Background Non-steroidal anti-inflammatory drugs (NSAIDs), such as ketoprofen, ibuprofen and diclofenac, are widely used for the management of mild-to-moderate pain, chronic inflammatory and degenerative joint diseases. Recent data on two comparative meta-analyses of randomized controlled trials (RCTs) evaluated the efficacy and safety of orally administered ketoprofen vs ibuprofen and diclofenac.

Objectives The aim of this analysis was to obtain a complete comparative assessment of risk/benefit profile of these NSAIDs, thus merging the information from these two meta-analyses.

Methods The literature was systematically reviewed and the search was restricted to randomized clinical trials comparing directly therapeutic doses of oral ketoprofen (50-200 mg/day) vs ibuprofen (600-1800 mg/day) or diclofenac (75-150 mg/day), published on the main databases (Medline, Cochrane Central and Embase) until July 2013. The study selection was made independently by two rheumatologists in accordance with the Cochrane Collaboration guidelines.

Results A total of 13 RCTs involving 898 patients met the inclusion criteria: eight ketoprofen vs ibuprofen and five comparing ketoprofen vs diclofenac. The majority of the RCTs included patients with systemic rheumatic diseases. The evaluation of the efficacy outcome between ketoprofen and ibuprofen/diclofenac was statistically significant (0.459, 95% CI 0.33-0.58; P=0.00) at all point-estimates of the mean weighted size effect. The test of heterogeneity for the efficacy outcome was not statistically significant (c² =18.07 - df=12 - P=0.1136). Regarding the safety outcome a total of 10 RCTs, involving 826 patients, were included in the statistical analysis. 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-analyses 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 analyzed were not statistically significant for all meta-analyses.

Conclusions These findings support that oral ketoprofen is superior in efficacy than diclofenac/ibuprofen in relieving moderate-severe rheumatic pain and in improving functional status and general conditions, with an overall good safety profile, comparable to ibuprofen and diclofenac. This analysis further confirms that oral ketoprofen has a better risk/benefit profile than ibuprofen and diclofenac.

References

1. Calin A. J Rheumatol. 1977; 4(2):153-157; 19.

2. Mills SB. Br Med J. 1973; 4(5884):82-84; 20.

3. Montrone F. Rheumatol Rehabil. 1979;18(2):114-118.

4. Huskisson EC. Br Med J. 1976 May 1;1(6017):1048-9.

5. Matsumo S. Br J Clin Pract 1981; 35(7-8): 266. 14.

6. Giaccai L. Clin Ter 1978; 84: 375-85.

7. Melisch DR. Clin Pharmacol 1988; 28: S29-33.

8. Hynninen MS. Can J Anaesth 2000; 47: 1182-7.

9. Robbins D. Curr Ther Res 1990;48:780-9.

10. Saxena RP. Curr Med Res Opin 1978;5:484-8.

11. Tai YM. J R Soc Med 1992; 85: 16-8.

12. Boey ML. Singapore Med J. 1988 Jun;29(3):240-5.

13. Cherubino P. Clin Ter. 1983 Dec 31;107(6):471-5.

Disclosure of Interest P. Sarzi-Puttini: None declared, M. Bagnasco Employee of: Dompé farmaceutici, L. Lanata Employee of: Dompé farmaceutici, F. Atzeni: None declared