Less small-bowel injury with lumiracoxib compared with naproxen plus omeprazole.
OBJECTIVE
The selective cyclooxygenase-2 inhibitor lumiracoxib has been shown to reduce endoscopically detected ulcers and ulcer complications in the upper gastrointestinal tract compared with nonselective nonsteroidal anti-inflammatory drugs. We investigated whether lumiracoxib would reduce small-bowel injury compared with naproxen plus omeprazole.


METHODS
Healthy volunteers were randomized to receive lumiracoxib 100 mg once daily, naproxen 500 mg twice daily plus omeprazole 20 mg once daily, or placebo in a 16-day double-blind, parallel-group study. Small-bowel mucosal injury and inflammation were assessed by video capsule endoscopy, the lactulose:L-rhamnose permeability assessment, and the fecal calprotectin test.


RESULTS
Of 152 randomized subjects, 139 completed the study with valid video capsule endoscopies (lumiracoxib, n = 47; naproxen plus omeprazole, n = 45; placebo, n = 47). Compared with placebo, an increased number of subjects on naproxen plus omeprazole had small-bowel mucosal breaks (77.8% vs 40.4%, P < .001), with increased permeability (P = .023) and increased fecal calprotectin (increase, 96.8 vs 14.5 mg/kg for placebo; P < .001). With lumiracoxib, 27.7% of subjects had small-bowel mucosal breaks (P = .196 vs placebo; P < .001 vs naproxen), there was no increase in permeability (P = .157 vs placebo; P = .364 vs naproxen), and no increase in fecal calprotectin (-5.7 mg/kg; P = .377 vs placebo; P < .001 vs naproxen).


CONCLUSIONS
As assessed by 3 different measures, acute small-bowel injury on lumiracoxib treatment is less frequent than with naproxen plus omeprazole and similar to placebo.
Hawkey
Christopher J
CJ
Wolfson Digestive Diseases Centre, University Hospital, Nottingham, United Kingdom. cj.hawkey@nottingham.ac.uk
Ell
Christian
C
Simon
Bernd
B
Albert
Jörg
J
Keuchel
Martin
M
McAlindon
Mark
M
Fortun
Paul
P
Schumann
Stefan
S
Bolten
Wolfgang
W
Shonde
Anthony
A
Hugot
Jean-Louis
JL
Yu
Vincent
V
Arulmani
Udayasankar
U
Krammer
Gerhard
G
Rebuli
Rosemary
R
Toth
Ervin
E
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D053705:Capsule Endoscopes; D018592:Cross-Over Studies; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D004008:Diclofenac / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D016099:Endoscopy, Gastrointestinal / Q000379:methods; D005260:Female; D006801:Humans; D007413:Intestinal Mucosa / Q000187:drug effects / Q000473:pathology; D007421:Intestine, Small / Q000187:drug effects* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009288:Naproxen / Q000008:administration & dosage / Q000009:adverse effects*; D009853:Omeprazole / Q000008:administration & dosage / Q000009:adverse effects*; D011336:Probability; D012016:Reference Values; D018570:Risk Assessment; D014456:Ulcer / Q000139:chemically induced* / Q000473:pathology
D016861:Cyclooxygenase Inhibitors; D004008:Diclofenac; D009288:Naproxen; D009853:Omeprazole; C473384:lumiracoxib