Efficacy of botulinum toxin type A (BoNTA) injections for the treatment of faecal incontinence

A recent study suggests that intrarectal botulinum toxin type A (BoNTA) injections are an efficacious treatment for urge faecal incontinence. This study was published in the journal, The Lancet. Gastroenterology & Hepatology.

This phase 3 study was a double-blind, multicentre, randomized trial that included 200 adult patients who had experienced a failure of conservative or surgical treatment or had at least one urgency or faecal incontinence episode per week for a minimum of 3 months. After withdrawals, the patients were randomly assigned in a 1:1 ratio to receive either 200 units of BoNTA (n=96) or an equivalent volume of saline or placebo (n=95) injections. Three months after treatment, the number of episodes of faecal incontinence and urgency recorded in 21-day patient bowel diaries served as the primary endpoint. For the primary analysis, a modified intention-to-treat (mITT) approach was utilized, with adjustment for baseline faecal incontinence and urgency episodes.

At the end of the study, it was observed that in the BoNTA group, the mean number of faecal incontinence and urgency episodes per day, decreased from 1·9 at baseline to 0.8 at 3 months after the injections were administered while in the placebo group, it decreased from 1.4 to 1.0. The trial did not report any serious treatment-related adverse events. The non-serious adverse event (treatment-related or not) that was frequently seen was constipation, seen in 68 patients in the BoNTA group and 38 patients in the placebo group. From the above results, it can be concluded that BoNTA injections are an efficacious treatment for urge faecal incontinence in adult patients.

The efficacy of lubiprostone in the treatment of functional constipation in adolescents and children

A recent study has shown that lubiprostone is effective and has good tolerability as a pharmacotherapy for children and adolescents, offering a potential shift in the treatment approach for pediatric functional constipation (FC). This study’s findings were published in the Journal of Pediatric Gastroenterology and Nutrition.

This single-blinded, randomized controlled trial included 280 patients (aged 8-18 years) with FC. These patients were randomly assigned to receive either a weight-based lubiprostone dose (n = 140) or conventional laxatives (n = 140), which included bisacodyl, lactulose, or sodium picosulfate, for a duration of 12 weeks. Subsequently, a 4-week posttreatment follow-up was carried out.

The lubiprostone group demonstrated an improvement in constipation in 91.4% (128 patients) when compared to 34.3% (48 patients) in the conventional therapy group and persisted even after treatment discontinuation. Additionally, within 48 hours of starting the medication, one quarter of the lubiprostone group experienced their first spontaneous bowel movement. Throughout the last 4 weeks of therapy and the subsequent 4 weeks of follow-up, 75.7% of the lubiprostone group maintained a Bristol stool form of 3 or 4 compared to 35.7% (50 patients) in the conventional therapy group. No life-threatening adverse drug reactions were reported, and no patients discontinued treatment due to adverse effects.

Thus, it can be concluded that lubiprostone may be a well-tolerated and effective pharmacotherapy for children and adolescents, presenting a promising alternative in the management of pediatric functional constipation (FC).

Effectiveness of seladelpar in primary biliary cholangitis patients

A recent study suggests that seladelpar notably decreased pruritus in individuals with moderate to severe pruritus at the baseline. The study’s findings  were published in The New England Journal of Medicine.

In this phase 3, double-blind, placebo-controlled trial, a total of 193 patients (who had an inadequate response to or had a previous medical history of adverse side effects with ursodeoxycholic acid) were randomly assigned in a 2:1 ratio to either receive oral seladelpar at a daily dose of 10 mg or placebo. The primary endpoint of the study was a biochemical response, characterized by an alkaline phosphatase level < 1.67 times the upper limit of normal, showing a reduction of 15% or greater from the baseline, and a normal total bilirubin level by the end of the 12^th month. Key secondary endpoints included the normalization of alkaline phosphatase level at 12^th month  and the change in pruritus numerical rating scale score from baseline to 6^th month among patients with a baseline score of at least 4 (denoting moderate-to-severe pruritus).

A higher proportion of patients in the seladelpar group experienced a biochemical response compared to those in the placebo group (61.7% vs. 20.0%). Additionally, a larger percentage of patients who were treated with seladelpar saw normalization of alkaline phosphatase levels in comparison to those who received a placebo (25.0% vs. 0%). Seladelpar also led to a more significant decrease in pruritus numerical rating scale scores than the placebo (-3.2 vs. -1.7).

Therefore, it can be concluded that the proportion of patients achieving a biochemical response and normalization of alkaline phosphatase was significantly higher with seladelpar compared to placebo. Additionally, seladelpar demonstrated a significant reduction in pruritus for primary biliary cholangitis patients experiencing moderate-to-severe pruritus at the baseline.

Resmetirom for the treatment of NASH with liver fibrosis

According to a recent study, both the 80-mg dose and the 100-mg dose of resmetirom exhibited superior effectiveness compared to the placebo in terms of resolving NASH and improving liver fibrosis by at least one stage. The findings of this study were recently published in The New England Journal of Medicine.

In this phase 3, randomized, controlled trial, patients were assigned randomly, in a 1:1:1 ratio, to receive either 80 mg (n=322) or 100 mg (n=323) of resmetirom once daily, or a placebo (n=321). The two primary endpoints of the study at week 52 included resolution of NASH, which involved a reduction in the nonalcoholic fatty liver disease (NAFLD) activity score by ≥2 points as well as an improvement in fibrosis by at least one stage, with no worsening observed in the NAFLD activity score.

In the 80-mg resmetirom group, 25.9% of the patients achieved NASH resolution without worsening of fibrosis, while in the 100-mg resmetirom group, this was achieved by 29.9% of the patients. In comparison, only 9.7% of the patients in the placebo group achieved the same outcome. Improvement in fibrosis by at least one stage without worsening of the NAFLD activity score was noted in 24.2% of patients in the 80-mg resmetirom group and 25.9% in the 100-mg resmetirom group. In contrast, only 14.2% of patients in the placebo group experienced such improvement.

Thus, it can be concluded that in terms of NASH resolution and improvement in liver fibrosis by at least one stage, both the 80-mg dose and the 100-mg dose of resmetirom showed superiority over placebo.