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| |  DG DISPATCH - DDW: COX-2 Inhibitors Show Good Pain Relief, Safety Record By Anne Scheck Special to DG News
SAN DIEGO, CA -- June 2, 2000 -- Studies on the COX-2 inhibitors show that their efficacy mirrors that of non-steroidal anti-inflammatory drugs (NSAIDs) in the treatment in osteoarthritis, rheumatoid arthritis and wound pain, according to Gary Williams, MD, who spoke at a symposia given here during Digestive Disease Week. Dr. Williams, head of the division of rheumatology at the Scripps Clinic and Research Foundation, in La Jolla, CA, reviewed recent studies on the these inhibitors, which have proven to be extremely selective pharmacologically. So far, COX-2 inhibitors have been used mainly as an alternative for management of pain and inflammation in patients who cannot tolerate long-term therapy with NSAIDs. The apparent reluctance to use agents such as celecoxib as first-line treatment probably stems from the fact they have not had the long medical track record of their NSAID counterparts, he said. However, that’s been changing, he stressed. Post-surgical studies now show that even small doses of celecoxib are effective in controlling wound pain post-operatively. Investigations involving patients with arthritis show significant and similar reductions in assessed pain with this COX-2 inhibitor. Moreover, phase III osteoarthritis trials with celecoxib showed significant reductions in assessed knee pain at 12 weeks with celecoxib, at either 100 mg or 200 mg bid, compared with naproxen at 500 mg bid. Pivotal Phase III trials of rheumatoid arthritis showed strikingly similar results. Patients on celecoxib reported significant reductions in the number of painful joints at 12 weeks, compared with the findings in the placebo group. The reductions were seen when celecoxib was taken at 100 mg or 200 mg bid compared with naproxen at 500 mg bid, he said. In studies comparing celecoxib and hydrocodone for relief of post-surgical pain, celecoxib exhibited a fast onset of action that was comparable to that of hydrocodone. In addition, there have been lower side effects for 24-hour relief. A single dose of Celecoxib 200 mg displayed analgesic activity in patients with moderate to severe post-orthopedic surgical pain. Celecoxib 200 mg q8h prn for five days demonstrated analgesic efficacy similar to a combination of hydrocodone 10 mg and acetaminophen 1000 mg. Celecoxib was safe and well-tolerated and was associated with a significantly lower incidence of adverse events than were associated with the combination of hydrocodone and acetaminophen, he said. Studies on the COX-2 inhibitor rofecoxib, another COX-2 inhibitor, demonstrated that its effectiveness mimics that of celecoxib, suggesting that it may add another agent to the armamentarium for arthritis. Several randomized investigations have tested the hypothesis that rofecoxib would cause fewer GI ulcers than ibuprofen. The data have shown rofecoxib 25 mg daily is effective in the treatment of osteoarthritis. It causes fewer gastroduodenal complications, such as ulcers, than an equally effective dose of ibuprofen -- 800 mg three times daily. Celecoxib does not seem to have any dose-dependent side effects, such as peripheral edema or hypertension. However, dose-dependent effects have been noted with rofecoxib, for unknown reasons, he said. Compared with currently available NSAIDs, the more-specific COX-2 inhibitors would be expected to cause less gastrointestinal toxicity. Prostaglandin production at inflammatory sites seems to occur via induction of COX-2; prostaglandin production in the normal gastrointestinal tract -- presumably critical for mucosal integrity -- is mediated by cyclooxygenase (COX)-1. It was suspected that the brain might be affected at high doses. However, neither of two theoretical side effects in brain function -- headache or confusion -- have been documented, Dr. Williams said. Kidney-related blood pressure changes have been seen with rofecoxib, for unknown reasons, but renal hypertension appears to be dose-related. At lower doses, such as 12.5 mg or 25 mg bid, no significant changes occur, he added. In fact, the toxicity has been so low and the safety profile so promising that there is speculation COX-2 inhibitors will all but replace NSAIDs. "I don't think we can make those predictions," Dr. Williams said. "At this point, I think it will be a function of the market place," he speculated. Related Link: celecoxib.
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