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).
Moreover, the median time to CSBM response, defined as an increase in CSBM weekly rate of ≥1, was significantly shorter in the two linaclotide groups than the placebo group, 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 patients with 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]
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