Background Crosslinked hylan is perceived to have longer efficacy than native hyaluronic acid in the treatment of osteoarthritis (OA).
Objectives To compare the efficacy of intra-articular injections of native sodium hyaluronate 1% (SH) and crosslinked hylan G-F 20 (hylan) in patients with tibiofemoral OA.
Methods This was a randomised, double-blind, controlled, non-inferiority study conducted from September 2007 through January 2010 in 64 sites in France. Selected patients were aged 40 to 80 years, with painful tibiofemoral OA (Kellgren-Lawrence radiological grade IIb to III) according to the American College of Rheumatology criteria and with WOMAC A pain on VAS of at least 40 mm. After an NSAID washout period, eligible patients were randomised to receive 1 intra-articular injection per week, for a total of 3 consecutive injections, of either SH 20 mg/2.0 ml (Ostenil®, TRB Chemedica AG, Germany) or hylan G-F 20 20 mg/2.0 ml (Synvisc®, Genzyme Biosurgery, USA). Efficacy parameters also included Lequesne index and SF-12 score, and were measured using the masked-observer technique at Days 45, 90 and 180. The main efficacy parameter was WOMAC A pain at Day 180. The PP population was used for the main analysis. The lower margin of non-inferiority for the 95% confidence interval was pre-specified at -8 mm. Data from this study were used to calculate responder rates according to the OMERACT-OARSI Set of Responder Criteria. 
Results 256 patients (mean age 64.4 years, 171 women) were evaluated as ITT (SH=132, hylan=124). Both groups’ baseline characteristics were homogeneous, except for a higher physical SF-12 in the test group (SH 34.0, hylan 32.2; p=0.028). All efficacy parameters decreased from baseline in both groups. In the PP population (226 patients, SH=119, hylan=107), the mean WOMAC A decrease at Day 80 was -28.9 mm (SD 20.8) and -27.8 mm (SD 22.9) for SH and hylan, respectively. The mean observed difference between groups was 1.04 mm (SEM 3.1), with a 95% confidence interval of [-5.0;7.1]. Therefore, the lower margin of the 95% confidence interval of the difference in mean WOMAC A was higher than the pre-specified bound for non-inferiority. Results were found to be similar in the ITT group. At baseline, 32.6% of SH patients and 22.1% of hylan patients had severe OA symptoms, as expressed with a Lequesne index of at least 14 points; at Day 180, only 5.1% of the patients in the SH group and 12.3% in the hylan group had a Lequesne index of 14 points or more. The responder rate at Day 180 was 75.7% in the SH group and 70.2% in the hylan group (p=0.38, chi-square test). Adverse reactions included burning sensation (1 occurrence), effusion (1), inflammatory reaction (3) in the SH group, and headache (3) and effusion (2) in the hylan group.
Conclusions Results of this multicentre clinical study in France demonstrated the non-inferiority of SH compared with hylan for the primary efficacy outcome. Both preparations reduced pain and improved functional activity in patients with painful tibiofemoral OA over 6 months.
Pham T, van der Heijde D, Altman RD et al. OMERACT-OARSI Initiative: Osteoarthritis Research Society International set of responder criteria for osteoarthritis clinical trials revisited. Osteoarthritis Cartilage 2004;12(5):389-99.
Disclosure of Interest R.-L. Dreiser Consultant for: Member of the Scientific Board for the study, B. Avouac Consultant for: Member of the Scientific Board for the study, T. Bardin Consultant for: National Study Co-ordinator