difference = 1.17; 95% CI, 0.65-1.69).
In addition, researchers reported that the treatment group had “significant improvement” compared with the placebo group in least-squares mean CFB in stool consistency (1.11 vs. 0.69; difference = 0.42; 95% CI, 0.21-0.64), as well as improvement in straining with bowel movements (difference = –0.44; 95% CI –0.65 to –0.23) and overall abdominal bloating (difference = –0.16; 95% CI, –0.3 to –0.02).
Treatment-related adverse events occurred among 5% of patients in the treatment group and 3% in the placebo group, the most frequent of which were diarrhea in the treatment group (4%) and COVID-19 in the placebo group (3%). No deaths were reported.
Researchers noted that since the conclusion of the study, once-daily linaclotide has been approved by the FDA for treatment of functional constipation in children aged 6 to 17 years.
“Linaclotide was efficacious and well-tolerated in children with functional constipation, suggesting that it could safely alleviate some of the symptom burden in pediatric patients,” Di Lorenzo and colleagues wrote. “Further studies evaluating increased dosing regimens for older children will be important.”
They added, “The data from this study will inform counseling by clinicians on the use of linaclotide in children with functional constipation, with results that can be further validated in long-term extension studies.”
Collapse
Click Here to Manage Email Alerts