Background/Purpose:

Abaloparatide (ABL) is an anabolic PTHrP analog approved to treat postmenopausal women with osteoporosis at high risk of fracture. In the ACTIVE Phase 3 study of postmenopausal osteoporotic women, 18 months of ABL significantly increased bone mineral density (BMD) and reduced the risk of vertebral, nonvertebral, clinical, and major osteoporotic fractures versus placebo (PBO) irrespective of baseline risk factors. In ACTIVExtend, women assigned to receive ABL or PBO in ACTIVE were offered enrollment in an extension study during which both groups received open-label alendronate (ALN) 70 mg weekly for 24 months. In this analysis, we assess whether fracture risk reduction and BMD gains were consistent across multiple subgroups categorized by baseline risk.

Methods:

A total of 1,139 patients (558, ABL/ALN and 581, PBO/ALN) were enrolled in ACTIVExtend (18 months of ABL or PBO followed by 1 month for re-consent, followed by 24 months of ALN treatment for a total of 43 months). Risk factor subgroups were prospectively defined by BMD T-score of the lumbar spine, total hip, and femoral neck (≤ -2.5 vs > -2.5; ≤ -3.0 vs > -3.0); nonvertebral fracture history (yes/no); prevalent vertebral fracture at baseline of ACTIVE (yes/no); and age (< 65 vs 65 to < 75 vs ≥ 75 years) at baseline. Treatment effects in subgroups were assessed by forest plots and statistical tests for interactions using relative risk ratios for new vertebral fractures (Breslow-Day test), hazard ratios for nonvertebral fractures (Cox proportional hazards model), and least-squares mean differences in percent change for BMD (ANCOVA).

Results:

Patients in ACTIVExtend were well balanced for baseline characteristics including age, lumbar spine BMD, total hip BMD, femoral neck BMD, vertebral fracture, and prior nonvertebral fracture. The relative risk reductions for new vertebral, non-vertebral, clinical, and major osteoporotic fractures were greater in the ABL/ALN group compared with the PBO/ALN group for all subgroups analyzed. There was no evidence of meaningful interaction between treatment assignment and any baseline risk variable. Additionally, BMD gains at 43 months for total hip, femoral neck, and lumbar spine were greater in the ABL/ALN group versus the PBO/ALN group among all subgroups analyzed without any meaningful interaction between treatment assignment and any baseline risk variable.

Conclusion:

These results suggest that the improved efficacy of 18 months of ABL followed by 24 months of ALN versus 18 months of PBO followed by 24 months of ALN is unaffected by baseline risk. Fracture risk reductions and BMD increases were consistent among all prespecified patient risk subgroups.

« Back to 2018 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/fracture-and-bone-mineral-density-response-by-baseline-risk-in-patients-treated-with-abaloparatide-followed-by-alendronate/