PMID- 19530981
OWN - NLM
STAT- MEDLINE
DCOM- 20091104
LR  - 20220330
IS  - 1473-4877 (Electronic)
IS  - 0300-7995 (Linking)
VI  - 25
IP  - 8
DP  - 2009 Aug
TI  - The hepatic safety and tolerability of the cyclooxygenase-2 selective NSAID 
      celecoxib: pooled analysis of 41 randomized controlled trials.
PG  - 1841-51
LID - 10.1185/03007990903018279 [doi]
AB  - OBJECTIVE: To assess the hepatic safety and tolerability of celecoxib versus 
      placebo and three commonly prescribed nonselective nonsteroidal anti-inflammatory 
      drugs (NSAIDs). RESEARCH DESIGN AND METHODS: This was a retrospective, pooled 
      analysis of a 41-study dataset involving patients with osteoarthritis, rheumatoid 
      arthritis, ankylosing spondylitis, chronic low back pain, and Alzheimer's 
      disease. Criteria for selection of studies were: (1) Randomized, parallel-group 
      design and planned treatment duration of > or =2 weeks (2) > or =1 placebo or 
      NSAID comparator (3) > or =1 arm with celecoxib at total daily dose of > or =200 
      mg (4) Data available as of October 31, 2004 Data were pooled by treatment and 
      subject from the safety analysis population of included studies. 
      Treatment-emergent hepatobiliary adverse events (AEs) were compared for celecoxib 
      <200 mg/day (943 patients), 200 mg/day (12 008 patients), 400 mg/day (7380 
      patients), and 800 mg/day (4602 patients); placebo (4057 patients); diclofenac 
      100-150 mg/day (7639 patients); naproxen 1000 mg/day (2953 patients); and 
      ibuprofen 2400 mg/day (2484 patients). Hepatobiliary laboratory abnormalities 
      were also analyzed. RESULTS: There were no cases of liver failure, 
      treatment-related liver transplant, or treatment-related hepatobiliary death. 
      Incidence of serious hepatic AEs was low, with 13 (0.05%) serious hepatic AEs 
      among 24 933 celecoxib-treated patients, and 16 (0.21%) among 7639 
      diclofenac-treated patients. No patients receiving celecoxib or any nonselective 
      NSAID met criteria for Hy's rule (alanine aminotransferase [ALT] > or =3 x upper 
      limit of normal [ULN] with bilirubin > or =2 x ULN). The incidence of notable (> 
      or =5 x ULN) and severe (> or =10 x ULN) ALT elevations was similar for all 
      treatment groups except diclofenac. Significantly fewer hepatobiliary AEs were 
      reported for celecoxib (any dose; 1.11%) than for diclofenac (vs. 4.24%, p < 
      0.0001); for ibuprofen (vs. 1.53%, p = 0.06) and placebo (vs. 0.89%, p = 0.21) 
      the incidence of AEs was comparable to celecoxib. LIMITATIONS: A number of 
      limitations should be considered when evaluating the results: findings were 
      limited by the quality and reporting of the studies selected; difficulty in 
      estimating the incidence of AEs due to the low frequency of events; acetaminophen 
      not included as an active comparator. CONCLUSIONS: In this pooled analysis, the 
      incidence of hepatic AEs in patients treated with celecoxib was similar to that 
      for both placebo-treated patients and patients treated with ibuprofen or 
      naproxen, but lower than for diclofenac.
FAU - Soni, Paresh
AU  - Soni P
AD  - Pfizer Inc, New York, NY 10017, USA.
FAU - Shell, Briton
AU  - Shell B
FAU - Cawkwell, Gail
AU  - Cawkwell G
FAU - Li, Chunming
AU  - Li C
FAU - Ma, Hong
AU  - Ma H
LA  - eng
PT  - Journal Article
PT  - Meta-Analysis
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Curr Med Res Opin
JT  - Current medical research and opinion
JID - 0351014
RN  - 0 (Anti-Inflammatory Agents, Non-Steroidal)
RN  - 0 (Pyrazoles)
RN  - 0 (Sulfonamides)
RN  - EC 1.14.99.1 (Cyclooxygenase 2)
RN  - JCX84Q7J1L (Celecoxib)
SB  - IM
MH  - Aged
MH  - Anti-Inflammatory Agents, Non-Steroidal/*adverse effects/metabolism/pharmacology
MH  - Celecoxib
MH  - Cyclooxygenase 2/*adverse effects/metabolism/pharmacology
MH  - *Drug Tolerance
MH  - Female
MH  - Humans
MH  - Liver/*drug effects
MH  - Male
MH  - Middle Aged
MH  - Musculoskeletal Diseases/drug therapy
MH  - Pyrazoles/*adverse effects/metabolism/pharmacology
MH  - Randomized Controlled Trials as Topic
MH  - Retrospective Studies
MH  - Sulfonamides/*adverse effects/metabolism/pharmacology
EDAT- 2009/06/18 09:00
MHDA- 2009/11/05 06:00
CRDT- 2009/06/18 09:00
PHST- 2009/06/18 09:00 [entrez]
PHST- 2009/06/18 09:00 [pubmed]
PHST- 2009/11/05 06:00 [medline]
AID - 10.1185/03007990903018279 [doi]
PST - ppublish
SO  - Curr Med Res Opin. 2009 Aug;25(8):1841-51. doi: 10.1185/03007990903018279.