Currently 2 difference classes of
cyclooxygenase (COX)-2 inhibitors,
coxibs and relatively selective
COX-2 inhibitors, are available for patients requiring nonsteroidal anti-inflammatory drug (
NSAID)
therapy; their gastroprotective effect is hardly directly compared. The aim of this study was to compare the gastroprotective effect of relatively selective
COX-2 inhibitors with
coxibs. MEDLINE, EMBASE, and the Cochrane Library (from their inception to March 2015) were searched for potential eligible studies. We included randomized controlled trials comparing
coxibs (
celecoxib,
etoricoxib,
parecoxib, and
lumiracoxib), relatively selective
COX-2 inhibitors (
nabumetone,
meloxicam, and
etodolac), and nonselective
NSAIDs with a study duration ≥ 4 weeks. Comparative effectiveness and safety data were pooled by Bayesian network meta-analysis. The primary outcomes were
ulcer complications and symptomatic
ulcer. Summary effect-size was calculated as risk ratio (RR), together with the 95% confidence interval (CI). This study included 36 trials with a total of 112,351 participants. Network meta-analyses indicated no significant difference between relatively selective
COX-2 inhibitors and
coxibs regarding
ulcer complications (RR, 1.38; 95% CI, 0.47-3.27), symptomatic
ulcer (RR, 1.02; 95% CI, 0.09-3.92), and endoscopic
ulcer (RR, 1.18; 95% CI, 0.37-2.96). Network meta-analyses adjusting potential influential factors (age, sex, previous
ulcer disease, and follow-up time), and sensitivity analyses did not reveal any major change to the main results. Network meta-analyses suggested that relatively selective
COX-2 inhibitors and
coxibs were associated with comparable incidences of total adverse events (AEs) (RR, 1.09; 95% CI, 0.93-1.31), gastrointestinal AEs (RR, 1.04; 95% CI, 0.87-1.25), total withdrawals (RR, 1.00; 95% CI, 0.74-1.33), and gastrointestinal AE-related withdrawals (RR, 1.02; 95% CI, 0.57-1.74). Relatively selective
COX-2 inhibitors appear to be associated with similar gastroprotective effect and tolerability as
coxibs. Owing to the indirectness of the comparisons, future research is required to confirm the study conclusion.