title: Comparison of gastroduodenal ulcer incidence in healthy Japanese subjects taking celecoxib or loxoprofen evaluated by endoscopy: a placebo-controlled, double-blind 2-week study.
abstract: BACKGROUND
  Although nonsteroidal anti-inflammatory drugs (NSAIDs) are widely prescribed globally, their chronic use increases the risk of upper gastrointestinal (GI) damage. Cyclooxygenase-2-selective NSAIDs are considered to reduce this risk. Current guidelines in Japan recommend loxoprofen sodium (loxoprofen), a pro-drug in the propionic acid class of nonselective NSAIDs, as first-line therapy in rheumatoid arthritis.
  
  
  OBJECTIVE
  To confirm the superiority of celecoxib, a cyclooxygenase-2-selective NSAID, to loxoprofen in the incidence of gastroduodenal (GD) endoscopic ulcers.
  
  
  METHODS
  A randomised, multicentre, placebo-controlled, double-blind, phase IV clinical trial in healthy Japanese volunteers [mean age 57.5 (range: 40-74) years; >70% female], stratified by Helicobacter pylori status at screening (~40% positive) and randomised 2:2:1 to receive celecoxib 100 mg b.d., loxoprofen 60 mg t.d.s. or placebo. Primary end point was incidence of any GD endoscopic ulcers after 2 weeks of treatment.
  
  
  RESULTS
  Of 190 randomised subjects, 189 received at least one dose of celecoxib (n = 76), loxoprofen (n = 76), or placebo (n = 37). Incidence of GD ulcers was 1.4%, 27.6% and 2.7% in the celecoxib, loxoprofen and placebo groups respectively (P < 0.0001 in favour of the celecoxib group); incidence of adverse events (AEs) was 34.2%, 51.3% and 21.6% in the celecoxib, loxoprofen and placebo groups respectively. No serious or severe AEs were reported.
  
  
  CONCLUSIONS
  Celecoxib 100 mg b.d. was superior to loxoprofen 60 mg t.d.s. regarding the incidence of gastro-duodenal endoscopic ulcers over 2 weeks. Celecoxib was well tolerated and no major safety concerns were observed.
authors.affiliation: Department of Gastroenterology, Nippon Medical School, Graduate School of Medicine, Tokyo, Japan. choitsu@nms.ac.jp
authors.forename: C
authors.initials: C
authors.lastname: Sakamoto
authors.forename: T
authors.initials: T
authors.lastname: Kawai
authors.forename: S
authors.initials: S
authors.lastname: Nakamura
authors.forename: T
authors.initials: T
authors.lastname: Sugioka
authors.forename: J
authors.initials: J
authors.lastname: Tabira
mesh_terms: D000328:Adult; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D000068579:Celecoxib; D052246:Cyclooxygenase 2 Inhibitors / Q000627:therapeutic use*; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use*; D004311:Double-Blind Method; D016099:Endoscopy, Gastrointestinal; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D010437:Peptic Ulcer / Q000188:drug therapy* / Q000453:epidemiology; D010666:Phenylpropionates / Q000627:therapeutic use*; D011720:Pyrazoles / Q000627:therapeutic use*; D013449:Sulfonamides / Q000627:therapeutic use*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D010666:Phenylpropionates; D011720:Pyrazoles; D013449:Sulfonamides; C040656:loxoprofen; D000068579:Celecoxib