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Scientific Articles:
Seth S. Leopold, Winston J. Warme, Patrick D. Pettis, and Susan Shott
Increased Frequency of Acute Local Reaction to Intra-Articular Hylan GF-20 (Synvisc) in Patients Receiving More Than One Course of Treatment
J Bone Joint Surg Am 2002; 84: 1619-1623 [Abstract] [Full text] [PDF]
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[Read Letter to the Editor] A Randomized Comparison of Hylan G-F 20 and Sodium Hyaluronate
Duane C. Heald, Mark W Richardson, Leslie Droege   (30 June 2004)

A Randomized Comparison of Hylan G-F 20 and Sodium Hyaluronate 30 June 2004
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Duane C. Heald,
Orthopedic PA-C
USAF,
Mark W Richardson, Leslie Droege

Send letter to journal:
Re: A Randomized Comparison of Hylan G-F 20 and Sodium Hyaluronate

duane.heald{at}lackland.af.mil Duane C. Heald, et al.

To the Editor:

We read with interest “Increased Frequency of Acute Local Reaction to Intra-articular Hylan G-F 20 (Synvisc) in Patients Receiving More than One Course of Treatment” (2002;84-A:1619-23), by Leopold et al. and the subsequent letters the article stimulated. These focused on the increased frequency of pseudoseptic reactions to hylan G-F 20 (Synvisc). There have been four additional reports,(1-4) all associated with hylan G-F 20, since that publication, but there have been no published reports, to our knowledge that have investigated the naturally derived sodium hyaluronate products (Hyalgan or Supartz).

Pseudoseptic reactions are clinically distinct from inflammatory reactions, which can occur following any intra-articular injection(5). The preponderance of clinical reports (1-5) and preclinical data (6-9) is substantial, and considerable support for an immunological component to these reactions exists (5-10).

We conducted a prospective, single-blinded, comparative study evaluating 5 or 3 weekly injections of sodium hyaluronate (Hyalgan) or hylan G-F 20 (Synvisc), respectively. Our results further support the findings of Leopold et al., and suggest that these are hylan-specific reactions. Seventy-four patients with painful knee osteoarthritis were randomly assigned to receive sodium hyaluronate or hylan G-F 20 and completed at least one follow-up visit (6 weeks). The primary outcome measure was a 10 -cm visual analog scale assessment of pain following a 50-foot walk. Follow-ups were scheduled at 12, 18, 26 and 38 weeks following therapy. Sixty percent of the patients completing their Week 5 follow-up completed the Week 38 visit, and the majority of patients demonstrated significant improvement in pain (>20%) from baseline, with no significant difference between the treatments. While 2/38 (5.3%) patients in the hylan G-F 20 group (114 injections) developed pseudoseptic reactions, none of the patients in the sodium hyaluronate group (0/36 patients, 180 injections) reported such reactions.

Estimates in the literature of the frequency of pseudoseptic reactions have ranged from 1.8% to 27% of treated patients (5) with higher rates associated with repeat treatment courses. The impacts of subclinical reactions and additional sequelae (chronic granulomatous reactions) need to be considered when counseling patients considering repeat treatment with hylan G-F 20.

References 1. Tomas GJ, Lopez MP, Alegre J. Acute adverse reaction to hylan G-F 20: comment on the article by Martens. Arthritis Rheum. 2003;48:866. 2. Brown DJ, Wood EV, Hannah HM, Teanby D. A prospective comparative study of the safety and efficacy of sodium hyaluronate (HyalganŇ) and hylan G-F 20 (SynviscŇ) in a clinical practice [letter]. Arthritis Rheum. 2003 (In Press) 3. Noain E, Sancez-Villares J, Lasanta P, Gonzalez rteaga F. Acute local reaction to intra-articular infiltration with Synvisc (Hylan GF20). About two cases [Spanish]. An Sist Sanit Navar. 2003;26:283-5. 4. Shannon PD, Morton A. Reactions to hylan G-F 20 viscosupplementation are not a class effect. J Bone Joint Surg. 85-A:2050-1. 5. Goldberg VM, Coutts, RD. Pseudoseptic Reactions to Hylan viscosupplementation: Diagnosis and Management. Clin Orthop. 2004;419:130- 137. 6. Synvisc® PMA [Premarket Approval Application. Summary of Safety and Effectiveness Data]. Available at: ttp://www.fda.gov/cdrh/pdf/p940015.pdf. Accessed October 1, 2003. 7. Bucher W, Otto T, Hamburger MI. Differentiation of hyaluronate products by qualitative differences in their immunogenicity in rabbits: possible mechanism for product-specific severe adverse reactions? Arthritis Rheum. 2002;46:2543-4. 8. Schiavinato A, Finesso M, Abatangelo G. Comparison of the effects of intra-articular injections of hyaluronan and its chemically cross-linked derivative (hylan G-F 20) in normal rabbit knee joints. Clin Exp Rheumatol. 9. Sasaki M, Miyazaki Y, Takahashi T. Hylan G-F20 induces delayed foreign body inflammation in Guinea pigs and rabbits. Toxicol Pathol. 2003;31:321- 5. 10. Puttick MP, Wade JP, Chalmers A, Connell DG, Rangno KK. Acute local reactions after intraarticular hylan for osteoarthritis of the knee. J Rheumatol. 1995;22:1311-4.