WHAT IS THE MOST COST-EFFECTIVE STRATEGY FOR TREATING CHRONIC MYELOID LEUKEMIA AFTER IMATINIB LOSES PATENT EXCLUSIVITY IN THE UNITED STATES?

Purpose: To analyze the cost-effectiveness of treating all newly diagnosed chronic-phase chronic myeloid leukemia (CML) patients with imatinib as first-line therapy using a step therapy, compared to physician's choice between imatinib or the second-generation tyrosine kinase inhibitors (TKIs) dasatinib or nilotinib. Currently, each TKI is oral, patent-protected and commands one-third of treatment. Imatinib will lose patent exclusivity and face generic competition in January, 2015. Within one year of generic entry, imatinib's price is expected to drop 60-90%.

Method: A Markov model simulating "step therapy" compared to "physician choice" in treating incident chronic-phase CML in 2015 through 5 years. The model assumes the commercial payer perspective. In both approaches, if initial treatment fails, patients are switched to a second-generation TKI. Patients are assumed to switch if they fail to meet efficacy endpoints: complete cytogenetic response (CCyR) or major molecular response (MMR). The model assumes stabilized prices of second-generation TKIs, but adjusts the price of imatinib to be 100% of the branded price for first 6-months, 60-80% for the second 6-months and 10-30% thereafter.

For each drug, tolerance, efficacy and the probabilities of treatment choice, switching and failure were drawn from published clinical trials. Quality-adjusted life years (QALYs) were based on US-societal health utilities (Szabo et al. 2010). Direct medical costs per patient were drawn from Marketscan (2001-2007) and include annual drug prices, imatinib ($76,800), dasatinib and nilotinib ($102,000). Additional costs included patient monitoring and allogeneic transplantation. Costs and QALYs were discounted at 3% ($US; 2013). Univariate and multivariate sensitivity analyses tested parameters with the greatest impact on results. Findings were interpreted from a willingness-to-pay of $100,000/QALY.

Results: Step therapy costs less and offers CML patients clinically-equivalent utility ($147,091; 3.250 QALYs) compared to physician choice ($172,867; 3.361 QALYs). Step therapy is estimated to have an incremental cost-effectiveness ratio of $227,136/QALY.

The results are robust to changes based on univariate analyses of the most sensitive parameters (imatinib associated probability of CCyR/MMR and price drops and the health utility of CCyR/MMR failure). Multivariate probabilistic sensitivity analyses using 10,000 Monte Carlo simulations suggest that step therapy is cost-effective over physician choice in 73.3% of simulations (Fig.1).

Conclusion: When imatinib loses patient protection in 2015, it will be the cost-effective initial treatment strategy for incident CML compared to dasatinib and nilotinib.