Pharmacological therapy of osteoarthritis

In 2000, both the American College of Rheumatology (ACR) and the European L eague of Associations of Rheumatology (EULAR) published recommendations for the use of pharmacological therapy in the treatment of patients with lower limb osteoarthritis. These recommendations are based on the level of evide nce observed in systematic reviews and/or meta-analyses of published random ized controlled trials as well as expert opinion. Acetaminophen (paracetamo l) is considered as first-line oral therapy for symptomatic lower limb oste oarthritis with mild to moderate pain because it is more efficacious than p lacebo and is generally considered to be safe and well tolerated. Data obta ined in recent trials and the results of a meta-analysis, however, show tha t acetaminophen is not as efficacious as non-steroidal anti-inflammatory dr ugs (NSAIDs) for pain at rest and pain on motion. Furthermore, data from a recent epidemiological study suggest that use of high-dose acetaminophen (> 2 g/day) may convey the same magnitude of increased risk for serious upper gastrointestinal adverse events as NSAIDs. NSAIDs have demonstrated efficacy superior to placebo in patients with oste oarthritis. The newer cyclo-oxygenase (COX)-2-specific inhibitors (coxibs) have comparable efficacy to traditional dual inhibitor NSAIDs and have demo nstrated a better gastrointestinal safety profile. Thus, for patients who h ave severe pain and/or signs of inflammation or who have failed to respond to acetaminophen, the use of a coxib should be considered, especially if th e patient is at increased risk for serious upper gastrointestinal adverse e vents from a traditional NSAID. Compounds different from pure analgesics and NSAIDs are also used for the m anagement of patients with osteoarthritis. Recent clinical trials have demo nstrated statistically significant efficacy of such compounds (e.g. chondro itin sulphate, diacerhein, glucosamine sulphate) with the following charact eristics: (1) the effect size seems to be of slightly lower magnitude than that seen for NSAIDs; (2) the onset of action is delayed for approximately 4 to 6 weeks; and (3) the symptomatic effect is maintained after stopping t he treatment for periods of 4 to 8 weeks. The methodology for evaluating the possible structure-modifying effect of d rugs has dramatically improved during the past decade. Two agents have demo nstrated a beneficial structural effect: glucosamine sulphate in osteoarthr itis of the knee, and diacerhein in osteoarthritis of the hip. The clinical relevance of such an effect needs to be further evaluated in long-term out come studies.