Less Small-Bowel Injury With Lumiracoxib Compared With Naproxen Plus Omeprazole

• Published in: Clinical gastroenterology and hepatology Vol. 6; no. 5; pp. 536 - 544
• Main Authors: Hawkey, Christopher J, Ell, Christian, Simon, Bernd, Albert, Jörg, Keuchel, Martin, McAlindon, Mark, Fortun, Paul, Schumann, Stefan, Bolten, Wolfgang, Shonde, Anthony, Hugot, Jean–Louis, Yu, Vincent, Arulmani, Udayasankar, Krammer, Gerhard, Rebuli, Rosemary, Toth, Ervin
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-05-2008
• Subjects: Administration, Oral; Adult; Aged; Capsule Endoscopes; Clinical Medicine; Cross-Over Studies; Cyclooxygenase Inhibitors - administration & dosage; Cyclooxygenase Inhibitors - adverse effects; Diclofenac - administration & dosage; Diclofenac - adverse effects; Diclofenac - analogs & derivatives; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Endoscopy, Gastrointestinal - methods; Female; Gastroenterologi; Gastroenterology and Hepatology; Humans; Intestinal Mucosa - drug effects; Intestinal Mucosa - pathology; Intestine, Small - drug effects; Intestine, Small - pathology; Klinisk medicin; Male; Medical and Health Sciences; Medicin och hälsovetenskap; Middle Aged; Naproxen - administration & dosage; Naproxen - adverse effects; Omeprazole - administration & dosage; Omeprazole - adverse effects; Probability; Reference Values; Risk Assessment; Ulcer - chemically induced; Ulcer - pathology; video capsule endoscopy; GI; OR; AE; CI; NSAID; adverse event; cyclooxygenase; odds ratio; COX; gastrointestinal; VCE; confidence interval; nonsteroidal anti-inflammatory drug
• ISSN: 1542-3565; 1542-7714; 1542-7714
• DOI: 10.1016/j.cgh.2007.12.023

Background & Aims: 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.