Researchers found no statistically significant differences in pain or functional outcomes between Hyruan ONE, hylan G-F 20, and saline in a randomized trial of 276 patients with symptomatic knee osteoarthritis.
The single-center, double-blind, randomized, placebo-controlled trial was conducted at Thammasat University Hospital in Thailand and included patients with primary symptomatic knee osteoarthritis who had not responded to at least 3 months of conservative treatment.
Patients were randomly assigned in equal numbers to receive a single intra-articular injection of Hyruan ONE, an ultra-high-molecular-weight cross-linked hyaluronic acid formulation; hylan G-F 20; or saline. Hyruan ONE was administered in a 3-mL injection, whereas hylan G-F 20 and saline were administered in 6-mL injections.
Patients wore eye masks during administration to conceal differences in the injected materials, and patients and outcome evaluators were blinded to treatment assignment.
The primary outcomes were pain at rest and during motion, measured repeatedly on a 100-mm visual analog scale through 24 weeks. Secondary outcomes included the modified Western Ontario and McMaster Universities Osteoarthritis Index, Short Form-36, Lequesne index, Timed Up and Go test, and active knee flexion.
Researchers used linear mixed-effects models that accounted for repeated measurements and included treatment group, time, the interaction between treatment and time, baseline pain, and demographic covariates.
Pain scores decreased from baseline in all 3 groups, but the researchers found no statistically significant between-group differences in pain at rest or during motion over 24 weeks.
No statistically significant between-group differences were observed in modified Western Ontario and McMaster Universities Osteoarthritis Index scores, Short Form-36 scores, Lequesne index scores, Timed Up and Go results, or active knee flexion. Most patient-reported outcomes and knee-flexion measures improved from baseline, whereas Timed Up and Go performance did not show statistically significant improvement over time.
The researchers reported rescue corticosteroid use in 17% of patients assigned to Hyruan ONE, 21% assigned to hylan G-F 20, and 25% assigned to saline, with no statistically significant difference among the groups.
Patients who reported inadequate improvement or dissatisfaction could discontinue the study and receive a 40-mg intra-articular triamcinolone injection. Their subsequent data were excluded from further analyses.
Eight patients were lost to follow-up, and 56 discontinued because of inadequate symptom relief. At 24 weeks, 74 patients in the Hyruan ONE group, 71 in the hylan G-F 20 group, and 67 in the saline group had completed all assessments.
The researchers said the improvement observed in the saline group was consistent with previous evidence of responses to intra-articular saline injections. They cited possible effects related to dilution of inflammatory mediators and the psychological impact of the injection procedure.
They also said the cost-effectiveness of the hyaluronic acid formulations relative to saline remained uncertain and warranted formal economic evaluation.
The researchers acknowledged several limitations, including the 24-week follow-up period and final completion rates of approximately 73% to 80%. Although the study included patients across all Kellgren-Lawrence grades, approximately 90% had grade II or III disease, and patients with mechanical-axis deviation of at least 10 degrees were excluded.
Adverse events were not systematically assessed. The researchers reported that no significant adverse events were identified during follow-up knee examinations, but they said further research was warranted to evaluate the long-term efficacy and safety of Hyruan ONE.
“In conclusion, intra-articular injections of ultra-high MW and HMW cross-linked HAs did not demonstrate superior efficacy in pain reduction or functional improvement compared with saline in patients with symptomatic knee OA,” wrote study author Supakit Kanitnate, MD, of the Department of Orthopedics, Faculty of Medicine, Thammasat University, Pathum Thani, Thailand, and colleagues.
Disclosures: The study was funded by Thammasat University and supported in part by the Thammasat Postdoctoral Fellowship Program. LG Life Sciences Thailand supplied the hyaluronic acid products used in the study. Conflict-of-interest forms were available with the published article. The researchers also acknowledged using Google Gemini to assist with manuscript clarity and language.
Source: JBJS Open Access
