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



In 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.



Included 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.



In 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).



Lubiprostone was significantly more effective than placebo in improving abdominal pain or bloating, and also in composite endpoints that included stool frequency.
David Geffen School of Medicine at UCLA, Los Angeles, CA, USA. linchang@mednet.ucla.edu.
L
L
Chang
University of Michigan, School of Medicine, Ann Arbor, MI, USA.
W D
WD
Chey
University of North Carolina and Drossman Gastroenterology, Chapel Hill, NC, USA.
D
D
Drossman
Sucampo Pharma Americas, LLC, Bethesda, MD, USA.
T
T
Losch-Beridon
Sucampo Pharma Americas, LLC, Bethesda, MD, USA.
M
M
Wang
Sucampo AG, Zug, Switzerland.
P
P
Lichtlen
Sucampo Pharma Americas, LLC, Bethesda, MD, USA.
S
S
Mareya
D015746:Abdominal Pain / Q000188:drug therapy*; D000328:Adult; D003248:Constipation / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D005414:Flatulence / Q000188:drug therapy*; D006801:Humans; D043183:Irritable Bowel Syndrome / Q000188:drug therapy*; D000068238:Lubiprostone / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged
D000068238:Lubiprostone
J Neurogastroenterol Motil. 2016 Jan 31;22(1):31-45
26717930
World J Gastroenterol. 2014 Jul 21;20(27):8898-909
25083062
Am J Gastroenterol. 2010 Apr;105(4):731-5
20372121
Aliment Pharmacol Ther. 2012 Mar;35(5):587-99
22251419
Clin Gastroenterol Hepatol. 2012 Jul;10(7):712-721.e4
22426087
Neurogastroenterol Motil. 2014 Mar;26(3):326-33
24382134
Aliment Pharmacol Ther. 2009 Feb 1;29(3):329-41
19006537
Aliment Pharmacol Ther. 2008 Apr;27(8):685-96
18248656
Gastroenterology. 2006 Apr;130(5):1480-91
16678561
Am J Gastroenterol. 2012 Nov;107(11):1702-12
22986437