Rectal Botox injections improved fecal incontinence, emergency

Botulinum toxin type A (Botox) injections into the rectum reduced episodes of faecal incontinence and urgency, a randomized controlled trial showed.

Among nearly 200 patients in a modified intention-to-treat analysis, the mean number of fecal incontinence and urgency episodes per day in the Botox group decreased from 1.9 at baseline to 0.8 at 3 months after injections compared with a decrease from 1.4 to 1.0 in the placebo group, with a baseline-adjusted group mean difference of -0.51 (95% CI -0.8 to -0.21, Pi=0.0008), reported Anne-Marie Leroi, PhD, of the University Hospital of Rouen in France, and colleagues.

Patients who received the Botox injections also reported greater improvements in quality of life and delayed defecation, as well as a better overall impression of the treatment, compared with patients who received a placebo saline injection, they noted in Lancet Gastroenterology and Hepatology.

The study appears to be the first randomized controlled trial to evaluate the potential of botulinum toxin injections to treat fecal incontinence and urgency, a condition that affects about 8.3 percent of U.S. adults, the authors wrote. Only two previous ones case series and one case report have been reported on these injections for fecal incontinence.

“New treatments are needed for a field that has seen little meaningful therapeutic progress over the past 30 years and has had few sufficiently powered high-quality randomized controlled trials to inform its evidence base,” wrote Charles H. Knowles, MBBChir, PhD, of Queen Mary University of London, in one accompanying article. This trial produced “the largest fecal incontinence treatment effect seen of any comparable placebo-controlled trial,” he noted.

“Although there are some interpretive limitations arising from the established general weakness of gut diaries and the imbalance in the primary outcome measure at baseline, this study represents an important step forward in the field, not only because it may make a new treatment available to patients. but also because it helps challenge a dogma that consistently downplays the importance of the rectum in the pathophysiology of faecal incontinence,” Knowles wrote.

He noted similarities in therapeutic effect with botulinum toxin injections for overactive bladder and concluded “that [botulinum toxin type A] Rectal injection therapy will rapidly gain traction with both physicians and surgeons for patients with a predominantly imperative phenotype who have not responded to first-line therapies and may prefer a low-risk endoscopic therapy to peranal irrigation or the neuromodulation of the sacrum.

The double-blind study included 96 patients (mean age 61.4, 92% female) who were randomized to receive intrarectal injections of 200 units of Botox and 95 patients (mean age 62.1, 92% female) who received intrarectal injections of normal saline as placebo from November 2015 to November 2020. All participants had at least one episode of faecal urgency or incontinence per week for at least 3 months and had previously undergone conservative or surgical treatment in one of eight French specialist hospitals that did not resolved their symptoms.

The researchers defined an urgent episode as “a sudden need to rush to the bathroom to have a bowel movement.”

Leroi and colleagues used the composite endpoint of episodes of combined incontinence and urgency for the sake of achieving statistical power, to ensure that they addressed urgency as a treatment target, and because faecal incontinence alone may not adequately represent emergency.

“Indeed, the inability to postpone defecation often leads to limitations in patients leaving home, with strict planning of access to toilet facilities, as some patients have no or only a few episodes of faecal incontinence,” they wrote.

Each patient received 10 initial injections at various submucosal sites within the rectum from a sclerotherapy needle during flexible sigmoidoscopy, without sedation, and then a final injection at the first injection site to wash out residual fluid. Intervention injections were 1 mL of Botox diluted in saline.

The primary endpoint was assessed using 21-day patient bowel diaries leading up to a 3-month follow-up appointment. At the 3-month visit, there was a 50% or greater reduction in the number of fecal incontinence episodes and urgency episodes per day in 72% of patients in the Botox group versus 46% of those in the placebo group (Pi=0.0001).

A therapeutic effect persisted at 6 months, when the intervention group had an average of 0.38 fewer daily episodes of faecal incontinence and urgency than the placebo group (Pi=0.03). At this follow-up, 76% of Botox patients and 43% of placebo patients found the injection beneficial or helpful, and 76% and 37%, respectively, reported that the injection improved their quality of life (Pi<0.0001 for both). A similar proportion of patients in each group said they would request another injection.

No serious side effects were noted. Constipation, reported by 40% of participants in both groups, was the most common side effect. At 6 months, patients in the placebo group could choose to receive a Botox injection in an open-label extension phase.

They said that some improvement in the placebo group was probably due to a placebo effect: “the well-recognized positive progression of functional digestive symptoms after any therapeutic intervention, even sham.”