Abstract
BACKGROUND: To evaluate the efficacy and safety of intra-articular injection of diclofenac etalhyaluronate (DF-HA) in patients with osteoarthritis (OA) of the hip, ankle, shoulder, or elbow. METHODS: In this randomized, placebo-controlled, double-blind study in Japan, Japanese patients aged ≥20 years diagnosed with OA of the hip, ankle, shoulder, or elbow were randomly assigned 1:1 to DF-HA 30 mg or placebo (citric acid-sodium citrate buffered solution). Subjects received three injections of the study drug in each joint cavity every 4 weeks and were assessed for 12 weeks after the first injection. The primary endpoint was the mean change from baseline in a diary-based 11-point numerical rating scale (NRS) for pain over 12 weeks, analyzed for each joint. Treatment-emergent adverse events were recorded, and morphological changes in each joint were evaluated radiographically. RESULTS: The study drug (DF-HA vs placebo) was injected into 90, 60, 90, or 50 subjects with OA of the hip, ankle, shoulder, or elbow (46 vs 44, 30 vs 30, 45 vs 45, and 25 vs 25, respectively). The group differences in the mean change from baseline in the pain NRS over 12 weeks were - 0.81 (95% confidence interval: - 1.48 to - 0.13), - 0.07 (- 1.03 to 0.89), 0.15 (- 0.48 to 0.78), and 0.61 (- 0.41 to 1.62) for the hip, ankle, shoulder, and elbow joints, respectively, with statistically significant differences observed only in the hip joint. The change from baseline in the hip joint was greater with DF-HA than placebo at all time points from Weeks 1-12. No clinically significant adverse events or radiographic changes were observed. CONCLUSIONS: Intra-articularly administered DF-HA for hip OA produced a rapid response and was safe, with analgesia maintained for 12 weeks when administered every 4 weeks. TRIAL REGISTRATION: JapicCTI-173,678 (First registered date: 21 August 2017).