PMID- 11041909
OWN - NLM
STAT- MEDLINE
DCOM- 20001121
LR  - 20190813
IS  - 0003-9926 (Print)
IS  - 0003-9926 (Linking)
VI  - 160
IP  - 19
DP  - 2000 Oct 23
TI  - Gastrointestinal tolerability of the selective cyclooxygenase-2 (COX-2) inhibitor 
      rofecoxib compared with nonselective COX-1 and COX-2 inhibitors in 
      osteoarthritis.
PG  - 2998-3003
AB  - BACKGROUND: Most nonsteroidal anti-inflammatory drugs (NSAIDs) are nonselective 
      cyclooxygenase (COX-1 and COX-2) inhibitors and are associated with a variety of 
      upper gastrointestinal (GI) tract symptoms. The roles of COX-1 and COX-2 in the 
      pathogenesis of these symptoms are unclear. To test whether COX-2 inhibition with 
      rofecoxib would have greater GI tolerability than nonselective COX-1 and COX-2 
      inhibition, we compared the incidences of (1) treatment discontinuations for GI 
      adverse events (AEs) and (2) prespecified dyspeptic-type GI AEs among patients 
      with osteoarthritis treated with rofecoxib vs NSAIDs. METHODS: A prespecified, 
      combined analysis of investigator-reported GI AEs in all 8 double-blind, 
      randomized, phase 2b/3 osteoarthritis trials of rofecoxib was conducted. Patients 
      included men and women with osteoarthritis (N = 5435); there was no upper age 
      limit for entry. Treatments tested included rofecoxib, 12.5, 25, or 50 mg 
      (combined), vs ibuprofen, diclofenac, or nabumetone (combined). Primary outcomes 
      were the time (by survival analysis) to (1) treatment discontinuation due to GI 
      AEs and (2) first reported dyspeptic-type GI AE. Between-treatment comparisons 
      were made by log-rank test. RESULTS: The number of treatment discontinuations 
      caused by GI AEs during 12 months was significantly lower (P=.02) with rofecoxib 
      vs NSAIDs (8.2 vs 12.0 per 100 patient-years; relative risk, 0.70; 95% confidence 
      interval, 0.52-0.94). The incidence of prespecified dyspeptic-type GI AEs during 
      the first 6 months was significantly lower (P=.02) with rofecoxib vs NSAIDs (69.3 
      vs 85.2 per 100 patient-years; relative risk, 0.85; 95% confidence interval, 
      0.74-0.97). However, the difference between treatments in dyspeptic-type GI AEs 
      was attenuated after 6 months. CONCLUSION: Rofecoxib was associated with a lower 
      incidence of treatment discontinuations due to GI AEs over 12 months and a lower 
      incidence of dyspeptic-type GI AEs over 6 months than treatment with nonselective 
      COX inhibitors, or NSAIDs. Arch Intern Med. 2000;160:2998-3003
FAU - Watson, D J
AU  - Watson DJ
AD  - Merck Research Labs, West Point, PA, USA.
FAU - Harper, S E
AU  - Harper SE
FAU - Zhao, P L
AU  - Zhao PL
FAU - Quan, H
AU  - Quan H
FAU - Bolognese, J A
AU  - Bolognese JA
FAU - Simon, T J
AU  - Simon TJ
LA  - eng
PT  - Journal Article
PT  - Meta-Analysis
PL  - United States
TA  - Arch Intern Med
JT  - Archives of internal medicine
JID - 0372440
RN  - 0 (Anti-Inflammatory Agents, Non-Steroidal)
RN  - 0 (Cyclooxygenase 2 Inhibitors)
RN  - 0 (Cyclooxygenase Inhibitors)
RN  - 0 (Isoenzymes)
RN  - 0 (Lactones)
RN  - 0 (Membrane Proteins)
RN  - 0 (Sulfones)
RN  - 0QTW8Z7MCR (rofecoxib)
RN  - EC 1.14.99.1 (Cyclooxygenase 1)
RN  - EC 1.14.99.1 (Cyclooxygenase 2)
RN  - EC 1.14.99.1 (PTGS1 protein, human)
RN  - EC 1.14.99.1 (PTGS2 protein, human)
RN  - EC 1.14.99.1 (Prostaglandin-Endoperoxide Synthases)
SB  - IM
MH  - Abdominal Pain/chemically induced
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Anti-Inflammatory Agents, Non-Steroidal/therapeutic use
MH  - Clinical Trials, Phase II as Topic
MH  - Clinical Trials, Phase III as Topic
MH  - Cyclooxygenase 1
MH  - Cyclooxygenase 2
MH  - Cyclooxygenase 2 Inhibitors
MH  - Cyclooxygenase Inhibitors/*adverse effects
MH  - Dyspepsia/*chemically induced
MH  - Female
MH  - Humans
MH  - Isoenzymes/antagonists & inhibitors
MH  - Lactones/*adverse effects
MH  - Male
MH  - Membrane Proteins
MH  - Middle Aged
MH  - Osteoarthritis/*drug therapy
MH  - Prostaglandin-Endoperoxide Synthases/*metabolism
MH  - Randomized Controlled Trials as Topic
MH  - Sulfones
EDAT- 2000/10/21 11:00
MHDA- 2001/02/28 10:01
CRDT- 2000/10/21 11:00
PHST- 2000/10/21 11:00 [pubmed]
PHST- 2001/02/28 10:01 [medline]
PHST- 2000/10/21 11:00 [entrez]
AID - ioi90757 [pii]
AID - 10.1001/archinte.160.19.2998 [doi]
PST - ppublish
SO  - Arch Intern Med. 2000 Oct 23;160(19):2998-3003. doi: 
      10.1001/archinte.160.19.2998.