DICLOFENAC MISOPROSTOL COMPARED WITH DICLOFENAC IN THE TREATMENT OF OSTEOARTHRITIS OF THE KNEE OR HIP - A RANDOMIZED, PLACEBO-CONTROLLED TRIAL/

Objective, Gastric (GU) and duodenal ulcers (DU) are common adverse ef fects of nonsteroidal antiinflammatory drugs (NSAID). Endoscopically d iagnosed upper gastrointestinal (GI) ulceration occurs in about 24% of longterm NSAID users. Coadministration of misoprostol with the NSAID reduces the incidence of NSAID induced GU and DU and their complicatio ns. However, compliance is limited by the different dosing regimens of misoprostol and NSAID and GI symptoms associated with misoprostol at its recommended qid dose. We compared the efficacy, safety, and incide nce of endoscopic upper GI ulceration associated with the administrati on of 2 combinations of diclofenac (50 or 75 mg) and misoprostol 200 m u g (D50/M200 tid, D75/M200 bid), diclofenac 75 mg bid, and placebo in a 6 week, randomized, double blind study in patients with osteoarthri tis (OA) of the knee or hip. Methods. A total of 572 patients with sym ptomatic OA of the knee or hip and history of GU, DU, or 10 or more er osions were randomized to receive D50/M200 tid, D75/M200 bid, diclofen ac 75 mg bid, or placebo for 6 weeks. Arthritis assessments were perfo rmed at baseline, 2, and 6 weeks, and upper GI endoscopies at baseline and end of treatment. Results. All active treatment groups were signi ficantly better than placebo, at all visits, in improving OA symptoms. There were no significant differences in arthritis efficacy between t he diclofenac/misoprostol combinations and diclofenac. However, endosc opically diagnosed GU and/or DU were significantly less frequent in pa tients receiving D50/M200 rid (8%), D75/M200 bid (7%), and placebo (4% ) compared to diclofenac 75 mg bid (17%), Adverse events were not diff erent between the active treatment groups, except for higher incidence s of flatulence with D75/M200 and diarrhea with D50/M200. Conclusion. Diclofenac 50 mg/misoprostol 200 mu g tid and diclofenac 75 mg/misopro stol 200 mu g bid are as efficacious as diclofenac 75 mg bid in the tr eatment of OA, but are associated with a significantly lower incidence of gastric and/or duodenal ulcers.