Conflicting evidence about the gastrointestinal (GI) benefits of using cyclo-oxygenase-2 (COX-2) specific inhibitors over non-selective non-steroidal anti-inflammatory drugs (NSAIDs) has been reported this week.
Dr Michael Jones (Veterans Affairs medical centre, California, US) and colleagues have questioned the ability of COX-2 specific inhibitors to prevent GI adverse effects (Nature Medicine 1999;5:1418). Angiogenesis (formation of new blood vessels) is required for wound and ulcer healing and the authors say that the growth of new blood vessels is regulated by both COX-1 and COX-2.
In three experimental models, COX-2 selective drugs were observed to inhibit angiogenesis which is required for ulcer healing. They comment that a selective COX-2 inhibitor (L-745,337) has been demonstrated to delay the healing of gastric ulcers, partly through the inhibition of angiogenesis, which added weight to their findings. Their results "challenge the premise that selective COX-2 inhibitors will not affect the gastrointestinal tract and ulcer/wound healing".
However, angiogenesis is also essential for the growth and metastasis of solid tumours. The findings, therefore, indicate that compounds which suppress angiogenesis, like COX-2 specific inhibitors, have a potential therapeutic role as anti-cancer drugs by preventing tumour formation, the researchers say.
Further evidence to support the GI benefits of COX-2 inhibitors came from two sources. In a study presented at the American College of Rheumatology's annual scientific meeting on November 17, Watson et al (Merck & Co) concluded that patients treated with rofecoxib required less GI co-medication and fewer GI procedures than those treated with non-specific NSAIDs. The 12 month study compared 3,357 patients taking rofecoxib and 1,564 taking NSAIDs (ibuprofen, diclofenac or nabumetone) and recorded the use of GI co-medication including antacids, antispasmodics, H2 antagonists and proton pump inhibitors.
The GI safety of celecoxib was supported by a study conducted by Dr Lee Simon (Harvard medical school, US) and colleagues. The efficacy and GI effects of celecoxib and naproxen were compared in 1,149 patients with rheumatoid arthritis. A less frequent incidence of endoscopic ulcers was observed in the patients receiving celecoxib compared with naproxen, they concluded (Journal of the American Medical Association 1999;282:1921).