A randomized, double-blind, crossover clinical trial of diclofenac plus misoprostol versus acetaminophen in patients with osteoarthritis of the hip or knee

Objective. To perform a randomized, double-blind, crossover clinical trial of diclofenac + misoprostol versus acetaminophen in ambulatory patients wit h osteoarthritis of the hip or knee. Methods. Patients in 12 ambulatory care settings were eligible if they were age >40 years and if they had Kellgren/Lawrence radiographic grade 2-4 ost eoarthritis of the knee or hip and a score of greater than or equal to 30 m m on a 100-mm visual analog pain scale. Patients were randomized to one of two groups, 75 mg diclofenac + 200 mug misoprostol twice daily or 1,000 mg acetaminophen 4 times daily (each for 6 weeks), and were then crossed over to the other treatment for 6 weeks. A placebo was included in each treatmen t regimen to enable double blinding. The primary outcome measures were the Western Ontario and McMaster Universities Osteoarthritis Index and the visu al analog pain scale of the Multidimensional Health Assessment Questionnair e. Safety was assessed using a standard form to review adverse events. Results. We enrolled 227 patients, of whom 218 provided data for the first treatment period and 181 provided data for both treatment periods. Signific antly higher levels of improvement in the primary outcomes were seen for di clofenac + misoprostol than for acetaminophen (P < 0.001). Adverse events w ere more common when patients took diclofenac + misoprostol (P = 0.046). Di clofenac + misoprostol was rated as "better" or "much better" by 57% of the 174 patients who provided such ratings for both treatment periods, while a cetaminophen was rated as "better" or "much better" by 20% of these patient s, and 22% reported no difference (P < 0.001). Differences favoring diclofe nac + misoprostol over acetaminophen were greater in patients with more sev ere osteoarthritis according to baseline pain scores, radiographs, or numbe r of involved joints. Conclusion. Patients with osteoarthritis of the hip or knee had significant ly greater improvements in pain scores over 6 weeks with diclofenac + misop rostol than with acetaminophen, although patients with mild osteoarthritis had similar improvements with both drugs. Acetaminophen was associated with fewer adverse events.