Linaclotide improves bowel movement frequency in children with functional constipation

Once-daily treatment with linaclotide, a guanylate cyclase C agonist, significantly improved the frequency of spontaneous bowel movements (SBMs) in paediatric patients with functional constipation, according to a recent study.

The researchers conducted a double-blind, placebo-controlled, phase III trial involving 330 paediatric patients aged 6–17 years (55 percent female) diagnosed with functional constipation who were recruited from 64 hospitals across seven countries. Participants were randomly assigned to receive either oral linaclotide 72 µg (n=166) or placebo (n=164) once daily for 12 weeks. All individuals were stratified according to age group: 6–11 years (n=181) and 12–17 years (n=147).

During the 12-week treatment period, patients treated with linaclotide achieved a significant improvement in SBM frequency compared with those treated with placebo (least square mean [LSM] change from baseline, 2.22 vs 1.05 SBMs per week; p<0.0001). [Lancet Gastroenterol Hepatol 2024;doi:10.1016/S2468-1253(23)00398-9]

The mean weekly SBM frequency increased from 1.16 at baseline to 3.41 at week 12 in the linaclotide group and from 1.28 to 2.29 in the placebo group.

Significantly more linaclotide recipients also experienced an SBM within 24 hours (30 percent vs 21 percent; p=0.043) or 48 hours (57 percent vs 38 percent; p=0.0009) after their first dose than placebo recipients.

Stool consistency also significantly improved in the linaclotide group compared with the placebo group at week 12 (LSM change from baseline, 1.11 vs 0.69), with a difference of 0.42 between the treatment groups (p=0.0001).

Taken together, linaclotide showed significantly better efficacy than placebo for both primary and secondary endpoints in both stratified age groups (6–11 and 12–17 years), although the difference was numerically greater in the younger group, said the researchers.

Additional efficacy endpoints

At week 12, patients who received linaclotide had a significantly greater improvement in two bothersome functional constipation symptoms, specifically complete SBM frequency and straining with bowel movements (LSM change from baseline, 1.85 vs 0.90 and -1.19 vs -0.75, respectively; p<0.0001 for both), compared with those who received placebo.

A significant improvement in abdominal bloating was also observed with linaclotide relative to placebo (LSM change from baseline, -0.51 vs -0.35; p=0.027). However, linaclotide did not improve abdominal pain or faecal incontinence episodes, the researchers noted.

“[Nevertheless,] the additional data showing improvements in stool consistency, complete SBM frequency, and straining suggest that linaclotide might address a range of symptoms associated with functional constipation in paediatric patients aged 6–17 years, not just SBM frequency,” said the researchers.

“Overall, linaclotide is an efficacious and well-tolerated treatment for functional constipation in paediatric patients and has been approved by the US FDA for this indication,” the researchers noted.