Use of gastroprotective agents and discontinuations due to dyspepsia with the selective cyclooxygenase-2 inhibitor etoricoxib compared with non-selective NSAIDs.
BACKGROUND
Most nonsteroidal anti-inflammatory drugs (NSAIDs) are non-selective cyclooxygenase-1 (COX-1) and COX-2 inhibitors and are associated with upper gastrointestinal (GI) dyspeptic symptoms often resulting in GI co-medication usage or treatment discontinuation.


OBJECTIVE
To compare the rates of new use of gastroprotective agents and discontinuations due to dyspepsia with the COX-2 selective inhibitor etoricoxib compared with non-selective NSAIDs.


METHODS
This pre-specified combined analysis used data from nine randomized, double-blind, controlled, clinical trials with etoricoxib in patients with osteoarthritis, rheumatoid arthritis, chronic low back pain, or ankylosing spondylitis. The cumulative incidences of (1) new use (new prescription or increased dose) of gastroprotective agents (GPA) and (2) discontinuation due to dyspeptic symptoms were compared among patients treated with etoricoxib (60 mg, 90 mg, or 120 mg daily) vs. non-selective NSAIDs (diclofenac 50 mg. t.i.d. or naproxen 500 mg. b.i.d.).


RESULTS
The overall rates/100 patient-years for new use of GPAs were 9.1 and 13.0 for etoricoxib and NSAIDs, respectively (RR = 0.75; 95% confidence interval [CI] 0.64, 0.89; p < 0.001). A benefit with etoricoxib was seen in the first 6 months when most new GPA usage occurred; after 6 months new use of GPAs was similar between etoricoxib and NSAIDs. The rates/100 patient-years of treatment discontinuation due to dyspeptic symptoms with etoricoxib and NSAIDs were 1.5 and 2.7, respectively (RR = 0.60; 95% CI 0.41, 0.87; p = 0.007). Analyses of placebo-controlled treatment periods showed significantly more new GPA use and more discontinuations due to dyspeptic symptoms with NSAIDs vs. placebo, but not with etoricoxib vs. placebo.


CONCLUSIONS
In this combined analysis of clinical trials of patients with OA, RA, chronic low back pain, or AS, new use of gastroprotective agents was significantly lower with etoricoxib than with the comparator non-selective NSAIDs during the initial 6 months of treatment and similar thereafter. There were significantly fewer discontinuations for dyspeptic symptoms with etoricoxib than with NSAIDs over the entire follow-up period.
Watson
D J
DJ
Merck Research Laboratories, West Point, PA 19486, USA. douglas_watson@merck.com
Bolognese
J A
JA
Yu
C
C
Krupa
D
D
Curtis
S
S
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects* / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy; D016861:Cyclooxygenase Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D004311:Double-Blind Method; D004415:Dyspepsia / Q000139:chemically induced*; D000077613:Etoricoxib; D006801:Humans; D017116:Low Back Pain / Q000188:drug therapy; D010003:Osteoarthritis / Q000188:drug therapy; D010349:Patient Compliance; D020011:Protective Agents / Q000627:therapeutic use*; D011725:Pyridines / Q000009:adverse effects* / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D012189:Retrospective Studies; D013167:Spondylitis, Ankylosing / Q000188:drug therapy; D013450:Sulfones / Q000009:adverse effects* / Q000627:therapeutic use
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D020011:Protective Agents; D011725:Pyridines; D013450:Sulfones; D000077613:Etoricoxib