Open-label phase 3 study of diclofenac conjugated to hyaluronate (diclofenac etalhyaluronate: ONO-5704/SI-613) for treatment of osteoarthritis: 1-year follow-up

BackgroundWe evaluated the 1-year safety and efficacy of diclofenac etalhyaluronate (DF-HA), a diclofenac-conjugated hyaluronate, in patients with osteoarthritis (OA).MethodsIn this multi-centre, open-label, noncomparative phase 3 study in Japan, patients with a diagnosis of knee, shoulder, elbow, hip, or ankle OA received an intra-articular (IA) injection of DF-HA 30mg every 4weeks for 1year (13 times in total). The safety outcomes included treatment-emergent adverse events (TEAEs) and target joint structural changes by X-ray imaging tests. Efficacy outcomes included joint pain scores on an 11-point numerical rating scale. Concomitant use of analgesics was not restricted.ResultsOverall, 166 eligible patients were enrolled, comprising knee OA (n=126) and other OA (n=40). All TEAEs were experienced by 126/166 patients (75.9%). The incidence of treatment-related TEAEs was not associated with the treatment period. No significant worsening of joint status was observed in X-ray imaging tests at week 52 or at last assessment. The mean joint pain scores ( standard deviation) were 5.91.2, 4.9 +/- 1.9, and 3.1 +/- 2.3 at baseline, and weeks 2 and 52, respectively. Improvement of pain score was observed after the first injection and was maintained until week 52 regardless of knee OA or other joint OA.Conclusions Repeated IA injections of DF-HA every 4weeks for 1year were well tolerated with no clinically significant adverse events indicating they might lead to the long-term improvement of OA symptoms. DF-HA might be a useful treatment for patients with OA.Trial registration number JapicCTI-183855 (First registered date: 6th February 2018).

Automated summary

Repeated intra-articular injections of DF-HA every 4 weeks for 1 year were safe and effective in improving joint pain scores in patients with osteoarthritis, without clinically significant adverse events.