Background/Purpose: Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used for management of mild-to-moderate pain, chronic inflammatory and degenerative joint diseases. Among NSAIDs, ketoprofen, ibuprofen and diclofenac have been widely used for the last 30 years and particular attention should be taken into account when choosing a NSAIDs in order to achieve the best risk/benefit ratio for patients. Recent publication of our comparative meta-analysis demonstrating that efficacy of oral ketoprofen is greater than ibuprofen and/or diclofenac, raised many questions about safety profile of these molecules. For this reason we performed this meta-analysis of randomised controlled trials (RCTs) in order to compare the safety of orally administered ketoprofen vs ibuprofen and diclofenac and to obtain a complete comparative assessment of risk/benefit profile of these NSAIDs.

Methods: A systematic literature search was performed on main databases (Medline, Cochrane Central and Embase) until July 2013 to identify RCTs comparing directly therapeutic doses of oral ketoprofen (50-200 mg/day) vs ibuprofen (600-1800 mg/day) or diclofenac (75-150 mg/day). In accordance with the Cochrane Collaboration guideline, two rheumatologists carried out independently study selection.

Results: A total of 10 RCTs involving 826 patients met the inclusion criteria. Five of the 10 RCTs included patients with systemic rheumatic diseases. Findings from this meta-analysis did not reveal any difference in safety for ketoprofen compared to ibuprofen and/or diclofenac. The difference between ketoprofen and the pooled ibuprofen/diclofenac data was not statistically significant (risk ratio; RR=1.02, 95% CI 0.78-1.33; P=0.92) at all point-estimates of the mean weighted size effect. Further sub-analysis also confirmed that ketoprofen was not significantly different to either diclofenac (RR=0.86; 95% CI 0.51-1.45; P=0.58) or ibuprofen (RR=1.08; 95% CI 0.79-1.48; P=0.65) at all point-estimates. Heterogeneity for the safety measures analysed were not statistically significant for all meta-analyses.

Conclusion : Findings of this meta-analysis show that ketoprofen is well tolerated, with a safety profile at least comparable to ibuprofen and diclofenac, and no serious AEs. In light of superior efficacy demonstrated in our previous meta-analysis, these further safety results support recommendation that oral ketoprofen has the best risk/benefit profile vs ibuprofen and diclofenac.