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Review highlights novel treatments for chronic constipation
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A review recently published in JAMA highlighted the development of novel treatments for chronic constipation while underscoring the importance of evaluating refractory patients for functional defecation disorders.
To provide an overview of recent developments in the management of constipation, Arnold Wald, MD, from the division of gastroenterology and hepatology at University of Wisconsin School of Medicine and Public Health, identified 21 peer-reviewed studies and 12 reviews or meta-analyses published through October 2015 to support his conclusions.
Arnold Wald
Laxatives and promotility agents for chronic idiopathic constipation
The majority of population surveys indicate the medical management of chronic idiopathic constipation is “suboptimal,” and thus, there is an “intense interest in developing drugs that stimulate gastrointestinal motility via the serotonin4 receptor (prokinetics) as well as agents that directly stimulate intestinal secretion to increase stool water content (intestinal secretogogues),” Wald wrote.
There is extensive data confirming the efficacy of the high-affinity serotonin4 receptor agonist Resolor (prucalopride, Movetis), which is widely used in Europe for chronic idiopathic constipation but not yet approved in the U.S. However, Wald highlighted a study demonstrating the noninferiority of prucalopride vs. polyethylene glycol 3350-electrolyte, and an accompanying editorial that suggested future studies should compare newer constipation treatments to established and inexpensive laxatives.
“Comparator studies may become increasingly important in deciding which new drugs should be available as first-line agents for most patients with [chronic idiopathic constipation,” he wrote, adding that until such data become available, treatment should be guided by cost considerations and potential adverse effects.
The efficacy of the intestinal secretogogues Amitiza (lubiprostone, Sucampo), Linzess (linaclotide, Ironwood) and plecanatide (Synergy Pharmaceuticals) for chronic idiopathic constipation and irritable bowel syndrome with constipation (IBS-C) was also highlighted. Wald concluded that these agents are likely to “remain a second-tier option for [chronic idiopathic constipation] but may have a more prominent role in IBS-C, for which there are fewer alternatives to treatment.”
Wald also emphasized that physician underuse of stimulant laxatives like senna and bisacodyl is unwarranted, as evidence shows they are safe and effective and do not have the potential for addiction when used appropriately.
New approaches to treating opioid-induced constipation
A major point in Wald’s review is that the development of peripherally restricted µ-opiate receptor antagonists is “a major advance” in the treatment of opioid-induced constipation. Efficacy data demonstrating superiority over placebo are available for injectable Relistor (methylnaltrexone, Salix) which is approved by the FDA for patients taking opioids for chronic noncancer pain, and more recently, Movantik (naloxegol, AstraZeneca) an oral agent which was approved in September 2014.
These agents are a more biologically plausible approach to [opioid-induced constipation], which is to administer an effective opioid receptor antagonist that will not counteract the benefits of pain reduction obtained by opioid agents,” as would naltrexone and naloxone, Wald wrote.
Changes in diagnosing functional defecation disorders
Many patients with chronic idiopathic constipation who have poor or no response to conventional therapy have a functional defecation disorder. “An important shift in the algorithm for diagnostic testing” recently proposed by the AGA recommends that such patients undergo anorectal manometry with balloon expulsion testing without a colon transit study to identify a functional defecation disorder, Wald wrote. “If patients with dyssynergic defecation respond clinically to biofeedback, colon transit testing is not necessary.”
Diagnosing this disorder is important so patients can receive effective treatment, he concluded. “Biofeedback is the preferred treatment for dyssynergic defecation in adults, based upon three randomized clinical trials comprising 370 patients that showed a clear-cut superiority of biofeedback against comparator groups.” – by Adam Leitenberger
Disclosures: Wald reports advisory relationships with Takeda Sucampo, Ironwood, Actavis, Entera Health and Forest Laboratories.
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