BMJ 2002;325:619 ( 21 September )

Papers

Efficacy, tolerability, and upper gastrointestinal safety of celecoxib for treatment of osteoarthritis and rheumatoid arthritis: systematic review of randomised controlled trials

Editorial by Jones
See also p 624

Jonathan J Deeks, senior medical statistician, ^a Lesley A Smith, research fellow, ^a Matthew D Bradley, associate director. ^b

^a Centre for Statistics in Medicine, Institute of Health Sciences, Headington, Oxford OX3 7LF, ^b Pfizer Global Research and Development, Sandwich, Kent CT13 9NJ

Correspondence to: J J Deeks
jon.deeks{at}cancer.org.uk

Objective: To determine the efficacy, gastrointestinal safety, and tolerability of celecoxib (a cyclo-oxygenase 2 (COX 2) inhibitor) used in the treatment of osteoarthritis and rheumatoid arthritis.
Design: Systematic review of randomised trials that compared at least 12 weeks' celecoxib treatment with another non-steroidal anti-inflammatory drug (NSAID) or placebo and reported efficacy, tolerability, or safety. Trials identified from manufacturer and by searching electronic databases and evaluated according to predefined inclusion and quality criteria. Data combined through meta-analysis.
Participants: 15 187 patients with osteoarthritis or rheumatoid arthritis.
Main outcome measures: Efficacy: Western Ontario and McMaster universities osteoarthritis index; American College of Rheumatology responder index and joint scores for rheumatoid arthritis. Tolerability: withdrawal rates for adverse effects. Gastrointestinal safety: incidence of ulcers, bleeds, perforations, and obstructions.
Results: Nine randomised controlled trials were included. Celecoxib and NSAIDS were equally effective for all efficacy outcomes. Compared with those taking other NSAIDs, in patients taking celecoxib the rate of withdrawals due to adverse gastrointestinal events was 46% lower (95% confidence interval 29% to 58%; NNT 35 at three months), the incidence of ulcers detectable by endoscopy was 71% lower (59% to 79%; NNT 6 at three months), and the incidence of symptoms of ulcers, perforations, bleeds, and obstructions was 39% lower (4% to 61%; NNT 208 at six months). Subgroup analysis of patients taking aspirin showed that the incidence of ulcers detected by endoscopy was reduced by 51% (14% to 72%) in those given celecoxib compared with other NSAIDs. The reduction was greater (73%, 52% to 84%) in those not taking aspirin.
Conclusion: Celecoxib is as effective as other NSAIDs for relief of symptoms of osteoarthritis and rheumatoid arthritis and has significantly improved gastrointestinal safety and tolerability.

What is already known on this topic Long term NSAID use is associated with the development of peptic and duodenal ulcers COX 2 specific inhibitors are claimed to cause fewer gastrointestinal complications The National Institute for Clinical Excellence has recently recommended that COX 2 specific inhibitors are used in patients with arthritis who are at risk of gastrointestinal complications but not in those taking prophylactic aspirin What this study adds Systematic review of randomised trials shows that celecoxib is as effective as other NSAIDs for osteoarthritis and rheumatoid arthritis Celecoxib has significantly improved gastrointestinal safety and tolerability compared with standard NSAIDs An improvement in gastrointestinal safety was still evident in patients who were also taking aspirin

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