Celecoxib for rheumatoid arthritis

Rheumatoid arthritis (RA) is a systemic auto-immune disorder, involving persistent joint inflammation. NSAIDs are used to control the symptoms of RA, but are associated with significant gastro-intestinal toxicity, including a risk of potentially life threatening gastroduodenal perforations, ulcers and bleeds. The NSAIDs known as the selective Cox II inhibitors, of which celecoxib is a member, were developed in order to reduce the GI toxicity, but are more expensive.

To establish the efficacy and safety of celecoxib in the management of RA by systematic review of available evidence.

We searched the following databases up to August 2002: MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Cochrane Controlled Trials Register, National Research Register, NHS Economic Evaluation Database, Health Technology Assessment Database. The bibliographies of retrieved papers and content experts were consulted for additional references.

All eligible randomised controlled trials (RCTs) were included. No unpublished RCTs were included in this edition of the review.

Data were abstracted independently by two reviewers. Data was analysed using a fixed effects model. A validated checklist was used to score the quality of the RCTs. The planned analysis was to pool, where appropriate continuous outcomes using mean differences and dichotomous outcomes using relative risk ratios. This was not however possible due to the lack of data.

Five RCTs were included (4465 participants); three of the studies also enrolled individuals with OA. The comparators were placebo, naproxen, diclofenac and ibuprofen. The evidence reviewed suggests that celecoxib controls the symptoms of RA to a similar degree to that of the active comparators examined (naproxen, diclofenac and ibuprofen). When compared to placebo, the percentage of patients showing improvement according to ACR 20 criteria at week 4 were 42/82 (51%) in the twice daily celecoxib 200mg group and 43/82 (52%) in the twice daily celecoxib 400mg group; these were significantly different from the placebo group in which 25/85 (29%) improved. The six month data reviewed support a reduced rate of UGI complications with celecoxib but there is also evidence to suggest that these benefits may not be evident in the long-term and that celecoxib offers no additional benefit in patients who are also receiving cardio-prophylactic low dose aspirin.

For an individual with RA the potential benefits of celecoxib need to be balanced against the uncertainty that the short-term reduced incidence of upper GI complications are maintained in the long-term and its increased cost in comparison to traditional NSAIDs.