Novel Therapies in IBS-D Treatment

Abstract

Irritable bowel syndrome (IBS) is a common gastrointestinal disease characterized by abdominal pain and change in bowel habits. IBS diarrhea predominant (IBS-D), which is arguably the most common subset of IBS, is also associated with rectal urgency, increased frequency, abdominal bloating, and loose to watery stools. Current treatments for diarrhea include mu-opioid agonists (i.e., loperamide, lomotil) and bile acid sequestrants (i.e., cholestyramine) while treatments for abdominal pain include antispasmodics (i.e., hyoscyamine, dicyclomine) and tricyclic antidepressants (i.e., amitriptyline). There are currently 3 FDA-approved treatments for IBS-D, which have been shown to improve both abdominal pain and diarrhea. Alosetron was initially approved by FDA 2000; however, its use is now limited to women with severe IBS-D symptoms refractory to other treatment. Eluxadoline, a mixed mu-opioid agonist, and rifaximin, a broad spectrum gut specific antibiotic, were both FDA approved in 2015. Eluxadoline has been shown to relieve abdominal pain and stool consistency in appropriate candidates. While large trials already showed the efficacy of rifaximin in treating non-constipated IBS for bloating, stool consistency, and abdominal pain, the recent TARGET 3 trial demonstrates that retreatment is also effective. While these new treatments significantly expand options for patients suffering from IBS-D, there is likely to remain a need for additional safe and effective therapies.

Randomised clinical trial: exploratory phase 2 study of ONO‐2952 in diarrhoea‐predominant irritable bowel syndrome

“…10 There are currently only three approved pharmacological treatments for IBS-D, which have been shown to improve both abdominal pain and diarrhoea. 11 The 5-HT 3 antagonist alosetron was initially approved in 2000, but due to serious gastrointestinal adverse effects, its use is now limited to women with severe IBS-D symptoms that are refractory to other treatments. Eluxadoline (a mixed l-opioid receptor agonist and d-opioid receptor antagonist) and rifaximin (a broad-spectrum, non-absorbable, gut-specific antibiotic) were both approved in 2015.…”

“…Eluxadoline (a mixed l-opioid receptor agonist and d-opioid receptor antagonist) and rifaximin (a broad-spectrum, non-absorbable, gut-specific antibiotic) were both approved in 2015. 11,12 Although these new treatments have expanded the treatment options available for IBS-D, there remains a need for further effective and well-tolerated therapies. 11 Translocator protein 18 kDa (TSPO) is a five-domain transmembrane protein that is highly expressed in steroid-producing tissues, including the glial cells within the brain.…”

“…11,12 Although these new treatments have expanded the treatment options available for IBS-D, there remains a need for further effective and well-tolerated therapies. 11 Translocator protein 18 kDa (TSPO) is a five-domain transmembrane protein that is highly expressed in steroid-producing tissues, including the glial cells within the brain. [13][14][15][16] TSPO ligands can modulate the synthesis of neurosteroids that act as allosteric modulators of excitatory and/or inhibitory neurotransmitter receptors.…”

Inhibition of CFTR‐mediated intestinal chloride secretion as potential therapy for bile acid diarrhea

“…For IBS-D, in which BAD is likely involved in pathogenesis in more than one-third of patients (1,2), FDA-approved therapies include the 5-hydroxytryptamine type 3 antagonist alosetron, the mixed m opioid receptor agonist eluxadoline, and the broad-spectrum gut-specific antibiotic rifaximin. Other commonly used therapies for IBS-D include loperamide, bile acid sequestrants, antispasmodics, and tricyclic antidepressants (33)(34)(35). Some of these therapies are associated with significant side effects such as ischemic colitis with alosetron and pancreatitis with eluxadoline (35).…”

“…Other commonly used therapies for IBS-D include loperamide, bile acid sequestrants, antispasmodics, and tricyclic antidepressants (33)(34)(35). Some of these therapies are associated with significant side effects such as ischemic colitis with alosetron and pancreatitis with eluxadoline (35).…”