PMID- 14996519
OWN - NLM
STAT- MEDLINE
DCOM- 20040528
LR  - 20190922
IS  - 0149-2918 (Print)
IS  - 0149-2918 (Linking)
VI  - 26
IP  - 1
DP  - 2004 Jan
TI  - Renal effects of etoricoxib and comparator nonsteroidal anti-inflammatory drugs 
      in controlled clinical trials.
PG  - 70-83
AB  - 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.
FAU - Curtis, Sean P
AU  - Curtis SP
AD  - Department of Clinical Research, Merck Research Laboratories, Rahway, New Jersey 
      07065, USA. sean_curtis@merck.com
FAU - Ng, Jennifer
AU  - Ng J
FAU - Yu, Qinfen
AU  - Yu Q
FAU - Shingo, Sumiko
AU  - Shingo S
FAU - Bergman, Gina
AU  - Bergman G
FAU - McCormick, Calogera L
AU  - McCormick CL
FAU - Reicin, Alise S
AU  - Reicin AS
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Clin Ther
JT  - Clinical therapeutics
JID - 7706726
RN  - 0 (Anti-Inflammatory Agents, Non-Steroidal)
RN  - 0 (Cyclooxygenase Inhibitors)
RN  - 0 (Pyridines)
RN  - 0 (Sulfones)
RN  - WRX4NFY03R (Etoricoxib)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Anti-Inflammatory Agents, Non-Steroidal/*adverse effects
MH  - Clinical Trials, Phase III as Topic
MH  - Cyclooxygenase Inhibitors/administration & dosage/adverse effects
MH  - Dose-Response Relationship, Drug
MH  - Etoricoxib
MH  - Female
MH  - Humans
MH  - Kidney Diseases/chemically induced
MH  - Male
MH  - Middle Aged
MH  - Pyridines/administration & dosage/*adverse effects
MH  - Sulfones/administration & dosage/*adverse effects
EDAT- 2004/03/05 05:00
MHDA- 2004/05/29 05:00
CRDT- 2004/03/05 05:00
PHST- 2003/10/23 00:00 [accepted]
PHST- 2004/03/05 05:00 [pubmed]
PHST- 2004/05/29 05:00 [medline]
PHST- 2004/03/05 05:00 [entrez]
AID - S0149291804900070 [pii]
AID - 10.1016/s0149-2918(04)90007-0 [doi]
PST - ppublish
SO  - Clin Ther. 2004 Jan;26(1):70-83. doi: 10.1016/s0149-2918(04)90007-0.