Efficacy and Safety of Linaclotide in Pediatric Patients of Functional Constipation: A Meta-analysis of Randomized Controlled Trials.

OBJECTIVE: To evaluate the efficacy and safety of linaclotide in children with functional constipation (FC) by synthesizing evidence from randomized controlled trials (RCTs). DATA SOURCES: A systematic search of PubMed, Scopus, Cochrane Central Register of Controlled Trials, and Google Scholar was conducted from inception through December 2024. The protocol was registered in PROSPERO (CRD420251018285), and the review was performed according to PRISMA guidelines. STUDY SELECTION AND DATA EXTRACTION: RCTs comparing linaclotide with placebo in children (<18 years) with FC were included. Two reviewers independently screened studies, extracted data, and assessed risk of bias using the Cochrane RoB 2 tool. Certainty of evidence was evaluated using the GRADE framework. DATA SYNTHESIS: Three RCTs involving 309 pediatric patients were included. Random-effects models demonstrated significant improvements with linaclotide in stool consistency (MD = 0.56, 95% CI, 0.27-0.86; P = .0001) and reduction in straining (MD = -0.26, 95% CI, -0.42 to -0.10; P = .001). No significant effects were observed for spontaneous bowel movement frequency, complete spontaneous bowel movement frequency, or abdominal pain. Treatment-related adverse events were more frequent with linaclotide (relative risk [RR] = 2.93, 95% CI, 1.27-6.77), mainly due to increased diarrhea (RR = 3.81, 95% CI, 1.48-9.82). RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Linaclotide may provide symptom relief for selected children with FC, particularly those with hard stools and straining despite conventional therapy. Clinicians should counsel families regarding diarrhea risk and monitor tolerability, while recognizing the limited long-term pediatric evidence. CONCLUSIONS: Linaclotide improves stool consistency and reduces straining in pediatric FC but does not consistently improve bowel frequency or global symptom resolution. Its safety profile is generally acceptable, although diarrhea is a notable adverse effect. Further long-term, independently funded trials are needed to define its optimal role in clinical practice.