Recommendations for pharmacologic management of IBS with diarrhea, constipation

Two new guidelines from the American Gastroenterological Association (AGA) on treatment of irritable bowel syndrome with constipation (IBS-C) and diarrhea (IBS-D) discuss when to use new IBS drugs, when to use older FDA-approved drugs, and when to use over-the-counter drugs.

For IBS-C, the guideline panel gave a strong recommendation for linaclotide (high certainty) and conditional recommendations for tenapanor, plecanatide, tegaserod, and lubiprostone (moderate certainty) and polyethylene glycol laxatives, tricyclic antidepressants, and antispasmodics (low certainty). The panel gave a conditional recommendation against the use of selective serotonin reuptake inhibitors (low certainty).

For IBS-D, the panel gave conditional recommendations for eluxadoline, rifaximin, and alosetron (moderate certainty); loperamide (very low certainty); and tricyclic antidepressants and antispasmodics (low certainty). The panel gave a conditional recommendation against the use of selective serotonin reuptake inhibitors (low certainty).

The guidelines were published June 21 by Gastroenterology and were summarized in the June ACP Gastroenterology Monthly. The following commentary by Xavier Calvet, MD, was published in the ACP Journal Club section of the November Annals of Internal Medicine.

The approach to patients with IBS should consider that neither conventional Western medicine nor other curative practices can provide a universally effective treatment for IBS. Fortunately, major morbidity is extremely rare in IBS; symptoms fluctuate with periods of relative well-being; and a combination of diet, drugs, and less conventional therapies often improve symptoms, although to variable and unpredictable degrees.

The AGA clinical practice guidelines for IBS-C by Chang and colleagues and IBS-D by Lembo and colleagues summarize the evidence on the available pharmacologic treatments and make recommendations for their use. At first sight, the guidelines seem to suggest that we have several effective drugs for IBS-C and IBS-D. A more detailed analysis, however, reveals a less optimistic picture: The best treatments increase the rate of response by only 15% vs. placebo. In addition, drugs often have high costs, and rates of side effects leading to discontinuation vary from 3% to 7%. Enthusiasm declines further when we consider that the primary end point in most studies was rather weak. For IBS-C, a common primary outcome was a 30% reduction in average daily worst abdominal pain scores plus an increase of 1 complete spontaneous bowel movement per week compared with baseline. For IBS-D, a typical primary outcome was a similar rate of pain reduction plus a stool consistency score of <5 on 50% of days.

The effects of different drugs on quality of life (QoL) were reported in the supplementary material. There were remarkable differences in QoL changes among the different drugs, and in a benign disease like IBS, QoL is a very important end point. In IBS-D, rifaximin improved QoL in 240 more patients per 1000 patients vs. placebo; eluxadoline improved QoL in 64 additional patients per 1000. In IBD-C, linaclotide led to an improvement of QoL in 135 per 1000 patients vs. placebo, whereas tenapanor or tegaserod did not improve QoL. The observed differences, however, should be interpreted with caution as direct comparisons between drugs are not available.

These findings informed an algorithm clinical decision-support tool that recommends lifestyle modifications and diet as initial treatment. Recommended first-line pharmacologic treatments are antispasmodics plus either an osmotic laxative for IBS-C or loperamide or bile acid sequestrants for IBS-D. New agents are recommended for second- or even third-line pharmacologic treatment. In addition, I would be wary of prescribing drugs with a risk for life-threatening adverse events (e.g., tegaserod, eluxadoline, or alosetron) in an essentially benign disorder such as IBS.

In conclusion, the new AGA clinical practice guidelines provide updated information on the usefulness and limitations of pharmacologic treatment in IBS. The limited efficacy of drugs reported is consistent with previous knowledge and clinical experience. In this scenario of treatments with low efficacy, it is important to establish a relationship of trust with patients to provide reassurance on the benign, fluctuating, and chronic nature of symptoms and to set clear therapeutic objectives, including preserving functioning, well-being, and QoL. Providing adequate information on the limited efficacy of currently available treatments may help patients to understand and tolerate therapeutic failures. Patients should be empowered to use available treatments according to their symptoms, beliefs, and needs, with the objective of maximizing their QoL.