Board Review

A 40-year-old man is evaluated in follow-up for irritable bowel syndrome with constipation (IBS-C), which was diagnosed 3 months ago. His IBS symptoms did not respond to a trial of psyllium, which was discontinued owing to bloating. A trial of polyethylene glycol had similar results. He has no other medical problems and takes no other medications.

On physical examination, vital signs are normal. Abdominal examination reveals generalized abdominal tenderness but is otherwise normal.

Which of the following is the most appropriate treatment?

A) Start a bran-based dietary supplement

B) Start bisacodyl

C) Start linaclotide

D) Start rifaximin

Answer: C - Start linaclotide

Objective: Treat irritable bowel syndrome with constipation that is refractory to standard laxative therapy.

Key Point

Linaclotide is FDA approved for the treatment of irritable bowel syndrome with constipation in adults; like lubiprostone, it is second-line therapy for patients whose symptoms have not responded to standard laxative therapy.

The most appropriate treatment is to start linaclotide. This patient's symptoms have not responded to initial trials of two over-the-counter laxatives for treatment of his irritable bowel syndrome with constipation (IBS-C) symptoms. Linaclotide is a synthetic peptide that acts peripherally in the gut and activates guanylate cyclase-C receptors on the enterocytes lining the small bowel and colon. Activation of the guanylate cyclase-C receptors results in increased production of cyclic guanosine monophosphate (cGMP), which in turn activates the movement of chloride ions into the intestinal lumen and promotes passive movement of sodium ions and water in the intestinal lumen. These secretory effects lead to treatment of constipation symptoms. In a multicenter randomized controlled trial (RCT) involving 804 patients with IBS-C, linaclotide significantly improved abdominal and bowel symptoms associated with IBS-C over 26 weeks of treatment. Diarrhea was the most common side effect, prompting discontinuation in 4.5% of patients. Linaclotide has an FDA indication for the treatment of adults with IBS-C and chronic constipation. Linaclotide is not a first-line agent in IBS-C, but it is appropriate for patients whose symptoms persist despite the use of fiber and standard laxatives. Lubiprostone, a chloride channel activator that increases intestinal fluid secretion, can also be used as a second-line agent in patients with IBS-C or chronic idiopathic constipation.

Bran has not shown any benefit compared with placebo in the treatment of IBS-C and is likely to worsen symptoms of bloating.

Bisacodyl has not been assessed for use in IBS-C in any RCTs. Furthermore, the side effect of abdominal cramping associated with bisacodyl is likely to exacerbate this patient's baseline abdominal pain.

Since publication of this question, rifaximin has been approved by the Food and Drug Administration for treatment of irritable bowel syndrome with diarrhea (IBS-D) in adult men and women. Recommended treatment of abdominal pain and diarrhea associated with IBS-D with rifaximin is oral dosing three times a day for 14 days; recurrent symptoms may be retreated with a 14-day treatment course up to two times. Rifaximin continues to have no indication for the treatment of IBS-C, as in this patient, or for mixed IBS.

Chey WD, Lembo AJ, Lavins BJ, et al. Linaclotide for irritable bowel syndrome with constipation: a 26-week, randomized, double-blind, placebo-controlled trial to evaluate efficacy and safety. Am J Gastroenterol.2012 Nov;107(11):1702-12. Link Out