Effect of Age and Age-Defined Menopausal Status on Linaclotide Efficacy and Safety in Adults With Irritable Bowel Syndrome With Constipation or Chronic Idiopathic Constipation: Post Hoc Analyses of Phase 2b/3 Studies.

BACKGROUND: This post hoc study explored the effect of age and age-defined menopausal status on linaclotide efficacy and safety in adults with irritable bowel syndrome with constipation (IBS-C) or chronic idiopathic constipation (CIC). METHODS: Data were pooled from eight randomized, placebo-controlled studies of linaclotide 72 μg (CIC), 145 μg (CIC), or 290 μg (IBS-C). Patients were stratified by age (< 65 years; ≥ 65 years) and female patients by age-defined menopausal status (premenopausal: ≤ 45 years; postmenopausal: > 45 years) as a surrogate for clinically confirmed menopausal status. Efficacy endpoints included change from baseline and time to response in complete spontaneous bowel movement (CSBM) frequency and abdominal symptoms. RESULTS: Linaclotide increased weekly CSBM frequency from baseline versus placebo across age (IBS-C, < 65 years, placebo: 0.8; 290 μg: 2.3; ≥ 65 years, placebo: 0.9; 290 μg: 2.6; CIC, < 65 years, placebo: 0.7; 72 μg: 1.7; 145 μg: 2.0; ≥ 65 years, placebo: 0.9; 72 μg: 1.5; 145 μg: 2.3) and menopausal subgroups. Abdominal symptoms reduced from baseline versus placebo across all subgroups. Median time (weeks) to an increase from baseline in weekly CSBM rate of ≥ 1 was shorter with linaclotide versus placebo across age (IBS-C, < 65 years, placebo: 4.0; 290 μg: 2.0; ≥ 65 years, placebo: 3.0; 290 μg: 2.0; CIC, < 65 years, placebo: 4.0; 72 μg: 3.0; 145 μg: 2.0; ≥ 65 years, placebo: 5.0; 72 μg: 3.0; 145 μg: 1.5) and age-defined menopausal subgroups. CONCLUSION: In this exploratory post hoc analysis, linaclotide was associated with improvements in bowel and abdominal symptoms across age and age-defined menopausal subgroups, with a safety profile consistent with previous studies, suggesting that age and menopausal status did not meaningfully influence treatment outcomes.