BACKGROUND: Based on the experience with selective cyclooxygenase (COX)-2 inhibitors, including rofecoxib, valdecoxib, and celecoxib, it was anticipated that etoricoxib, a new selective COX-2 inhibitor, would display mechanism-based, dose-dependent renal adverse effects (AEs) similar to those observed with nonselective non-steroidal anti-inflammatory drugs (NSAIDs) in long-term treatment. OBJECTIVE: The present analysis examined pooled safety data from the etoricoxib clinical development program with the aim of comparing the renal AE profiles of etoricoxib 60, 90, and 120 mg/d with those of approved therapeutic dosages of the comparator nonselective NSAIDs, naproxen 1000 mg/d and ibuprofen 2400 mg/d, and with that of placebo. METHODS: The etoricoxib program database included data from 8 placebo-controlled Phase III studies of osteoarthritis, rheumatoid arthritis, and chronic low back pain. As part of the program-wide assessment of etoricoxib, the investigator-reported incidence of and discontinuations due to renal AEs, including hypertension, lower-extremity edema (LEE), elevated serum creatinine concentration (SCC), and congestive heart failure (CHF) were examined. RESULTS: Data from 4770 patients were included in the analysis. Most patients were women (69.0%-80.3%), and most were white (68.0%-83.3%). The mean (SD) age at baseline ranged from 53.6 (12.1) to 62.2 (8.4) years. Overall, the incidence of renal AEs was low and generally similar between the active-treatment groups. In the placebo; etoricoxib 60-, 90-, and 120-mg; naproxen, and ibuprofen groups, the incidences of hypertension were 2.0%, 4.0%, 3.4%, 4.7%, 2.9%, and 6.6%, respectively, and the incidences of LEE were 1.9%, 3.2%, 1.5%, 1.3%, 2.3%, and 1.8%, respectively. The only significant difference found was the incidence of hypertension with etoricoxib 90 mg/d versus that with placebo (P=0.001); however, the rates of hypertension observed with etoricoxib at any dosage were not clinically meaningfully different versus comparator NSAIDs. Also, LEE was rarely of clinical significance with etoricoxib or comparator NSAIDs; related discontinuations were infrequent in all treatment groups. In addition, the incidences of elevated SCC and CHF were low among active-treatment groups (0.0% to 0.8% and 0.0% to 0.2%, respectively). CONCLUSIONS: Based on this combined data review, the risks for renal AEs (i.e., hypertension, LEE, elevated SCC changes, and CHF) with etoricoxib 60, 90, and 120 mg/d were low, with a shallow dose response, and were generally similar to those found with the comparator NSAIDs naproxen 1000 mg/d and ibuprofen 2400 mg/d.
RCT Entities:
BACKGROUND: Based on the experience with selective cyclooxygenase (COX)-2 inhibitors, including rofecoxib, valdecoxib, and celecoxib, it was anticipated that etoricoxib, a new selective COX-2 inhibitor, would display mechanism-based, dose-dependent renal adverse effects (AEs) similar to those observed with nonselective non-steroidal anti-inflammatory drugs (NSAIDs) in long-term treatment. OBJECTIVE: The present analysis examined pooled safety data from the etoricoxib clinical development program with the aim of comparing the renal AE profiles of etoricoxib 60, 90, and 120 mg/d with those of approved therapeutic dosages of the comparator nonselective NSAIDs, naproxen 1000 mg/d and ibuprofen 2400 mg/d, and with that of placebo. METHODS: The etoricoxib program database included data from 8 placebo-controlled Phase III studies of osteoarthritis, rheumatoid arthritis, and chronic low back pain. As part of the program-wide assessment of etoricoxib, the investigator-reported incidence of and discontinuations due to renal AEs, including hypertension, lower-extremity edema (LEE), elevated serum creatinine concentration (SCC), and congestive heart failure (CHF) were examined. RESULTS: Data from 4770 patients were included in the analysis. Most patients were women (69.0%-80.3%), and most were white (68.0%-83.3%). The mean (SD) age at baseline ranged from 53.6 (12.1) to 62.2 (8.4) years. Overall, the incidence of renal AEs was low and generally similar between the active-treatment groups. In the placebo; etoricoxib 60-, 90-, and 120-mg; naproxen, and ibuprofen groups, the incidences of hypertension were 2.0%, 4.0%, 3.4%, 4.7%, 2.9%, and 6.6%, respectively, and the incidences of LEE were 1.9%, 3.2%, 1.5%, 1.3%, 2.3%, and 1.8%, respectively. The only significant difference found was the incidence of hypertension with etoricoxib 90 mg/d versus that with placebo (P=0.001); however, the rates of hypertension observed with etoricoxib at any dosage were not clinically meaningfully different versus comparator NSAIDs. Also, LEE was rarely of clinical significance with etoricoxib or comparator NSAIDs; related discontinuations were infrequent in all treatment groups. In addition, the incidences of elevated SCC and CHF were low among active-treatment groups (0.0% to 0.8% and 0.0% to 0.2%, respectively). CONCLUSIONS: Based on this combined data review, the risks for renal AEs (i.e., hypertension, LEE, elevated SCC changes, and CHF) with etoricoxib 60, 90, and 120 mg/d were low, with a shallow dose response, and were generally similar to those found with the comparator NSAIDs naproxen 1000 mg/d and ibuprofen 2400 mg/d.
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