Intra-articular injection of hyaluronate (SI-6601D) improves joint pain and synovial fluid prostaglandin E2 levels in rheumatoid arthritis: a multicenter clinical trial.
OBJECTIVE
The relationship between clinicalfeatures and biochemical parameters of synovialfluid after serial intra-articular injections of sodium hyaluronate (SI-6601D) was investigated.


METHODS
SI-6601D (sodium hyaluronate with an average molecular weight of 8.4 x 10(5); 25mg/2.5ml/syringe) was injected intra-articularly into the knees of 25 patients with rheumatoid arthritis (RA) every week for 5 consecutive weeks. Clinical and biochemical parameters were monitored before and after injection. Clinicalfindings included pain, as a summation of 3 categories (pain at rest, pain in motion and pain in passive motion, each assessed on a 4-step rating scale), and inflammation, also as a summation of 3 categories (swelling, patellar ballotement and local warmth, each assessed on a 4-step rating scale). Pain on walking of patient was qualitatively assessed by visual analogue scale (VAS). The aspirated volume of synovialfluid (SFV) was recorded and levels of prostaglandin (PG) E2, transforming growth factor beta-1, tumor necrosis factor alpha, interleukin I receptor antagonist, chondroitin 4-sulfate (C4S) and chondroitin 6-sulfate were measured.


RESULTS
Significant improvement in pain symptoms (p < 0.0001), inflammation (p < 0.0001), VAS pain (p < 0.001) and SFV (p < 0.05) were observed after the 5 injections. Levels of PGE2 (p < 0.05) and C4S (p < 0.05) in the synovialfluid were significantly decreased.


CONCLUSIONS
SI-6601D improved local clinical symptoms in RA patients by suppressing PGE2 and, therefore, may be a useful treatment for local inflammation in RA.
Goto
M
M
Division of Rheumatic Diseases, Tokyo Metropolitan Otsuka Hospital, Japan. m.goto-o@ohtsuka-hospital.toshima.tokyo.jp
Hanyu
T
T
Yoshio
T
T
Matsuno
H
H
Shimizu
M
M
Murata
N
N
Shiozawa
S
S
Matsubara
T
T
Yamana
S
S
Matsuda
T
T
D000203:Activities of Daily Living; D000328:Adult; D000368:Aged; D000818:Animals; D018771:Arthralgia / Q000188:drug therapy*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D002645:Chickens; D002809:Chondroitin Sulfates / Q000378:metabolism; D003129:Comb and Wattles / Q000737:chemistry; D015232:Dinoprostone / Q000378:metabolism*; D005260:Female; D006801:Humans; D006820:Hyaluronic Acid / Q000008:administration & dosage / Q000302:isolation & purification / Q000627:therapeutic use*; D007270:Injections, Intra-Articular; D007596:Joints / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D013582:Synovial Fluid / Q000187:drug effects / Q000378:metabolism*; D013585:Synovitis / Q000188:drug therapy* / Q000503:physiopathology; D016212:Transforming Growth Factor beta / Q000378:metabolism; D053773:Transforming Growth Factor beta1; D016896:Treatment Outcome; D016138:Walking / Q000502:physiology
C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D006820:Hyaluronic Acid; D002809:Chondroitin Sulfates; D015232:Dinoprostone