Results of an international multi-centre study in this week’s issue of THE LANCET suggest that the COX2 inhibitor lumiracoxib could be an effective treatment for osteoarthritis—its use was associated with an 80% reduction in gastric complications compared with other conventional anti-inflammatory drugs.
The use of non-selective non-steroidal anti-inflammatory drugs (NSAIDs) is widespread to reduce the pain associated with osteoarthritis; however the sideeffects of these drugs can be severe, sometimes leading to gastro-intestinal ulcer complications which account for around 7000 US and 1000 UK deaths each year. The development of Cyclo-oxygenase 2 (COX2)-selective inhibitors should reduce these ulcer complications, but evidence is limited, and the possibility that COX2 inhibitors increase cardiovascular events has been raised.
TARGET (The Therapeutic Arthritis Research and Gastrointestinal Event Trial) assessed gastrointestinal and cardiovascular safety of the COX2 inhibitor lumiracoxib compared with the NSAIDs naproxen and ibuprofen. 18325 osteoarthritis patients (aged 50 years or older) were randomised to receive either lumiracoxib (9156 patients), naproxen (4754 patients), or ibuprofen (4415 patients) for1 year. The risk of ulcer complications was reduced among patients given lumiracoxib (0·25%) compared with patients using non-selective NSAIDs (1·09%); however this benefit did not apply for patients who were also taking aspirin.
TARGET also demonstrated that the incidence of non-fatal and silent myocardial infarction, stroke, or cardiovascular death, which was low in the population, did not differ significantly between treatment groups (lumiracoxib 0·65% vs NSAIDs 0·55%), or when analysed by aspirin use, age, sex, high cardiovascular risk, or cerebrovascular history. “The fact that we enrolled osteoarthritis patients in the study who already had high blood pressure or other risk factors for coronary heart disease was important,” says Dr. Michael E Farkouh, lead author on the cardiovascular outcomes paper (New York University School of Medicine, USA).
Investigator Michael Doherty (University of Nottingham, UK) comments: “Lumiracoxib showed a three to four-fold reduction in ulcer complications compared with non-steroidal anti-inflammatory drugs without an increase in the rate of serious cardiovascular events, suggesting that lumiracoxib is an appropriate treatment for patients with osteoarthritis”.