A post hoc analysis of linaclotide in pediatric patients with functional constipation and neurodevelopmental disorders.

OBJECTIVES

Functional constipation (FC) is common in children with comorbid neurodevelopmental disorders (NDD) and its optimal treatment may be challenged by adherence and medication tolerability issues in this population. We assessed the efficacy and safety of linaclotide in pediatric patients with FC and NDD.

METHODS

This post hoc analysis of a Phase 3, randomized, placebo-controlled study assessed oral linaclotide 72 µg once daily for 12 weeks in patients aged 6-17 years with FC and NDD. The primary endpoint was change from baseline (CFB) in weekly spontaneous bowel movement (SBM) frequency. In efficacy comparisons, an absolute standardized mean difference (SMD) > 0.2 was considered indicative of a treatment difference.

RESULTS

In this analysis of 57 pediatric patients (linaclotide n = 25; placebo n = 32), 91% had attention-deficit/hyperactivity disorder; other NDDs included autism spectrum disorder, tic disorders, and sensory processing disorders. CFB in weekly SBM frequency over 12 weeks was greater with linaclotide versus placebo (2.09 vs. 0.59, respectively; SMD 0.688). Linaclotide was also associated with greater improvements relative to placebo in stool consistency (CFB 1.37 vs. 0.55, respectively) and straining score (CFB -0.98 vs. -0.59). Most patients (≥96%) achieved ≥80% dosing compliance with once-daily administration of linaclotide or placebo. Linaclotide was well tolerated, with a safety profile consistent with that reported previously.

CONCLUSIONS

In children with FC and comorbid NDD, linaclotide 72 µg once daily was associated with improved constipation outcomes, high adherence, and a well-tolerated safety profile, similar to that seen in the overall study population.

TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT04026113 (https://clinicaltrials.gov/study/NCT04026113).