Safety and efficacy of linaclotide in treating functional constipation in paediatric patients

According to a recent study, linaclotide has proven to be an effective and well-tolerated remedy for functional constipation in pediatric patients. This study’s findings were published in the journal, Lancet. Gastroenterology & hepatology.

In this double-blind, randomised,  placebo-controlled, phase 3 study, patients aged 6-17 years were randomly assigned to receive either oral linaclotide 72 μg [n=166] or placebo [n=164] once daily for 12 weeks. The study's primary efficacy endpoint was the change from baseline (CFB) in the frequency rate of spontaneous bowel movements (SBM) per week over a twelve-week period. The change from baseline in stool consistency during the treatment period was the secondary efficacy endpoint. Efficacy and safety were analyzed in all patients who received at least one dose of the study intervention.

The mean frequency rate for SBMs was 1·28 SBMs per week (SD 0·87) with placebo and 1·16 SBMs per week (0·83) with linaclotide at baseline. This rate increased to 2·29 SBMs per week (1·99) with placebo and 3·41 SBMs per week (2·76) with linaclotide during the intervention. Patients treated with linaclotide demonstrated a significant increase in SBM frequency [least-squares mean (LSM) CFB 2·22 SBMs per week (SE 0·19)] compared to those on placebo [LSM CFB 1·05 SBMs per week (0·19)]. Additionally, linaclotide demonstrated a notable improvement in stool consistency compared to the placebo group [LSM CFB 1.11 (SE 0.08) versus 0.69 (0.08)]. Based on the above results, it can be concluded that linaclotide is an efficacious and well-tolerated treatment for functional constipation in paediatric patients.

3 L split-dose PEG regimen superior to 2 L PEG regimen for colonoscopic bowel preparation

A recent study demonstrated that 3 L split-dose polyethylene glycol (PEG) is superior to 2 L polyethylene glycol for colonoscopic bowel preparation in individuals with relatively high BMI. This study was published in the journal, BMC Gastroenterology.

This was a multicenter randomized controlled trial that included 710 individuals with high BMIs (≥ 24 kg/m2), who were scheduled to undergo colonoscopy. The participants were randomly assigned into the 3 L split-dose polyethylene glycol (PEG) group (n=353) and the 2 L PEG group (n=357).  The primary outcome of the study was the rate of adequate bowel preparation, and the secondary outcomes included the Boston Bowel Preparation Scale (BBPS) score, polyp detection rate, cecal intubation rate, and adverse reactions during bowel preparation. Additionally, the study had exploratory subgroup analyses for adequate bowel preparation.

After enrollment, 15 participants did not undergo colonoscopy, only 345 participants received 3 L split-dose PEG regimen, and 350 participants received 2 L PEG regimen for colonoscopic bowel preparation. It was shown that the rate of adequate bowel preparation was superior in the 3 L split-dose PEG regimen (81.2%) compared to the 2 L PEG regimen (74.9%). Additionally, it was found that the BBPS score (6.71±1.15 vs. 6.37±1.31) and the rate of polyp detection (62.0% vs. 52.9%) were better with the 3 L split-dose PEG regimen compared to the 2 L PEG regimen. In the subgroup analysis, the 3 L split-dose PEG regimen performed better than the 2 L PEG regimen in the overweight individuals (BMI 25-29.9 kg/m2).

These findings suggest that a 3 L split-dose PEG regimen is superior to a 2 L PEG regimen for colonoscopic bowel preparation in individuals with high BMI (25-29.9 kg/m2).

Antibiotic prophylaxis results in lower risk of infectious complications before ERCP in patients with biliary obstruction

A recent study suggests that incidence of postendoscopic retrograde cholangiopancreatography (ERCP) infections was significantly lower with antibiotic prophylaxis in patients with biliary obstruction. The study's findings were published in The American Journal of Gastroenterology.

This double-blind, placebo-controlled, randomized trial included 378 patients who were randomly assigned in a 1:1 ratio to receive either a single dose of 1 g intravenous cefoxitin (n=189) or normal saline (n=189; placebo), 30 minutes before undergoing ERCP. The incidence of infectious complications after ERCP comprised the primary outcome of this trial.

At the end of the study, it was found that the risk of infectious complications after ERCP was 2.8% and 9.8% in the antibiotic prophylaxis group and placebo group, respectively. The incidence rates of bacteremia in the antibiotic prophylaxis and placebo groups were 2.3% and 6.4%, respectively. Finally, the incidence rate of cholangitis was 1.7% in the antibiotic prophylaxis group and 6.4% in the placebo group.

Based on the above results, it can be concluded that before ERCP, antibiotic prophylaxis resulted in a significantly lower risk of infectious complications, especially cholangitis, in patients with biliary obstruction.

Risankizumab is safe and effective in patients with Crohn's disease

A recent study found that risankizumab, an anti-interleukin-23 antibody is safe and effective in patients with moderate-to-severe Crohn’s disease. This study’s findings were published in the Journal of Gastroenterology and Hepatology.

This was a post hoc sub analysis of the global phase 3 ADVANCE, MOTIVATE, and FORTIFY studies. ADVANCE and MOTIVATE were double-blind, placebo-controlled, phase 3 induction studies that included a total of 198 patients who had previously experienced intolerance or inadequate response to biologic (MOTIVATE) or a conventional therapy (ADVANCE). The participants were randomized to receive intravenous risankizumab (600 or 1200 mg) or placebo at weeks 0, 4, and 8. The clinical responders to risankizumab entered the placebo-controlled maintenance withdrawal study (FORTIFY). Patients were re-randomized to receive subcutaneous risankizumab (180 or 360 mg) or placebo (withdrawal) every 8 weeks for 52 weeks.

Among 198 patients in the induction studies, the rates of clinical remission and endoscopic response at week 12 were achieved by 61.4% and 40.0% of patients in the risankizumab 600 mg group, 59.5% and 35.8% of patients in the risankizumab 1200 mg group, and 27.3% and 9.1% of patients in the placebo group, respectively. At week 52, among 67 patients who entered the maintenance study, clinical remission and endoscopic response rates were achieved by 57.1% and 52.4% of patients in the risankizumab 180 mg group, 75.0% and 40.0% of patients in the risankizumab 360 mg group, and 53.8% and 34.6% of patients in the placebo (withdrawal) group. Additionally, it was observed that fistula closure was observed in 28.6% (induction) and 57.1% (maintenance) of patients with risankizumab treatment.

Based on the above findings, it may be concluded that risankizumab was effective and well tolerated in patients with Crohn's disease.