Economic evaluation and budget impact analysis of denosumab for the treatment of postmenopausal osteoporosis in Malaysia

Abstract

Denosumab has a promising efficacy and safety profile but is still underused in public hospitals. Alendronate remains the most commonly used drug for the treatment of osteoporosis. The main reason for this is likely the higher drug acquisition cost of denosumab, although denosumab is associated with better treatment adherence and reduces fracture risk more effectively than alendronate. Therefore, it is unknown whether denosumab offers better value for money and whether it is affordable from a healthcare provider perspective for the treatment of postmenopausal osteoporosis in Malaysia. The general objective of this thesis was to assess the cost-effectiveness and budget impact of denosumab compared with alendronate for the treatment of postmenopausal osteoporosis from the perspective of the Malaysian Ministry of Health (MOH) healthcare provider. Health-related quality of life (HRQoL) instruments in patients with osteoporosis were systematically appraised. Measurement properties such as validity, reliability, and responsiveness of the 41-item Quality of Life Questionnaire of the European Foundation for Osteoporosis (QUALEFFO-41) were assessed. A wellvalidated Markov model was used to evaluate the cost-effectiveness of denosumab compared with alendronate over a 10-year time horizon and a 5-year budget impact. Parameters used in the model were based on Malaysian data when available; otherwise, they were taken from the published literature. The cost-effectiveness was expressed as incremental cost-effectiveness ratios (ICERs) in cost per quality-adjusted life-year (QALY) gained. The budget impact was estimated by comparing a current scenario (current treatment mix) with an alternative scenario (increased uptake of denosumab). Overall, the QUALEFFO-41 was rated as moderate quality evidence for sufficient content validity and moderate-to-high quality evidence for sufficient hypothesis testing for construct validity. The QUALEFFO-41 was classified as category B and may be a promising, reliable, and valid measure of patient-reported outcomes for measuring HRQoL in osteoporosis. Denosumab was found to be more cost-effective than alendronate, with ICERs ranging from MYR 16,955 per QALY at age 60 years to MYR 4,380 per QALY at age 80 years. As expected, denosumab was also more cost-effective than no treatment, with equivalent ICERs ranging from MYR 23,223 per QALY to MYR 9,127 per QALY. One-way sensitivity analyses showed that the results were robust within all parameter variations, with the most sensitive parameter being the annual cost of denosumab. In addition, probabilistic sensitivity analysis showed that denosumab is likely to be cost-effective at age 60 and older with a probability of 72.8- 92.7%, suggesting that denosumab should be initiated in postmenopausal osteoporotic women older than 60 years. Finally, the incremental budget impact is expected to increase with the increasing uptake of denosumab, from MYR 0.26 million in the first year to MYR 3.25 million in the fifth year. Converted to cost per-member-per-month (PMPM), they were less than MYR 0.01 across all five years of treatment. Considering the clinical and economic impact, increasing uptake of denosumab is likely a rational and affordable approach. Therefore, from the perspective of the Malaysian MOH healthcare provider, optimizing the use of denosumab could be a potentially costeffective and affordable strategy to reduce the enormous economic burden of the disease in Malaysia