LAUSR

Objective To assess the efficacy and safety of 18 months of subcutaneous abaloparatide (ABL‐SC) or placebo (PBO) followed by 6 months of alendronate (ALN) (preplanned interim analysis). Patients and Methods ACTIVExtend, an extension of ACTIVE, enrolled patients who completed 18 months of ABL‐SC or PBO in ACTIVE to receive up to 24 additional months of open‐label ALN; there was 1 month between the studies to re‐consent patients. Results Of 1243 eligible ACTIVE patients, 1139 (92%) were enrolled in ACTIVExtend beginning November 20, 2012. These results are from a prespecified 6‐month interim analysis (cutoff date, June 2, 2015); the study is ongoing. Findings indicated percentages of patients with new morphometric vertebral fractures: PBO/ALN, 4.4% vs ABL‐SC/ALN, 0.55%; relative risk reduction, 87% (relative risk, 0.13; 95% CI, 0.04–0.41; P<.001). Kaplan‐Meier estimated rates of nonvertebral fractures were PBO/ALN, 5.6% vs ABL‐SC/ALN, 2.7%; risk reduction, 52% (hazard ratio [HR], 0.48; 95% CI, 0.26–0.89; log‐rank P=.02). There was also a 58% risk reduction of major osteoporotic fractures (HR, 0.42; 95% CI, 0.21–0.85; log‐rank P=.01) and a 45% risk reduction of clinical fractures (HR, 0.55; 95% CI, 0.33–0.92; log‐rank P=.02) in the ABL‐SC/ALN group vs the PBO/ALN group. At 25 months, bone mineral density percentage change from ACTIVE baseline for ABL‐SC/ALN vs PBO/ALN was as follows: lumbar spine, 12.8%; total hip, 5.5%; femoral neck, 4.5% vs 3.5%, 1.4%, 0.5%, respectively (group differences at all sites P<.001). Conclusion Use of ABL‐SC for 18 months followed by ALN for 6 months improved bone mineral density and reduced fracture risk throughout the skeleton and may be an effective treatment option for postmenopausal women with osteoporosis. Trial Registration clinicaltrials.gov Identifier: NCT01657162.