Linaclotide (Linzess) demonstrates significant efficacy in alleviating functional constipation among children with neurodevelopmental disorders, according to a recent analysis presented at the North American Society of Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN) 2024. This finding addresses a critical need for effective treatments in a population often facing multifaceted challenges in managing constipation.
The post-hoc analysis of a pivotal phase 3 trial, which supported the FDA approval of linaclotide for pediatric functional constipation, specifically examined outcomes in children with comorbid neurodevelopmental disorders. These disorders included conditions such as ADHD, ASD, and tic disorders. Hannibal Person, MD, from the University of Washington, highlighted the difficulties in managing functional constipation in these children, emphasizing the importance of this in-depth analysis.
The original phase 3 trial enrolled 330 patients aged 6 to 17 years with functional constipation, randomizing them to either oral linaclotide 72 μg or placebo once daily for 12 weeks. The primary outcome, weekly spontaneous bowel movement frequency, showed significant improvement with linaclotide compared to placebo (P < .0001). The subsequent analysis focused on a subgroup of 57 patients with neurodevelopmental disorders (25 receiving linaclotide, 32 receiving placebo).
Efficacy and Safety in Neurodevelopmental Disorders
The analysis revealed that linaclotide provided a beneficial treatment effect across all efficacy endpoints in children with neurodevelopmental disorders. The improvements in bowel function were consistent with those observed in the overall study population. Importantly, the incidence of diarrhea, a treatment-emergent adverse event, was similar between the linaclotide (4.0%) and placebo (0%) groups in this subgroup, aligning with rates seen with other laxatives.
Adherence and Compliance
An important aspect of the study was the high rate of treatment adherence. Approximately 96% of patients completed 8-12 weeks of treatment, with a compliance rate of 96% or greater for the once-daily oral administration of linaclotide or placebo. Dr. Person noted that this high adherence rate was particularly encouraging, given the potential challenges in medication adherence within this population.
"The fact that the kids did well, just like their peers, was a really great sign," Dr. Person stated. "The other thing is the rate of adherence to the medication...we had a very high rate, greater than 90% of adherence for 8 weeks of treatment, which was fantastic."
These findings suggest that linaclotide is not only effective but also well-tolerated and accepted by children with functional constipation and comorbid neurodevelopmental disorders, offering a valuable treatment option for this challenging patient group.
