Long-term safety and effectiveness of denosumab in Japanese patients with osteoporosis: 3-year post-marketing surveillance study

Abstract

Denosumab is a humanized IgG2 monoclonal antibody that was approved for the treatment of osteoporosis in Japan in 2013. This study aimed to investigate the long-term safety and effectiveness of denosumab in Japanese patients with osteoporosis in daily clinical practice. This 3-year, prospective, observational, post-marketing study included patients who initiated treatment with denosumab (60mg/6months) for osteoporosis. Data were assessed at baseline, 3, 6, 12, 24 and 36months. Key endpoints were adverse events (AEs), adverse drug reactions (ADRs), occurrence of osteoporotic fractures, bone mineral density (BMD), and bone turnover markers. Multivariate analyses were conducted to identify predictors of hypocalcaemia and percent change in BMD. Overall, 3534 patients were assessed (mean 75.7years; 89.8% women). In total, 298 patients (8.4%) developed ADRs; the most common was hypocalcaemia (3.9%). Hypocalcaemia risk was significantly increased in patients with creatinine clearance < 30mL/min, no prior use of bisphosphonates, prior use of calcium and vitamin D preparations, baseline serum calcium < 8.5mg/dL, and no concomitant use of calcium or vitamin D preparations. Six patients had adjudicated osteonecrosis of the jaw. Lumbar spine BMD increased significantly from baseline (mean percent change: 11.4% at 36months). All bone turnover markers decreased significantly from baseline. Over 3years, 3.3% of patients developed a new osteoporotic fracture. This study confirmed the long-term safety and effectiveness of denosumab in Japanese patients with osteoporosis in daily clinical practice. No new safety signals were identified.