Intra-articular injections of 750 kD hyaluronan in the treatment of osteoarthritis: a randomised single centre double-blind placebo-controlled trial of 91 patients demonstrating lack of efficacy.

E B Henderson, E C Smith, F Pegley, D R Blake

Inflammation Group, Clinical Studies Division, Royal London Hospital Medical College, United Kingdom.

OBJECTIVE--To determine the safety and efficacy of intra-articular injections of hyaluronan in the treatment of osteoarthritis of the knee. METHODS--A randomised double-blind placebo-controlled trial was carried out on 91 patients with radiologically confirmed osteoarthritis of the knee who were recruited from the outpatient clinics. RESULTS--It was found that weekly intraarticular injections of 20 mg of hyaluronan of M(r) = 750,000 (Hyalgan) in 2 ml of buffered saline performed no better than the inert vehicle alone over a five week period. The principal side effects of a transient increase in pain and swelling in the affected knee was observed in 47% of the treatment group compared with 22% of the placebo group. A few patients with radiologically mild disease treated with Hyalgan appeared to experience medium to long-term symptomatic improvement over matched placebo controls as judged by a delayed return to previous NSAID therapy or analgesia other than paracetamol. Patient numbers in the survival groups, however, were too small to be meaningful. CONCLUSION--It is concluded that intraarticular administration of this preparation of 750 kD hyaluronan offers no significant benefit over placebo during a five week treatment period, but incurs a significantly higher morbidity, and therefore has no place in the routine treatment of osteoarthritis.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

• Becker, L. C., Bergfeld, W. F., Belsito, D. V., Klaassen, C. D., Marks, J. G. Jr, Shank, R. C., Slaga, T. J., Snyder, P. W., Cosmetic Ingredient Review Expert Panel, , Andersen, F. A. (2009). Final Report of the Safety Assessment of Hyaluronic Acid, Potassium Hyaluronate, and Sodium Hyaluronate. International Journal of Toxicology 28: 5-67 [Abstract] [Full Text]  
• Ottaviani, R. A., Wooley, P., Song, Z., Markel, D. C. (2007). Inflammatory and Immunological Responses to Hyaluronan Preparations. Study of a Murine Biocompatibility Model. JBJS 89: 148-157 [Abstract] [Full Text]  
• Arrich, J., Piribauer, F., Mad, P., Schmid, D., Klaushofer, K., Mullner, M. (2005). Intra-articular hyaluronic acid for the treatment of osteoarthritis of the knee: systematic review and meta-analysis. CMAJ 172: 1039-1043 [Abstract] [Full Text]  
• Pham, T, Le Henanff, A, Ravaud, P., Dieppe, P, Paolozzi, L, Dougados, M (2004). Evaluation of the symptomatic and structural efficacy of a new hyaluronic acid compound, NRD101, in comparison with diacerein and placebo in a 1 year randomised controlled study in symptomatic knee osteoarthritis. Ann Rheum Dis 63: 1611-1617 [Abstract] [Full Text]  
• Wang, C.-T., Lin, J., Chang, C.-J., Lin, Y.-T., Hou, S.-M. (2004). Therapeutic Effects of Hyaluronic Acid on Osteoarthritis of the Knee. A Meta-Analysis of Randomized Controlled Trials. JBJS 86: 538-545 [Abstract] [Full Text]  
• Lo, G. H., LaValley, M., McAlindon, T., Felson, D. T. (2003). Intra-articular Hyaluronic Acid in Treatment of Knee Osteoarthritis: A Meta-analysis. JAMA 290: 3115-3121 [Abstract] [Full Text]  
• Karlsson, J., Sjogren, L. S., Lohmander, L. S. (2002). Comparison of two hyaluronan drugs and placebo in patients with knee osteoarthritis. A controlled, randomized, double-blind, parallel-design multicentre study. Rheumatology (Oxford) 41: 1240-1248 [Abstract] [Full Text]  
• Chen, A. L., Desai, P., Adler, E. M., Di Cesare, P. E. (2002). Granulomatous Inflammation After Hylan G-F 20 Viscosupplementation of the Knee : A Report of Six Cases. JBJS 84: 1142-1147 [Abstract] [Full Text]  
• Petrella, R. J., DiSilvestro, M. D., Hildebrand, C. (2002). Effects of Hyaluronate Sodium on Pain and Physical Functioning in Osteoarthritis of the Knee: A Randomized, Double-blind, Placebo-Controlled Clinical Trial. Arch Intern Med 162: 292-298 [Abstract] [Full Text]  
• Bernardeau, C, Bucki, B, Liote, F (2001). Acute arthritis after intra-articular hyaluronate injection: onset of effusions without crystal. Ann Rheum Dis 60: 518-520 [Abstract] [Full Text]  
• Walker-Bone, K., Javaid, K., Arden, N., Cooper, C. (2000). Regular review: Medical management of osteoarthritis. BMJ 321: 936-940 [Full Text]  
• Watterson, J. R., Esdaile, J. M. (2000). Viscosupplementation: Therapeutic Mechanisms and Clinical Potential in Osteoarthritis of the Knee. J Am Acad Orthop Surg 8: 277-284 [Abstract] [Full Text]  
• Bliddal, H. (1999). Placement of intra-articular injections verified by mini air-arthrography. Ann Rheum Dis 58: 641-643 [Abstract] [Full Text]  
• (1999). Hyaluronan or hylans for knee osteoarthritis?. DTB 37: 71-72 [Abstract] [Full Text]  
• Clarke, A. K (1999). Effectiveness of rehabilitation in arthritis. Clin Rehabil 13: 51-62 [Abstract]  
• GEORGE, E (1998). Intra-articular hyaluronan treatment for osteoarthritis. Ann Rheum Dis 57: 637-640 [Full Text]