New Options On The Horizon For IBS-D

A 21-year-old female college junior entered my office and sat down. I asked her how she was doing and she replied,
“My IBS is a 24/7 living nightmare. I have to monitor everything I eat, where the nearest bathroom is, how long the car or bus ride will be, and of course avoid flying at any cost.” After a short pause she continued, “If that’s not enough, my classmates and professors always make sure the first row seat next to the exit door is saved for me, and I am constantly being asked about the location of toilets all over the whole campus … oh you really don’t want to know what happens during my exams.” At this point, she was tearful and I reached out and handed her a tissue.

The prevalence of irritable bowel syndrome (IBS) is about 15 percent of the general global population. The main symptoms include abdominal pain or discomfort (relieved by defecation) and disordered bowel function. Currently, IBS is diagnosed using Rome criteria (Rome IV was released in May 2016) and subclassified according to predominant stool patterns as either constipation, diarrhea, mixed type or unclassified. About 35 to 40 percent of patients with IBS have diarrhea-predominant bowel symptoms. IBS-D is associated with impairment in health-related quality of life, places a considerable financial burden on society because of reduced work productivity and increases the use of health-related resources.1,2

The postulated pathophysiological factors of IBS-D include: dietary effects on gut permeability and microbiota, alterations in central nervous system innervation and processing of GI-tract stimulation with an increased number of colonic mast cells (leading to reduced pain thresholds throughout the GI system) and disruptions in serotonin signaling with a greater number of serotonin-positive enterochromaffin cells in the crypt epithelium, leading to increased number of colonic contractions, accelerated transit and alterations in small bowel motor function. In addition, one quarter of patients meeting accepted criteria for IBS-D have bile acid malabsorption.35

When we discuss diagnostic testing for IBS-D it is important to emphasize that extensive diagnostic testing in the absence of alarm symptoms is unnecessary and should be avoided; hence, stick to Rome criteria and you will be OK.

Until recently, the traditional treatment for IBS-D included dietary and lifestyle modifications (low FODMAP, gluten-free, low-carb diets), probiotics (B. infantis), antidiarrheal agents (loperamide), and alosetron (serotonin 5HT3 receptor antagonist), which is currently available only for females under a risk management program. Antispasmodics (dicyclomine and hyoscyamine) and peppermint oil relieve muscle contractions without really affecting the diarrhea and are worth a try as an addition to treatment but not as a sole treatment. Colesevelam (bile acid sequestrant) increases stool consistency and decreases number of bowel movements in IBS-D patients with bile acid malabsorption. Additionally, the role of fecal transplants in Clostridium difficile treatment is currently promising, yet its role in IBS-D is still investigational and thus far not part of our regimen.

In 2015, FDA approved two drugs (rifaximin and eluxadoline) that significantly broaden the potential treatment available for patients with IBS-D, thus significantly adding to the current therapeutic options for IBS-D patients.

Rifaximin (nonsystemic antibiotic) 550 mg given three times daily for two weeks significantly improved symptoms at two and four weeks post treatment (probably hanging in there almost up to 10 weeks) in the TARGET 1 and 2 studies. TARGET 3 verified that it is efficacious and safe (slim chance of Clostridium difficile) to re-treat at least two more times (in 10 week intervals).6

Eluxadoline, a mixed mu opioid agonist and delta opioid antagonist (75,100mg twice-daily), significantly improved stool consistency, urgency and frequency for up to six months compared to placebo in a multicenter study. It is important to emphasize that it should not be given to patients with a history of bile duct obstruction, sphincter of Oddi dysfunction, pancreatitis, alcoholism or alcohol abuse.7

I believe that traditional therapies continue to play a role in treatment of IBS-D. Additionally, with our greater understanding of the mechanisms in IBS-D, recent new drugs add to our available treatment and help complement other therapies to improve symptoms and quality of life in patients with IBS-D.

 

Dr. Schey has no conflicts to disclose.

References

1. Lovell RM, Ford AC. Global prevalence of and risk factors for irritable bowel syndrome: a meta-analysis. Clin Gastroenterol Hepatol. 2012; 10(7):712–721.

2. Peery AF, Dellon ES, Lund J, et al. Burden of gastrointestinal disease in the United States: 2012 update. Gastroenterology 2012;143:1179–1187.

3. Distrutti E, Monaldi L, Ricci P, Fiorucci S. Gut microbiota role in irritable bowel syndrome: new therapeutic strategies. World J Gastroenterol. 2016;22(7):2219–2241

4. An S, Zong G, Wang Z, Shi J, Du H, Hu J. Expression of inducible nitric oxide synthase in mast cells contributes to the regulation of inflammatory cytokines in irritable bowel syndrome with diarrhea. Neurogastroenterol Motil 2016.

5. Slattery SA, Niaz O, Aziz Q, Ford AC, Farmer AD. Systematic review with meta-analysis: the prevalence of bile acid malabsorption in the irritable bowel syndrome with diarrhoea. Aliment Pharmacol Ther 2015;42(1):3–11.

6. Pimentel M, Lembo A, Chey WD, et al. Rifaximin therapy for patients with irritable bowel syndrome without constipation. N Engl J Med. 2011;364:22–32.

7. Lembo AJ, Lacy BE, Zuckerman MJ, Schey R, Dove LS, Andrae DA, Davenport JM, McIntyre G, Lopez R, Turner L, Covington PS. Eluxadoline for irritable bowel syndrome with diarrhea. N Engl J Med. 2016 Jan 21;374(3):242–53.

One comment

  • Thanks for this piece–represents important progress in thinking on treatment of IBS. But for the millions of us who have SIBO-related IBS, as you rightly say, we want more research and a cure, not symptom management!

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