A study of patients with osteoarthritis (OA) showed that those taking the selective cyclo-oxygenase 2 (COX-2) inhibitor lumiracoxib have three to four times fewer ulcer complications than those taking conventional nonsteroidal anti-inflammatory drugs (NSAIDs), according to findings published in the August 31 issue of The Lancet.

Involving over 18,000 patients, the study showed that those in the lumiracoxib group also had similar rates of cardiovascular events, the authors noted. These findings of the Therapeutic Arthritis Research and Gastrointestinal Event Trial (TARGET) study show the clinical appropriateness of using lumiracoxib in patients with OA, who are often taking aspirin concomitantly as prophylaxis against primary or secondary cardiovascular events and, therefore, are already at risk of medication-related gastrointestinal (GI) complications. The study was funded by Novartis, which manufactures lumiracoxib.

The findings may have implications for other COX-2 inhibitors, or coxibs, according to lead author Thomas J. Schnitzer, MD. "The study supports and extends information regarding the GI safety of coxibs," he told CiaoMed. "The findings clearly provide as extensive a database as available to support the GI safety of lumiracoxib in particular. We also saw no increased cardiovascular risk. The findings show that it's a safe and effective drug to use in patients with osteoarthritis." Dr. Schnitzer is Professor and Dean of Clinical Research at Northwestern University Feinberg School of Medicine in Chicago, Ill.

The investigators wanted to test the GI safety of lumiracoxib in comparison to NSAIDs because two other studies involving coxibs have had conflicting results. In the Celecoxib Long-term Arthritis Safety Study (CLASS), which involved patients with both RA and OA, the findings "failed to show a significant benefit for celecoxib for ... upper gastrointestinal ulcer complications for the full duration of the study," the TARGET authors wrote. In contrast, the Vioxx GI Outcomes Research (VIGOR) study, which involved patients with RA, "showed a significant benefit for rofecoxib for ... clinical upper gastrointestinal events."

Therefore, the current study recruited 18,325 OA patients who were at least 50 years old and randomized the patients as follows: 9156 received 400 mg of lumiracoxib once daily; 4754 received 500 mg of naproxen twice daily; and 4415 received 800 mg of ibuprofen twice daily. The study protocol also stratified patients by low-dose aspirin use and age.

The investigators wanted to assess the difference among the groups in the time to upper gastrointestinal ulcer complications, which were defined as bleeding, perforation, or obstruction. They also wanted to compare the groups' rates of cardiovascular events, which were defined as myocardial infarction, stroke, or cardiovascular death.

Among these patients, 81 (0.44 percent) never started treatment and 7120 (39 percent) withdrew prematurely. Among nonaspirin users, the cumulative one-year incidence of ulcer complications was 1.09 percent among patients taking NSAIDs, with 64 events. For such in the lumiracoxib group, the ulcer complication rate was 0.25 percent, with 14 events (P <.0001). Similarly, in the overall population, the lumiracoxib group had significantly fewer ulcer complications compared to those taking NSAIDs (P <.0001).

However, this difference was not present in those taking aspirin, the authors reported. Among aspirin takers, there was no significant difference between lumiracoxib and NSAID patients (P = 0.4876).

The groups had similar rates of cardiovascular complications, the authors noted. In the overall population, 50 of the 9127 patients in the combined NSAID groups (0.55 percent) reached the cardiovascular endpoint. Among the 9117 lumiracoxib patients for whom data were available, 59 (0.65 percent) reached this endpoint (P = .5074).

Leading OA experts and CiaoMed editorial board members shared their perspectives on the importance and limitations of the TARGET study's findings.

Leslie J. Crofford, MD, pointed out to CiaoMed that the study was "not sized for cardiovascular endpoints," noting also that "the study population [was] not representative of a high-risk population." Dr. Crofford added that TARGET should be viewed in the context of VIGOR and CLASS, and noted that TARGET was similar to CLASS "in that aspirin cotreatment eliminated GI protection." Dr. Crofford is Associate Professor of Internal Medicine in the Division of Rheumatology at the University of Michigan in Ann Arbor, Mich.

"TARGET is by far the largest outcome trial in the NSAID field, with over 18,000 OA patients randomized to receive lumiracoxib, naproxen, or ibuprofen," Carlo Patrono, MD, told CiaoMed. "It is also the first study to demonstrate convincingly a significant reduction ... in ulcer complications ... with lumiracoxib vs NSAIDs in the overall population that included both low-dose aspirin and nonusers." Dr. Patrono is Professor and Chair of Pharmacology at the University of Rome in Rome, Italy.

The results of TARGET "help [in] interpreting the apparently conflicting results of CLASS and VIGOR, both in terms of GI and [cardiovascular] safety," he added.

Reference

Schnitzer TJ, Burmester GR, Mysler E, et al., on behalf of the TARGET Study Group. Comparison of lumiracoxib with naproxen and ibuprofen in the Therapeutic Arthritis Research and Gastrointestinal Event Trial (TARGET), reduction in ulcer complications: randomised controlled trial. Lancet. 2004;364:665–674.