Effect of Abaloparatide vs. Placebo on New Vertebral Fractures in Postmenopausal Women With Osteoporosis

Franklin Reeves, Mercer University College of Pharmacy

 

Osteoporosis has been identified as a major health burden, affecting 10 million Americans over the age of 50. In addition, an estimated 1.5 million fragility fractures are estimated to occur every year, costing $20 billion and leading to significant morbidity and mortality. To reduce financial burden and decreased quality of life, identification of new pharmacologic interventions has been deemed a priority.1

 

A meta-analysis encompassing 166 trials identified teriparatide, a recombinant parathyroid hormone (PTH), as the best treatment to reduce incidence of fractures. However, it was not indicated to be appreciably more effective than other available treatment options, such as denosumab or the bisphosphonates.1 As a result, the efficacy and safety of a new recombinant PTH mimic, abaloparatide, was assessed.

Title: Effect of Abaloparatide vs. Placebo on New Vertebral Fractures in Postmenopausal Women With Osteoporosis [2]

Design International, randomized, placebo and active-controlled trial; N= 2463
Objective To determine the efficacy and safety of abaloparatide vs. placebo for prevention of new vertebral fracture in postmenopausal women at risk of osteoporotic fracture
Study Groups Abaloparatide (n= 824); placebo (n= 821); teriparatide (n= 818)
Methods Anteroposterior and lateral radiographs of the lumbar and thoracic spine were obtained at baseline and at the end of treatment. Radiologists graded each woman’s vertebrae according to a decrease in height of 20% to 25% as mild, 26% to 40% as moderate, and more than 40% as severe.   A second radiologist reviewed radiographs in which an incident fracture had been identified to confirm the reading; if necessary, a third radiologist adjudicated the incident fracture. All treatments were blinded from adjudicators.
Duration March 2011 to October 2014
Primary Outcome Measure Percentage of participants with one or more incidents of new morphometric vertebral fracture
Baseline Characteristics
  Abaloparatide Placebo Teriparatide
Mean age (years) ± SD* 68.9 ± 6.5 68.7 ± 6.5 68.8 ± 6.6
Mean time since menopause (years) ± SD* 20.6 ± 8.3 19.9 ± 8.1 20.4 ± 8.2
Mean weight (kg) ± SD* 61.1 ± 10.0 61.2 ± 10.2 61.2 ± 10.3
Mean BMIa ± SD* 25.0 ± 3.5 25.1 ± 3.6 25.2 ± 3.6

a Body mass index (BMI): weight in kilograms divided by height in meters squared.

*Standard deviation (SD)

Results
Treatment Fracture occurrence (%) Relative risk (95% confidence interval) P-value
Abaloparatide 0.58 0.14 (0.05 to 0.39) <0.001
Teriparatide 0.84 0.20 (0.08 to 0.47) <0.001
Placebo 4.22
Adverse Events Common Adverse Events: orthostatic hypotension (17.1%), hypercalciuria (11.3%), dizziness (10%), arthralgia (8.6%), hypertension (7.2%)
Serious Adverse Events: neoplasms (2.4%), hypercalcemia (2.4%)
Percentage that Discontinued due to Adverse Events: Abaloparatide (9.9%), teriparatide (6.8%), placebo (6.1%)
Study Author Conclusions Among postmenopausal women with osteoporosis, the use of subcutaneous abaloparatide reduced the risk of new vertebral and non-vertebral fractures over 18 months. Further research is needed to understand the risks and benefits of abaloparatide treatment and the efficacy of abaloparatide vs. other osteoporosis treatments.

 

While abaloparatide was able to effectively reduce the incidence of vertebral fractures in post-menapausal women, the rate of adverse events associated with the drug was quite high. An alarming 17% of women experienced orthostatic hypertension during the 18-month study period, with a discontinuation rate of 10%. With this in mind, further evaluation should be performed on the drug’s potential to contribute to falls and risk of fracture in this population. In addition, a clinical risk to benefit ratio should be determined, along with side-by-side comparative trials against the gold standard bisphosphonates, to determine the utility of abaloparatide in prevention of fractures. With average monthly price data stating teriparatide at greater than $1,500 for a month supply opposed to bisphosphonates being as low as $40, significant differences will likely need to be shown in fracture reduction to support use of these new treatment options.3

 

 

References

  1. Murad MH, Drake MT, Mullan RJ, et al. Clinical review. Comparative effectiveness of drug treatments to prevent fragility fractures: a systematic review and network meta-analysis. J Clin Endocrinol Metab. 2012;97(6):1871-80.

 

  1. Miller PD, Hattersley G, Riis BJ, et al. Effect of Abaloparatide vs Placebo on New Vertebral Fractures in Postmenopausal Women With Osteoporosis: A Randomized Clinical Trial. JAMA. 2016;316(7):722-33.

 

  1. Consumer Reports. http://www.rheumatology.org/Portals/0/Files/Osteoporosis%20prevention.pdf. Accessed August 25, 2016.

 

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