Evaluating the functional net value of pharmacologic agents in treating irritable bowel syndrome.

Abstract

BACKGROUND:

The recent FDA provisional endpoint incorporates a one-tailed measure of improvement for IBS based on the underlying motility complaint. However, motility exists along a spectrum. Patients may experience diarrhoea resulting from therapy for their constipation-predominant IBS (IBS-C) or constipation during treatment for diarrhoea-predominant IBS (IBS-D), but still meet a unidirectional motility-based FDA endpoint.

AIM:

To weigh the reported efficacy of existing therapies based on patient-reported outcomes with negative intestinal side effects in controlled clinical trial data.

METHODS:

We analysed the difference between 'attributable risk' of efficacy based on number needed to treat (NNT) in the literature and percentage of adverse events (AE) of opposite intestinal complaints in placebo-controlled trials identified through a literature search of IBS trials. This calculation was coined 'functional net value' (FNV) or net benefit of the given drug.

RESULTS:

For treating IBS-C, lubiprostone caused diarrhoea in excess of placebo in 3.9% of patients, leading to a FNV of 3.9 percentage units. Linaclotide caused diarrhoea in 15.3% resulting in negative FNV (-1.0 percentage unit). For IBS-D, alosetron and tricyclic anti-depressants caused constipation among a respective 16.9% and 13.0% resulting in a FNV of -3.6 and -0.5 percentage units. Among all therapies, only rifaximin did not cause the adverse event opposite the underlying motility complaint and the drug only had benefit, not detriment.

CONCLUSIONS:

Functional net value (FNV) offers a method of evaluating the net benefit of a drug in IBS. Most IBS treatments have a negative effect on IBS that exceeds the benefits.

• Authors: E Shah, M Pimentel
• Journal: Alimentary pharmacology & therapeutics (Aliment Pharmacol Ther) Vol. 39 Issue 9 Pg. 973-83 (May 2014) ISSN: 1365-2036 [Electronic] England
• PMID: 24612075 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
• Copyright: © 2014 John Wiley & Sons Ltd.

Chemical References

• Antidepressive Agents, Tricyclic
• Gastrointestinal Agents

Topics

• Antidepressive Agents, Tricyclic (adverse effects, therapeutic use)
• Constipation (drug therapy, etiology)
• Diarrhea (drug therapy, etiology)
• Gastrointestinal Agents (adverse effects, therapeutic use)
• Humans
• Irritable Bowel Syndrome (drug therapy, physiopathology)