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BMJ (Clinical Research Ed.) Dec 2004To estimate the analgesic efficacy of non-steroidal anti-inflammatory drugs (NSAIDs), including selective cyclo-oxygenase-2 inhibitors (coxibs), in patients with... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To estimate the analgesic efficacy of non-steroidal anti-inflammatory drugs (NSAIDs), including selective cyclo-oxygenase-2 inhibitors (coxibs), in patients with osteoarthritis of the knee.
DESIGN
Systematic review and meta-analysis of randomised placebo controlled trials.
STUDIES REVIEWED
23 trials including 10 845 patients, median age of 62.5 years. 7807 patients received adequate doses of NSAIDs and 3038 received placebo. The mean weighted baseline pain score was 64.2 mm on 100 mm visual analogue scale (VAS), and average duration of symptoms was 8.2 years.
MAIN OUTCOME MEASURE
Change in overall intensity of pain.
RESULTS
Methodological quality of trials was acceptable, but 13 trials excluded patients before randomisation if they did not respond to NSAIDs. One trial provided long term data for pain that showed no significant effect of NSAIDs compared with placebo at one to four years. The pooled difference for pain on visual analogue scale in all included trials was 10.1 mm (95% confidence interval 7.4 to 12.8) or 15.6% better than placebo after 2-13 weeks. The results were heterogeneous, and the effect size for pain reduction was 0.32 (0.24 to 0.39) in a random effects model. In 10 trials that did not exclude non-responders to NSAID treatment the results were homogeneous, with an effect size for pain reduction of 0.23 (0.15 to 0.31).
CONCLUSION
NSAIDs can reduce short term pain in osteoarthritis of the knee slightly better than placebo, but the current analysis does not support long term use of NSAIDs for this condition. As serious adverse effects are associated with oral NSAIDs, only limited use can be recommended.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors; Disabled Persons; Humans; Isoenzymes; Membrane Proteins; Middle Aged; Osteoarthritis, Knee; Pain; Prostaglandin-Endoperoxide Synthases; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 15561731
DOI: 10.1136/bmj.38273.626655.63 -
BMJ (Clinical Research Ed.) Oct 2004To assess the effectiveness of five gastroprotective strategies for people taking non-steroidal anti-inflammatory drugs (NSAIDs)--H2 receptor antagonists plus... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
To assess the effectiveness of five gastroprotective strategies for people taking non-steroidal anti-inflammatory drugs (NSAIDs)--H2 receptor antagonists plus non-selective (or cyclo-oxygenase-1) NSAIDs; proton pump inhibitors plus non-selective NSAIDs; misoprostol plus non-selective NSAIDs; COX-2 selective NSAIDs; or COX-2 specific NSAIDs--in reducing serious gastrointestinal complications, symptomatic ulcers, serious cardiovascular or renal disease, and deaths, and improving quality of life.
DATA SOURCES
The Cochrane Library, Medline, Embase, Current Controlled Trials, and System for Information on Grey Literature in Europe (SIGLE) were searched to May 2002. Bibliographies and author contacts were used to identify further studies; non-English articles were included.
REVIEW METHODS
Trial selection, data extraction, and quality assessment were performed independently, in duplicate. Articles were rejected only if the study was not a randomised controlled trial; did not assess a gastroprotective strategy versus placebo; included exclusively children or healthy volunteers; lasted less than 21 days; or no review outcomes were measured. Quality assessment included allocation concealment and baseline similarity. Random effects meta-analysis, meta-regression and subgrouping were used to pool effects and analyse associations with length of follow up, mean age, and baseline gastrointestinal status. Heterogeneity was examined and sensitivity analyses performed.
RESULTS
Of 112 included randomised controlled trials (74 666 participants), five were judged to be at low risk of bias, and 138 deaths and 248 serious gastrointestinal events were reported overall. On comparing gastroprotective strategies versus placebo we found no evidence of effectiveness of H2 receptor antagonists for any primary outcomes (few events reported); proton pump inhibitors may reduce the risk of symptomatic ulcers (relative risk 0.09, 95% confidence interval 0.02 to 0.47); misoprostol reduces the risk of serious gastrointestinal complications (0.57, 0.36 to 0.91) and symptomatic ulcers (0.36, 0.20 to 0.67); COX-2 selectives reduce the risk of symptomatic ulcers (0.41, 0.26 to 0.65) and COX-2 specifics reduce the risk of symptomatic ulcers (0.49, 0.38 to 0.62) and possibly serious gastrointestinal complications (0.55, 0.38 to 0.80). All strategies except COX-2 selectives reduce the risk of endoscopic ulcers (at least 3 mm in diameter).
CONCLUSIONS
Misoprostol, COX-2 specific and selective NSAIDs, and probably proton pump inhibitors significantly reduce the risk of symptomatic ulcers, and misoprostol and probably COX-2 specifics significantly reduce the risk of serious gastrointestinal complications, but data quality is low. More data on H2 receptor antagonists and proton pump inhibitors are needed, as is better reporting of rare but important outcomes.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors; Gastrointestinal Diseases; Humans; Isoenzymes; Membrane Proteins; Prostaglandin-Endoperoxide Synthases; Proton Pump Inhibitors; Randomized Controlled Trials as Topic; Risk Factors
PubMed: 15475342
DOI: 10.1136/bmj.38232.680567.EB -
Annals of Internal Medicine May 2003Rofecoxib and celecoxib (coxibs) effectively treat chronic arthritis pain and reduce ulcer complications by 50% compared with nonselective nonsteroidal anti-inflammatory... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Rofecoxib and celecoxib (coxibs) effectively treat chronic arthritis pain and reduce ulcer complications by 50% compared with nonselective nonsteroidal anti-inflammatory drugs (NSAIDs). However, their absolute risk reduction is small and the cost-effectiveness of treatment is uncertain.
OBJECTIVE
To determine whether the degree of risk reduction in gastrointestinal complications by coxibs offsets their increased cost compared with a generic nonselective NSAID.
DESIGN
Cost-utility analysis.
DATA SOURCES
Systematic review of MEDLINE and published abstracts.
TARGET POPULATION
Patients with osteoarthritis or rheumatoid arthritis who are not taking aspirin and who require long-term NSAID therapy for moderate to severe arthritis pain.
PERSPECTIVE
Third-party payer.
INTERVENTIONS
Naproxen, 500 mg twice daily, and coxib, once daily. Patients intolerant of naproxen were switched to a coxib.
TIME HORIZON
Lifetime.
OUTCOME MEASURES
Incremental cost per quality-adjusted life-year (QALY) gained.
RESULTS OF BASE-CASE ANALYSIS
Using a coxib instead of a nonselective NSAID in average-risk patients cost an incremental 275 809 dollars per year to gain 1 additional QALY.
RESULTS OF SENSITIVITY ANALYSIS
The incremental cost per QALY gained decreased to 55 803 dollars when the analysis was limited to the subset of patients with a history of bleeding ulcers. The coxib strategy became dominant when the cost of coxibs was reduced by 90% of the current average wholesale price. In probabilistic sensitivity analysis, if a third-party payer was willing to pay 150 000 dollars per QALY gained, then 4.3% of average-risk patients would fall within the budget.
CONCLUSIONS
The risk reduction seen with coxibs does not offset their increased costs compared with nonselective NSAIDs in the management of average-risk patients with chronic arthritis. However, coxibs may provide an acceptable incremental cost-effectiveness ratio in the subgroup of patients with a history of bleeding ulcers.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Cardiovascular Diseases; Celecoxib; Chronic Disease; Cost-Benefit Analysis; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors; Decision Support Techniques; Humans; Isoenzymes; Lactones; Membrane Proteins; Osteoarthritis; Peptic Ulcer; Prostaglandin-Endoperoxide Synthases; Pyrazoles; Quality-Adjusted Life Years; Recurrence; Risk Factors; Sensitivity and Specificity; Sulfonamides; Sulfones
PubMed: 12755551
DOI: 10.7326/0003-4819-138-10-200305200-00007