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 diarrhea resulting from therapy for their constipation-predominant IBS (IBS-C) or constipation during treatment for diarrhea-predominant IBS (IBS-D), but still meet a unidirectional motility-based FDA endpoint.
Drs Shah and Pimentel from California, USA weighed the reported efficacy of existing therapies based on patient-reported outcomes with negative intestinal side effects in controlled clinical trial data.
The team analyzed 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.
|Linaclotide caused diarrhea in 15% resulting in negative FNV|
|Alimentary Pharmacology & Therapeutics|
The researchers found that for treating IBS-C, lubiprostone caused diarrhea in excess of placebo in 4% of patients, leading to a FNV of 3.9 percentage units.
The team noted that linaclotide caused diarrhea in 15% resulting in negative FNV.
For IBS-D, the team found that alosetron and tricyclic anti-depressants caused constipation among a respective 17% and 13% 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.
Dr Pimentel's team concludes, "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."