Improvements with esomeprazole in patients with upper gastrointestinal symptoms taking non-steroidal antiinflammatory drugs, including selective COX-2 inhibitors.
OBJECTIVE
Upper gastrointestinal (GI) symptoms are common in patients using non-steroidal antiinflammatory drugs (NSAIDs) including selective cyclooxygenase (COX)-2 inhibitors and may be acid related. We therefore assessed esomeprazole treatment for upper GI symptoms in these patients.


METHODS
A total of 794 and 848 continuous NSAID users, free of gastroduodenal ulcers, erosive esophagitis, and Helicobacter pylori, were enrolled into two identical, multinational, multicenter double-blind studies (NASA1, SPACE1). Moreover, 608 and 556 patients were randomized to receive 4 wk esomeprazole 20 mg, or 40 mg, or placebo once daily. The primary variable was the patient-reported change in the upper GI symptom (pain, discomfort, or burning in the upper abdomen) score on a 7-graded severity scale (0-6) from the 7 days prior to treatment to the last 7 days in the study.


RESULTS
Esomeprazole was associated with highly significant symptom improvement compared to placebo. Symptom improvements were 2.30 mean [SD 1.63] on esomeprazole 20 mg and 2.03 [1.56] on esomeprazole 40 mg versus 1.64 [1.57] on placebo in NASA1 and 2.17 [1.34] and 2.12 [1.48]versus 1.56 [1.26], respectively, in SPACE1 (all placebo comparisons at least p < 0.001). Esomeprazole-improved symptoms in patients taking selective COX-2 inhibitors, with changes of 2.21 [1.46] and 1.92 [1.38]versus 1.64 [1.46] in NASA1 and 2.20 [1.26] and 2.24 [1.62]versus 1.58 [1.37] in SPACE1 (all placebo comparisons at least p < 0.05), as well as those on non-selective NSAIDs. Esomeprazole was well tolerated and associated with significant improvements in HRQL.


CONCLUSIONS
Esomeprazole 20 mg and 40 mg improve upper GI symptoms associated with continuous, daily NSAID therapy, including selective COX-2 inhibitors.
Hawkey
Chris
C
Institute of Clinical Research Trials Unit, University Hospital, Nottingham, UK.
Talley
Nicholas J
NJ
Yeomans
Neville D
ND
Jones
Roger
R
Sung
Joseph J Y
JJ
Långström
Göran
G
Naesdal
Jørgen
J
Scheiman
James M
JM
D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D000897:Anti-Ulcer Agents / Q000627:therapeutic use*; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000009:adverse effects*; D004311:Double-Blind Method; D064098:Esomeprazole / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D005764:Gastroesophageal Reflux / Q000517:prevention & control; D006356:Heartburn / Q000517:prevention & control; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors*; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D009325:Nausea / Q000517:prevention & control; D010146:Pain / Q000517:prevention & control; D010544:Peroxidases / Q000037:antagonists & inhibitors*; D010919:Placebos; D011451:Prostaglandin-Endoperoxide Synthases / Q000009:adverse effects*; D011788:Quality of Life; D016896:Treatment Outcome; D041742:Upper Gastrointestinal Tract / Q000187:drug effects*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000897:Anti-Ulcer Agents; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; D010919:Placebos; D010544:Peroxidases; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D064098:Esomeprazole