ab1904

Intra-articular injection of hyaluronate (SI-6601D) improves joint pain and synovial fluid prostaglandin E2 levels in rheumatoid arthritis: A multicenter clinical trial

M. Goto¹, T. Hanyu², T. Yoshio³, H. Matsuno⁴, M. Shimizu⁵, N. Murata⁶, S. Shiozawa⁷, T. Matsubara⁸, S. Yamana⁹, T. Matsuda¹⁰

¹Division of Rheumatic Diseases, Tokyo Metropolitan Otsuka Hospital, Tokyo; ²Department of Orthopaedic Surgery, Niigata University School of Medicine, Niigata; ³Division of Clinical Immunology, Jichi-Medical School, Tochigi; ⁴Department of Orthopaedic Surgery, Toyama Medical and Pharmaceutical University, Toyama; ⁵Second Department of Internal Medicine and ⁶Department of Orthopaedic Surgery, Osaka Minami National Hospital, Kawachinagano; ⁷Third Department of Internal Medicine, Kobe University School of Medicine, Kobe; ⁸Division of Orthopaedics, Matsubara Clinic, Kobe; ⁹Internal Medicine, Higashi Hiroshima Memorial Hospital, Higashi Hiroshima; ¹⁰Center for the Rheumatic Diseases, Kagoshima Red Cross Hospital, Kagoshima, Japan.

ABSTRACT
Objective
The relationship between clinical features and biochemical parameters of synovial fluid 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 10⁵; 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. Clinical findings 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 synovial fluid (SFV) was recorded and levels of prostaglandin (PG) E2, transforming growth factor beta-1, tumor necrosis factor alpha, interleukin 1 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 synovial fluid were significantly decreased.

Discussion
SI-6601D improved local clinical symptoms in RA patients by suppressing PGE2 and, therefore, may be a useful treatment for local inflammation in RA.

Key words
Hyaluronate, PGE2, rheumatoid arthritis, synovial fluid.

Presented in part at the 62nd National Scientific Meeting of the American College of Rheumatology, San Diego, CA, November, 1998

Please address correspondence and reprint requests to: Makato Goto, MD, PhD, Director, Division of Rheumatic Diseases, Tokyo Metropolitan Otsuka Hospital, 2-8-1 Minami-Otsuka, Toshima-ku, Tokyo 170-0005, Japan.
E-mail: m.goto-o@ohtsuka-hospital.toshima.tokyo.jp