Effects of nimesulide on pain and on synovial fluid concentrations of substance P, interleukin-6 and interleukin-8 in patients with knee osteoarthritis: comparison with celecoxib.
OBJECTIVE
This study was designed to investigate the analgesic effects of nimesulide and celecoxib in patients with knee osteoarthritis (OA). In patients with joint effusion, the effects of these non-steroidal anti-inflammatory drugs (NSAIDs) on synovial fluid concentrations of substance P (SP), interleukin (IL)-6 and IL-8 also were evaluated.


METHODS
Patients were randomly assigned either nimesulide (100 mg twice a day) or celecoxib (200 mg once a day) for 2 weeks. The intensity of joint pain was assessed with a 100-mm visual analogue scale (VAS). Furthermore, patients completed questions about analgesic efficacy and overall tolerability of the treatments on a five-point categorical scale. Synovial fluid samples were drawn at baseline, 30 min after the first drug intake (day 1), and 30 min after the last drug intake (day 14).


RESULTS
We enrolled 44 patients, 20 of whom had a joint effusion. In this group, the effects of nimesulide were more marked than for celecoxib, with evidence of a faster onset of the analgesic action. Both after a single or repeated administration, nimesulide significantly reduced the synovial fluid concentrations of SP and IL-6. Celecoxib, on the other hand, did not change the concentrations of SP and significantly reduced the levels of IL-6 only on day 14. None of the drugs affected IL-8. Both drugs were generally well tolerated.


CONCLUSIONS
These results provide evidence that nimesulide is an effective agent for the symptomatic treatment of OA. The effect on inflammatory pain mediators is consistent with the fast analgesic action of this NSAID.
Bianchi
M
M
Department of Pharmacology, University of Milan, Milan, and Unit of Rheumatology, A.O. Ospedale di Circolo e Fondazione Macchi, Varese, Italy. mauro.bianchi@unimi.it
Broggini
M
M
Balzarini
P
P
Franchi
S
S
Sacerdote
P
P
D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D018771:Arthralgia / Q000188:drug therapy*; D000068579:Celecoxib; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D008297:Male; D020370:Osteoarthritis, Knee / Q000188:drug therapy*; D010147:Pain Measurement; D011720:Pyrazoles / Q000627:therapeutic use*; D013373:Substance P / Q000378:metabolism; D013449:Sulfonamides / Q000627:therapeutic use*; D013582:Synovial Fluid / Q000737:chemistry; D016896:Treatment Outcome
D000894:Anti-Inflammatory Agents, Non-Steroidal; D015850:Interleukin-6; D016209:Interleukin-8; D011720:Pyrazoles; D013449:Sulfonamides; D013373:Substance P; D000068579:Celecoxib; C012655:nimesulide