A Double-Blind, Randomized, Saline-Controlled Study of the Efficacy and Safety of EUFLEXXA for Treatment of Painful Osteoarthritis of the Knee, With an Open-Label Safety Extension (The FLEXX Trial)

Semin Arthritis Rheum. 2009 Aug;39(1):1-9. doi: 10.1016/j.semarthrit.2009.04.001. Epub 2009 Jun 17.

Abstract

Objective: To report the FLEXX trial, the first well-controlled study assessing the safety and efficacy of Euflexxa (1% sodium hyaluronate; IA-BioHA) therapy for knee osteoarthritis (OA) at 26 weeks.

Methods: This was a randomized, double-blind, multicenter, saline-controlled study. Subjects with chronic knee OA were randomized to 3 weekly intra-articular (IA) injections of either buffered saline (IA-SA) or IA-BioHA (20 mg/2 ml). The primary efficacy outcome was subject recorded difference in least-squares means between IA-BioHA and IA-SA in subjects' change from baseline to week 26 following a 50-foot walk test, measured via 100-mm visual analog scale (VAS). Secondary outcome measures included Osteoarthritis Research Society International responder index, Western Ontario McMaster University Osteoarthritis Index VA 3.1 subscales, patient global assessment, rescue medication, and health-related quality of life (HRQoL) by the SF-36. Safety was assessed by monitoring and reporting vital signs, physical examination of the target knee following injection, adverse events, and concomitant medications.

Results: Five hundred eighty-eight subjects were randomized to either IA-BioHA (n = 293) or IA-SA (n = 295), with an 88% 26 week completion rate. No statistical differences were noted between the treatment groups at baseline. In the IA-BioHA group, mean VAS scores decreased by 25.7 mm, compared with 18.5 mm in the IA-SA group. This corresponded to a median reduction of 53% from baseline for IA-BioHA and a 38% reduction for IA-SA. The difference in least-squares means was -6.6 mm (P = 0.002). Secondary outcome measures were consistent with significant improvement in Osteoarthritis Research Society International responder index, HRQoL, and function. Both IA-SA and IA-BioHA injections were well tolerated, with a low incidence of adverse events that were equally distributed between groups. Injection-site reactions were reported by 1 (<1%) subject in the IA-SA group and 2 (1%) in the IA-BioHA group.

Conclusions: IA-BioHA therapy resulted in significant OA knee pain relief at 26 weeks compared with IA-SA. Subjects treated with IA-BioHA also experienced significant improvements in joint function, treatment satisfaction, and HRQoL.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / administration & dosage
  • Adjuvants, Immunologic / adverse effects*
  • Adjuvants, Immunologic / therapeutic use*
  • Aged
  • Arthralgia / etiology
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Female
  • Humans
  • Hyaluronic Acid / administration & dosage
  • Hyaluronic Acid / adverse effects*
  • Hyaluronic Acid / therapeutic use*
  • Injections, Intra-Articular
  • Male
  • Middle Aged
  • Molecular Weight
  • Osteoarthritis, Knee / complications
  • Osteoarthritis, Knee / drug therapy*
  • Osteoarthritis, Knee / physiopathology
  • Outcome Assessment, Health Care
  • Pain Measurement
  • Quality of Life
  • Treatment Outcome
  • United States
  • Walking / physiology

Substances

  • Adjuvants, Immunologic
  • Hyaluronic Acid