Treatment with either dose of linaclotide (72 or 145 µg) showed improvements in bowel movement frequency and abdominal symptoms in adults with severe chronic idiopathic constipation (CIC), according to a post hoc pooled analysis of phase III studies presented at DDW 2026.
Using pooled data from four phase III studies, the researchers identified 1,773 adults with severe CIC, defined as zero complete spontaneous bowel movements (CSBMs) per week during the 2-week baseline period. Participants received linaclotide 72 µg (n=319) or 145 µg (n=732) or a placebo (n=722) over a 12-week treatment period. Baseline characteristics were comparable across all treatment groups.
After 12 weeks, both doses of linaclotide were associated with significant improvements in weekly SBM frequency (least squares mean [LSM] differences, 0.84 [72 µg] and 1.61 [145 µg]; p<0.001 for both) and CSBM frequency (0.83 [72 µg] and 1.08 [145 µg]; p<0.001 for both) compared with placebo. [DDW 2026, abstract Mo1756]
Stool consistency also improved significantly in the linaclotide groups compared with the placebo group at 12 weeks (odds ratios [ORs], 0.56 [72 µg] and 0.33 [145 µg]; p<0.001 for both).
Among participants with mild symptoms at baseline, linaclotide-treated patients had significant improvements in straining (ORs, 1.72; p<0.01 [72 µg] and 3.63; p<0.001 [145 µg]) and constipation (ORs, 2.05 and 2.74, respectively; p<0.001 for both) than placebo-treated patients.
Abdominal symptoms, including bloating (ORs, 1.75 [72 µg] and 1.92 [145 µg]; p<0.001 for both) and discomfort (ORs, 1.43; p<0.05 [72 µg] and 1.77; p<0.001 [145 µg]; p<0.001) were also markedly improved with linaclotide as compared with placebo.
Additionally, abdominal pain was significantly improved in the linaclotide 145-µg dosing group (OR, 2; p<0.001), but not in the linaclotide 72-µg dosing group (OR, 1.18).
Similar outcomes were observed in patients with severe symptoms at baseline.
Safety findings indicated that 30.4 percent and 46.2 percent of the patients in the linaclotide 72 and 145 µg groups, respectively, experienced ≥1 treatment-emergent adverse event (TEAE), with diarrhoea (15.4 percent and 14.2 percent) being the most common TEAE.
Overall, the researchers concluded that “these findings highlight the ability of linaclotide to improve both bowel function and abdominal symptoms in severe CIC, a population in which multidimensional symptom burden often drives treatment decisions in clinical practice.”