Patient Population:

Adults with symptomatic OA of the knee. Mean age of participants was reported to be 62 years.

Intervention:

Naproxen-esomeprazole in a fixed dose combination. Dosage: 500mg/20mg twice daily.

Comparison:

The authors discuss 2 RCTs undertaken as non-inferiority trials, comparing the efficacy of the naproxen-esomeprazole combinations with active comparisons (COX-2 inhibitors or other oral analgesic therapies).

Outcome:

1. Treatment Efficacy:  Combination therapy was demonstrated to be non-inferior to celecoxib as assessed via WOMAC pain and function sub-scales. In one of the two trials, both active conditions, were superior to placebo, while in the other, only combination therapy demonstrated greater efficacy.
2. Safety: 7% of patients withdrew due to treatment-related adverse events. Pre-defined, GI-related adverse events were reported in approximate participants receiving combination therapy in one of the non-inferiority trials and 18.9% in the other (vs. 19.4% and 20.5% in the placebo conditions, respectively). The most commonly reported GI-related adverse events in the combination therapy groups were dyspepsia, nausea and upper abdominal pain. The upper GI tolerability profile appeared to be generally similar to celecoxib (200mg once daily).
3. Prevention of gastric ulcers:  Two trials were identified that compared treatment with combination therapy with enteric coated naproxen (500 mg/bid). Study endpoints were the incidence of endoscopically assessed ulcers at 1, 3 and 6 months. In both studies, use of combination therapy was associated with a significant reduction of risk for gastric ulcers overall (post hoc analysis): RRR=82.3% and 70.8%. Reduction in risk was observed from one month onward in both studies. Over 6 months, treatment related adverse events occurred in 78%/76.2% of patients assigned to combination therapy vs. 81.5%/82.9% of individuals assigned to enteric coated naproxen. The most commonly reported adverse events were erosive gastritis, gastritis and dyspepsia.