Effects of baseline abdominal pain and bloating on response to lubiprostone in patients with irritable bowel syndrome with constipation

Abstract

SummaryBackgroundLubiprostone (8 μg b.d.) received US Food and Drug Administration (FDA) approval in 2008 for the treatment of constipation‐predominant irritable bowel syndrome (IBS‐C) in women aged ≥18 years. In 2012, the FDA issued new guidance for IBS‐C clinical trials, recommending a composite endpoint incorporating both abdominal pain and stool frequency.AimIn a post hoc analysis, similar criteria were applied to data from two pivotal, phase 3, double‐blind, randomised trials of lubiprostone in patients with IBS‐C.MethodsIncluded patients had a baseline spontaneous bowel movement (SBM) frequency <3/week and abdominal pain or bloating ratings ≥1.36 on a 5‐point scale [0 (absent) to 4 (very severe)]. Responders (composite endpoint) had a mean pain reduction ≥30% compared with baseline, and an increase from baseline of ≥1 SBM/week for ≥6 of the 12 treatment weeks. Lubiprostone effects on abdominal pain alone were also evaluated, as were bloating alone and in a composite endpoint with stool frequency.ResultsIn pooled data, 325 patients received lubiprostone and 180 received placebo. Rates of response were higher with lubiprostone vs. placebo for the composite endpoint of improved pain and stool frequency (26.3% vs. 15.3%, respectively; P = 0.008) and the composite endpoint of improved bloating and stool frequency (23.8% vs. 12.6%, respectively; P = 0.012). Response rates were also higher with lubiprostone vs. placebo for abdominal pain alone (P = 0.005) and bloating alone (P = 0.012).ConclusionLubiprostone was significantly more effective than placebo in improving abdominal pain or bloating, and also in composite endpoints that included stool frequency.

Randomised clinical trial: pregabalin vs placebo for irritable bowel syndrome

“…A systematic review of IBS treatments also suggests that linaclotide has beneficial effects on IBS pain . Lubiprostone decreases pain, bloating and improves bowel habit in those with IBS with constipation . Eluxadoline was more effective than placebo in reduction of abdominal pain and improvement in stool consistency .…”

Chronic stress and intestinal permeability: Lubiprostone regulates glucocorticoid receptor‐mediated changes in colon epithelial tight junction proteins, barrier function, and visceral pain in the rodent and human

“…The signal transduction pathway includes activation of CIC‐2 channels resulting in a chloride‐rich fluid secretion, activation of prostaglandin E type receptors with increase in mucus/fluid secretion, and restitution of epithelial cell barrier properties . The current study demonstrates that lubiprostone significantly reduced chronic stress‐induced visceral hyperalgesia in the rat, which is consistent with the effects reported in IBS patients . This beneficial effect of lubiprostone most likely contributes to the prevention of chronic stress‐induced changes in epithelial tight junction proteins including claudin‐1, claudin‐2, and occludin, and subsequent recovery of paracellular permeability in both in vivo and in vitro models.…”

“…It has been reported that lubiprostone significantly improves symptoms in patients with chronic constipation 51 and is more effective than placebo in improving abdominal pain or bloating in IBS patients with constipation. 52 The signal transduction pathway includes activation of CIC-2 channels resulting in a chloride-rich fluid secretion, activation of prostaglandin E type receptors with increase in mucus/fluid secretion, and restitution of epithelial cell barrier properties. 26,28,51 The current study demonstrates that lubiprostone significantly reduced chronic stress-induced visceral hyperalgesia in the rat, which is consistent with the effects reported in IBS patients.…”

“…26,28,51 The current study demonstrates that lubiprostone significantly reduced chronic stress-induced visceral hyperalgesia in the rat, which is consistent with the effects reported in IBS patients. 52 On the other hand, heat-shock proteins have been reported to regulate chloride channel expression and function. 53 Recovery of p23 and FKBP5 by lubiprostone may, therefore, lead to enhancement of chloride channel activity and fluid secretion to reduce chronic stress-induced symptoms.…”

Painful and Painless Constipation: All Roads Lead to (A Change in) Rome

“…This threshold score of 4 or greater on a scale of 1-10 is similar to the US Food and Drug Administration (FDA) recommended eligibility criteria in IBS-C, i.e., a weekly average of worst daily abdominal pain score of ≥ 3.0 on a 0-10 scale [9]. The baseline pain severity score, which was evaluated on a 5-point scale (0-4), predicted the response to lubiprostone in IBS-C [10]. A baseline pain score of ≥ 3 on an 11-point scale (0-10) corresponds to a score ≥ 1.36 on a 5-point scale [9].…”