S2949 Exploring the Efficacy and Safety of Linaclotide in Pediatric Patients of Functional Constipation and Irritable Bowel Syndrome With Constipation: A Meta-Analysis of Randomized Control Trials

Introduction: Functional constipation (FC) and irritable bowel syndrome with constipation (IBS-C) are characterized by infrequent, painful, or difficult defecation, often accompanied by fecal incontinence and abdominal discomfort, whereas IBS-C is a gut–brain interaction disorder with recurrent abdominal pain and altered bowel habits. This study aims to evaluate the efficacy and safety of linaclotide for pediatric FC and IBS-C. Methods: PubMed (Medline), EMBASE, and Google Scholar were searched for randomized controlled trials (RCTs) with children suffering from FC and IBS-C. This study used Review Manager and forest plots for visual display. Random effects models were used for this meta-analysis (RRs with 95% CIs) and (SMD with 95% CIs). Risk of bias was assessed using the Cochrane Risk of Bias Tool 2.0. Results: Out of 1,653 identified records, 3 RCTs (309 patients) met the inclusion criteria. Linaclotide showed no statistically significant improvement over placebo in overall CSBMs (SMD = 0.01 [-0.19, 0.20], P = 0.94), abdominal pain (SMD = 0.12 [-0.07, 0.32], P = 0.21), or bloating (SMD = 0.14 [-0.05, 0.34], P = 0.14). However, it significantly improved stool consistency (SMD = 0.52 [0.31, 0.72], P < 0.00001) and reduced straining severity (SMD = -0.29 [-0.49, -0.09], P = 0.004), particularly with higher doses. Adverse events (TEAEs and TRAEs) did not significantly differ between linaclotide and placebo groups. Heterogeneity was low across most outcomes. Conclusion: Linaclotide improves stool consistency and reduces straining severity in pediatric FC and IBS-C, particularly at higher doses. However, it does not significantly enhance bowel movement frequency, complete spontaneous bowel movements, or alleviate abdominal pain. Safety assessments indicate no significant increase in adverse events compared to placebo. Overall, linaclotide may be beneficial for stool consistency but has limited impact on other symptoms.