Clinical Question: Are patients taking rofecoxib less likely than patients taking high-dose naproxen to discontinue treatment because of gastrointestinal (GI) side effects?

Setting: Outpatient (primary care)

Study Design: Randomized controlled trial (double-blinded)

Synopsis: In this study, 5,557 patients were enrolled from 500 sites (mostly primary care) in the United States and Sweden. Participants were 63 years of age, on average, and had arthritis of the knee, hip, hand, or spine for at least six months that required analgesic treatment. They were randomized to receive rofecoxib in a dosage of 25 mg daily or naproxen in a dosage of 500 mg twice daily. Allocation to treatment groups may not have been concealed from the enrolling investigators. Patients took both drugs (with the corresponding placebo) for three months. They were allowed to continue low-dose aspirin during the study (13 percent of the patients) and could use acetaminophen for additional pain relief and acid-reduction therapy for GI symptoms.

Investigators used the low, analgesic dosage of rofecoxib and the high, anti-inflammatory dosage of naproxen. The study would have been much more useful had they used one half the dosage of naproxen.

By the end of three months, significantly more patients in the naproxen group had discontinued treatment because of GI side effects (8.1 versus 5.9 percent in the rofecoxib group; P = .005). In other words, one additional patient would drop out of treatment for every 46 patients treated with naproxen instead of rofecoxib (number needed to harm = 46; 95 percent confidence interval, 31 to 167). In terms of cost, each patient would pay an additional $192 over the course of three months for this decreased risk. In more general terms, an additional $6,000 to $32,000 would be spent on rofecoxib rather than naproxen to prevent one patient from discontinuing therapy because of side effects. It might be easier just to use a lower dosage of naproxen.

Bottom Line: Patients with osteoarthritis who are taking low-dose rofecoxib (25 mg daily) are less likely to discontinue treatment because of side effects than patients taking high-dose naproxen (1,000 mg daily). It is not known whether low-dose rofecoxib produces the same results as a lower dosage of naproxen. (Level of Evidence: 1b)