Effect of abaloparatide on vertebral,nonvertebral, major osteoporotic and clinical fractures in a subset of postmenopausal women at increased risk of fracture by FRAX probability

Summary We evaluated the efficacy of abaloparatide in women who were at increased risk for fracture, based on CHMP recommended risk thresholds, at the Abaloparatide Comparator Trial In Vertebral Endpoints (ACTIVE) study baseline. Among patients at high risk based on FRAX probabilities, 18 months of abaloparatide significantly decreased risk for all fracture endpoints compared with placebo. Purpose Abaloparatide, a novel anabolic agent for the treatment of postmenopausal osteoporosis, significantly reduced the risk of vertebral and nonvertebral fractures in the ACTIVE study compared with placebo. In this post hoc analysis, we evaluated abaloparatide’s efficacy in a subset of women in the study at an increased risk of fracture at baseline, based on the Committee for Medicinal Products for Human Use (CHMP) recommended risk thresholds for inclusion in clinical trials. Methods Women with a baseline 10-year risk of major osteoporotic fracture ≥ 10% or hip fracture ≥ 5%, assessed using the FRAX® tool (including femoral neck bone mineral density), were included in the analysis. The proportion with one or more events of new morphometric vertebral fractures was calculated. Event rates for nonvertebral, major osteoporotic, and all clinical fractures were estimated using Kaplan-Meier analysis. Results Following 18 months of treatment, abaloparatide significantly reduced incident vertebral fractures compared with placebo (relative risk reduction = 91%; 0.5% versus 5.6%; p < 0.001). Abaloparatide treatment was also associated with significantly fewer nonvertebral, major osteoporotic, and clinical fractures compared with placebo: 2.7% versus 5.8%, p = 0.036; 1.3% versus 6.0%, p < 0.001; and 3.5% versus 8.2%, p = 0.006, respectively. The effect of abaloparatide on major osteoporotic fractures (78% reduction) was significantly greater than that seen with teriparatide (23% reduction, p = 0.007). Conclusion In a subset of postmenopausal women at increased risk of fracture as judged by CHMP guidance, abaloparatide significantly decreased the risk of all fracture endpoints compared with placebo.