An ICER analysis and expert commentary on anabolics’ benefits and costs offer some opposing views, and some consensus.
For 2 anabolic agents used to treat patients with osteoporosis, the incremental costs of additional quality adjusted life-years (QALYs) gained would exceed the commonly cited willingness-to-pay threshold, according to a cost-effectiveness analysis recently conducted by the Institute for Clinical and Economic Review (ICER).
ICER, a nonprofit organization that evaluates evidence on the value of medical tests, treatments, and delivery system innovations, published its final evidence report on the cost-effectiveness of the agents in mid-July after a public meeting of the California Technology Assessment Forum, which deliberated key questions raised by ICER’s initial report.
Rheumatologist Andrew Laster, MD, an expert on osteoporosis and a member of the Medical Policy Committee at United Rheumatology, the country’s largest organization of independent community-based rheumatologists, expressed concerns to Rheumatology Network about the implications of the ICER osteoporosis report.
Dire fracture consequences
Osteoporosis affects about 10 million Americans, and another 44 million have low bone density. According to the American Society for Bone and Mineral Research (ASBMR), 1 in 2 women and up to 1 in 4 men will break a bone in their lifetime because of osteoporosis, often with serious consequences. One in 4 patients older than 50 years with a hip fracture will die within a year of the fracture, ASBMR reports, and 1 in 5 will die within the following year. In addition, at least 40% will lose their independence and require long-term extended care.
Fractures also come with a high cost to the health care system. An estimated 2 million osteoporotic fractures occur each year, resulting in $19 billion in related costs. As the population of older Americans grows, these figures are predicted to increase to about 3 million fractures and $25 billion in annual costs by 2025.
Two anabolic therapies are currently approved by the FDA for osteoporosis.
Teriparatide (Forteo, Eli Lilly and Co.) was the first FDA-approved osteoporosis drug that works primarily by increasing bone formation, rather than decreasing the breakdown of bone, as do antiresorptive agents. Teriparatide requires a daily injection from a prefilled pen injector, which must be kept refrigerated.
Abaloparatide (Tymlos, Radius Health, Inc.), just recently approved in April 2017, acts through a similar mechanism and also requires a daily injection but does not require refrigeration after the first dose.
Both are indicated for the treatment of postmenopausal women with osteoporosis who are at high risk for fracture.
The ICER report originally intended to include romosozumab (Amgen, Inc. and UCB, Inc.) until Amgen announced that FDA approval is not expected to occur in 2017.
ICER performed a network meta-analysis (NMA) to compare teriparatide and abaloparatide. In addition, based on feedback from multiple stakeholders, the NMA included zoledronic acid, a frequently used parenteral therapy for patients with osteoporosis who are unable to tolerate oral therapy. Zoledronic acid requires an annual visit for a 15-minute infusion.
The cost-effectiveness analysis used a simulation model to compare the anabolic drugs, each followed by treatment with zoledronic acid (because anabolic agents are used for only 1 or 2 years), versus treatment with zoledronic acid alone in a representative cohort of postmenopausal women who are at high risk for osteoporotic fractures.
The model tracked vertebral fractures (both morphometric and clinical), hip fractures, other nonvertebral fractures, and death. Model outputs included total costs, QALYs, life years for interventions and comparators, and incremental costs per additional QALY and life year gained. In addition to a base case analysis, ICER conducted sensitivity analyses using ranges of values for model inputs.
The NMA “demonstrates with high certainty that the 2 anabolic agents reduce vertebral fractures compared to no therapy,” ICER concluded. “However,” the report continued, “there is insufficient evidence to distinguish the anabolic agents from each other and from zoledronic acid for vertebral fractures.”
In the cost-effectiveness analysis, each anabolic agent was associated with a net price per pen ($1,866 per 28-dose pen for teriparatide, $1,186 per 30-dose pen for abaloparatide) based on wholesale acquisition cost plus applied discounts (38% known discount for teriparatide, 27% discount for abaloparatide representing the average industry-wide discount). Other nondrug costs, such as fracture treatment costs and administration costs for zoledronic acid, were derived from published literature.
Although the analysis did find that anabolic therapies resulted in increased QALYs and life years compared with zoledronic acid, incremental costs versus those of zoledronic acid ranged from a low of $22,061 for abaloparatide to $43,440 for teriparatide. These base case incremental cost-effectiveness ratios compared with zoledronic acid far exceeded the frequently cited cost-effectiveness willingness-to-pay threshold of $150,000 per QALY.
In the sensitivity analysis, none of the modeled parameters’ range values resulted in incremental cost-effectiveness ratios less than $150,000 per QALY gained. ICER concluded that “fracture risks would need to be approximately 118% higher for abaloparatide to approach the $150,000 QALY threshold,” and continued, “teriparatide did not approach commonly cited cost effectiveness thresholds until a >1000% increased risk of fracture was applied.”
Implications for patients and policy
The anabolic agents studied may offer effective treatment options for osteoporosis, but cost is certainly an important consideration for both patients and payers. United Rheumatology commended ICER’s focus on the rising costs of drugs and the need to make treatment options more affordable for patients. However, Dr Laster stated several concerns.
He said he recognizes that ICER faced a challenge with this study in trying to properly identify the patient population that would best benefit from using an anabolic drug. He estimates that no more than 5% of patients who are treated for osteoporosis or low bone mass truly fall into this category. However, the enrollment criteria for the trials examined in the NMA were not based only on patients at very high risk for fracture, because for ethical reasons these patients cannot be placed in a blinded placebo group.
By looking at a wider population, the ICER study may not have been able to properly see the true benefit of anabolic medications, Dr Laster fears, and that could have the unintentional effect of limiting access to effective drugs for at-risk patients who could clearly benefit.
Dr Laster also expressed concern that insurance companies could use ICER’s conclusions about high costs to implement step therapy policies, a type of prior authorization that requires patients to try less expensive drugs before a more expensive drug will be covered.
Step therapy could be particularly problematic in this situation, he noted, because taking the less expensive antiresorptive agents could reduce the beneficial bone building effects of anabolic treatments. A policy put in place to minimize cost could actually end up minimizing the benefit of the anabolic drugs themselves.
Dr Laster and United Rheumatology say they appreciate that the costs of anabolic treatments are indeed high, but they argue that there is still a potential benefit for specific patients. They recommend that ICER work to develop criteria that might allow the highest-risk patients to go straight to the anabolic treatments. The criteria could include multiple fractures of a high grade or a very low T-score.
They also recommend re-examination of more recent data that may show anabolic drugs are superior to antiresorptive agents, though these studies have not yet gone through peer review.
Institute for Clinical and Economic Review (ICER). “Anabolic Therapies for Osteoporosis in Postmenopausal Women: Effectiveness and Value.” Final Evidence Report published July 17, 2017.