Abaloparatide in patients with mild or moderate renal impairment: results from the ACTIVE phase 3 trial

Curr Med Res Opin. 2019 Dec;35(12):2097-2102. doi: 10.1080/03007995.2019.1656955. Epub 2019 Sep 11.

Abstract

Objective: To evaluate, post hoc, the efficacy and safety of abaloparatide by degree of renal impairment.Methods: ACTIVE was a phase 3, 18-month, randomized, double-blind, active-comparator, placebo-controlled study of postmenopausal women with osteoporosis who received subcutaneous abaloparatide 80 µg, placebo, or open-label teriparatide 20 µg daily. Patients with serum creatinine >2.0 mg/dL or 1.5-2.0 mg/dL with an estimated glomerular filtration rate (eGFR) <37 mL/min, calculated by Cockcroft-Gault formula, were excluded.Results: At baseline, 660 patients had eGFR ≥90 mL/min, 1276 had 60 to ˂90 mL/min, and 527 had <60 mL/min. Older age and lower T-scores were associated with greater renal impairment. Among renal-function subgroups, there were no meaningful changes in bone mineral density, fracture risk reduction, or overall incidence of treatment-emergent adverse events in the active-treatment arms. Anemia, nausea, hypercalcemia, and upper-respiratory-tract infection tended to be more frequent with increasing renal impairment. Hypercalcemia measured by albumin-adjusted serum calcium occurred significantly less frequently with abaloparatide than teriparatide in patients with eGFR <60 mL/min (3.6% versus 10.9%; p = .008) and in the overall ACTIVE safety population (3.4% versus 6.4%; p = .006). Computed tomography scans in 376 patients revealed no evidence of increased renal calcification.Conclusion: Increased exposure to abaloparatide and teriparatide in patients with renal impairment led to no meaningful differences in efficacy or safety. These results support the use of abaloparatide without dosage adjustment in patients with renal impairment, provided those with severe renal impairments are monitored for adverse events.

Keywords: Osteoporosis; abaloparatide; bone density conservation agents; bone regeneration; postmenopausal; renal insufficiency.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Bone Density Conservation Agents / administration & dosage
  • Bone Density Conservation Agents / adverse effects
  • Bone Density Conservation Agents / therapeutic use
  • Double-Blind Method
  • Drug Monitoring
  • Female
  • Fractures, Bone / epidemiology
  • Glomerular Filtration Rate / drug effects*
  • Humans
  • Kidney / diagnostic imaging*
  • Middle Aged
  • Osteoporosis, Postmenopausal* / complications
  • Osteoporosis, Postmenopausal* / drug therapy
  • Parathyroid Hormone-Related Protein* / administration & dosage
  • Parathyroid Hormone-Related Protein* / adverse effects
  • Renal Insufficiency* / complications
  • Renal Insufficiency* / diagnosis
  • Teriparatide / administration & dosage
  • Teriparatide / adverse effects
  • Tomography, X-Ray Computed / methods
  • Treatment Outcome

Substances

  • Bone Density Conservation Agents
  • Parathyroid Hormone-Related Protein
  • Teriparatide
  • abaloparatide