Etoricoxib results in fewer upper GI events compared with diclofenac users according to MEDAL program

Key Points

Patients with osteoarthritis or rheumatoid arthritis who are taking etoricoxib may experience significantly fewer upper gastrointestinal (GI) events compared with those taking diclofenac, according to the pooled results of 3 randomized trials.

The results are derived from a safety analysis of the Multinational Etoricoxib and Diclofenac Arthritis Long-Term (MEDAL) program, conducted at 1,380 sites in 46 countries. The MEDAL program included data from 3 double-blind randomized comparisons of etoricoxib 60 or 90 mg/d and diclofenac 150 mg/d in 34,701 patients aged ≥50 years with osteoarthritis (n=24,913) or rheumatoid arthritis (n=9,787). The trials included the MEDAL study, the Etoricoxib vs Diclofenac Sodium Gastrointestinal Tolerability and Effectiveness (EDGE) study, and the EDGE II study.

The MEDAL program's primary end points were thrombotic cardiovascular events and GI clinical events (ie, bleeding, perforation, ulcer); patients were also assessed for complicated events (ie, perforation, obstruction, significant bleeding). The same outcomes were measured in patients taking concomitant proton pump inhibitors (PPIs) or low-dose aspirin (100 mg/d). At baseline, ≥1 GI risk factor was detected in 66% of patients (n=11,565) in the etoricoxib group and in 67% (n=11,500) of patients in the diclofenac group. Follow-up visits were conducted every 4 months; scheduled telephone calls occurred between visits.

A total of 13,862 (40%) patients used PPIs concomitantly for >75% of the study duration; 11,418 patients (33%) used low-dose aspirin concurrently. There was no significant difference in treatment effects for these patients. Cardiovascular risk factors were more likely in patients taking aspirin than in nonusers. GI risk factors were more common with frequent PPI use compared with non-PPI users.

The most common GI events were uncomplicated ulcers (n=253) and complicated or uncomplicated upper GI bleeding (n=154); gastric ulcers were nearly twice as frequently the cause of bleeding compared with duodenal ulcers.

Discontinuation of treatment due to dyspepsia was less likely with etoricoxib use (n=327) compared with diclofenac use (n=424; HR=0.75; 95% CI, 0.65–0.87).

SOURCE Laine L, Curtis SP, Cryer B, Kaur A, Cannon CP; for the MEDAL Steering Committee. Assessment of upper gastrointestinal safety of etoricoxib and diclofenac in patients with osteoarthritis and rheumatoid arthritis in the Multinational Etoricoxib and Diclofenac Arthritis Long-term (MEDAL) programme: a randomised comparison. Lancet. 2007; 369:465–472.