Safety and efficacy of retreatment with a bioengineered hyaluronate for painful osteoarthritis of the knee: results of the open-label Extension Study of the FLEXX Trial

Objective: To evaluate the safety of repeated intra-articular (IA) injections of Euflexxa® (1% sodium hyaluronate; IA--BioHA) for painful knee osteoarthritis (OA).

Design: Participants who completed the randomized, double-blind, 26-week FLEXX Trial comparing IA-BioHA to IA saline (IA-SA) for knee OA(1) received three weekly IA-BioHA injections in a 26-week Extension Study. Adverse events (AEs) were recorded and the effect of treatment on knee pain was measured immediately following a 50-foot walk test using a 100 mm visual analog scale (VAS). Responder rate, Medical Outcomes Study Short Form 36 scores, Patient's Global Assessment, and intake of rescue medication were also evaluated.

Results: The Extension Study included 433 subjects, 219 who received IA-BioHA and 214 who received IA-SA during the FLEXX Trial. Safety results from the Extension Study indicated that 43.4% (188/433) of subjects had AEs, of which 4.8% (21/433) were deemed treatment-related AEs. Two AEs in the Extension Study led to discontinuation, and no joint effusion was reported. Patients who continued with IA-BioHA in the Extension Study maintained their improvement from baseline, with an average reduction in pain in the VAS score of -3.5 mm. Patients initially treated with IA-SA in the FLEXX Trial also had a reduction in VAS score of -9.0 mm. Secondary efficacy variables also improved during the Extension Study.

Conclusions: Repeat injections of IA-BioHA were effective, safe, well tolerated, and not associated with an increase in AEs, such as synovial effusions. Additional symptom improvements were noted for subjects who received either IA-BioHA or IA-SA in the FLEXX Trial.

Clinical trial registration number: NCT00379236.