Pooled data support linaclotide for IBS-C irrespective of age

Treatment with linaclotide significantly improved abdominal symptoms and the frequency of complete spontaneous bowel movements (CSBMs) among adult and elderly patients with irritable bowel syndrome with constipation (IBS-C), according to the pooled analysis of three phase III trials presented at DDW 2024.

Linaclotide is US FDA-approved for the treatment of adults with IBS-C. However, as previous studies have shown age-related differences in IBS-C symptoms, the researchers conducted a post hoc analysis of pooled data from three phase III trials (LIN-MD-31, MCP-103-302, and MCP-103-3121) to assess the effect of linaclotide on different age groups.

The study included patients aged <65 (n=2,044) and ≥65 years (n=152) with IBS-C who received linaclotide 290 µg once daily or placebo during the first 12 weeks of treatment. The participants were stratified according to age group: <65 years (n=1,028 [linaclotide] and n=1,016 [placebo]) and ≥65 years (n=73 [linaclotide] and n=79 [placebo]). [DDW 2024, abstract Tu1653]

At week 12, the <65 years age group on linaclotide achieved significant improvements in abdominal pain, discomfort, and bloating severity scores (least squares [LS] mean change from baseline, -2.5 vs -1.5, -2.6 vs -1.6, and -2.5 vs -1.5, respectively; p<0.001 for all) compared with those treated with placebo.

Similarly, those aged ≥65 years showed substantial improvements in abdominal symptom scores with linaclotide than those on placebo (LS mean change from baseline, -2.3 vs -1.5; p=0.0020 [pain]; -2.5 vs -1.5; p=0.0012 [discomfort]; and -2.4 vs -1.3; p=0.0001 [bloating]).

Additionally, CSBM frequency was significantly increased in the linaclotide groups vs the placebo group at week 12 (LS mean change from baseline, 2.3 vs 0.9 [<65 years] and 3.2 vs 1.0 [≥65 years]; p<0.0001 for both).

The median time to CSBM response, defined as an increase in CSBM weekly rate of ≥1, was significantly shorter with linaclotide than placebo, both in the <65-year (2 vs 4 weeks; p<0.0001) and the ≥65-year groups (2 vs 3 weeks; p=0.0165), as was the median time to abdominal symptom response, defined as a reduction in abdominal pain, discomfort, and bloating score of ≥30 percent.

However, the incidence of diarrhoea was higher with linaclotide relative to placebo (15.4 vs 2.3 percent [<65 years] and 16 percent vs 6.3 percent [≥65 years]), which was mostly mild to moderate in severity, the researchers noted.

“Treatment-emergent adverse events were similar in both age groups and were consistent with the known safety profile of linaclotide in IBS-C,” said the researchers.

“Overall, these findings suggest that linaclotide was effective and well tolerated in adult patients with IBS-C, irrespective of age,” they concluded.

Linaclotide is an important addition to the therapeutic armament for IBS-C and chronic constipation. [United European Gastroenterol J 2013;1:7-20]