Cost-effectiveness of Tyrosine Kinase Inhibitor Treatment Strategies for Chronic Myeloid Leukemia in Chronic Phase After Generic Entry of Imatinib in the United States

Background: We analyzed the cost-effectiveness of treating incident chronic myeloid leukemia in chronic phase (CML-CP) with generic imatinib when it becomes available in United States in 2016. In the year following generic entry, imatinib’s price is expected to drop 70% to 90%. We hypothesized that initiating treatment with generic imatinib in these patients and then switching to the other tyrosine-kinase inhibitors (TKIs), dasatinib or nilotinib, because of intolerance or lack of effectiveness (“imatinib-first”) would be cost-effective compared with the current standard of care: “physicians’ choice” of initiating treatment with any one of the three TKIs. Methods: We constructed Markov models to compare the five-year cost-effectiveness of imatinib-first vs physician’s choice from a US commercial payer perspective, assuming 3% annual discounting ($US 2013). The models’ clinical endpoint was five-year overall survival taken from a systematic review of clinical trial results. Per-person spending on incident CML-CP treatment overall care components was estimated using Truven’s MarketScan claims data. The main outcome of the models was cost per quality-adjusted life-year (QALY). We interpreted outcomes based on a willingness-to-pay threshold of $100 000/QALY. A panel of European LeukemiaNet experts oversaw the study’s conduct. Results: Both strategies met the threshold. Imatinib-first ($277 401, 3.87 QALYs) offered patients a 0.10 decrement in QALYs at a savings of $88 343 over five years to payers compared with physician’s choice ($365 744, 3.97 QALYs). The imatinib-first incremental cost-effectiveness ratio was approximately $883 730/QALY. The results were robust to multiple sensitivity analyses. Conclusion: When imatinib loses patent protection and its price declines, its use will be the cost-effective initial treatment strategy for CML-CP.

[1]  R. Larson,et al.  Changing the cost of care for chronic myeloid leukemia: the availability of generic imatinib in the USA and the EU , 2015, Annals of Hematology.

[2]  M. D. de Lemos,et al.  Clinical efficacy of generic imatinib , 2015, Journal of oncology pharmacy practice : official publication of the International Society of Oncology Pharmacy Practitioners.

[3]  M. Baccarani,et al.  Final Study Results of the Phase 3 Dasatinib Versus Imatinib in Newly Diagnosed Chronic Myeloid Leukemia in Chronic Phase (CML-CP) Trial (DASISION, CA180-056) , 2014 .

[4]  J. Apperley,et al.  Chronic myeloid leukemia-transplantation in the tyrosine kinase era. , 2014, Hematology/oncology clinics of North America.

[5]  S. Pearson,et al.  The ethics of 'fail first': guidelines and practical scenarios for step therapy coverage policies. , 2014, Health affairs.

[6]  H. Kantarjian,et al.  High cancer drug prices in the United States: reasons and proposed solutions. , 2014, Journal of oncology practice.

[7]  T. Brümmendorf,et al.  Long-term outcome with dasatinib after imatinib failure in chronic-phase chronic myeloid leukemia: follow-up of a phase 3 study. , 2014, Blood.

[8]  E. Berndt,et al.  Specialty Drug Prices and Utilization after Loss of U.S. Patent Exclusivity, 2001-2007 , 2014 .

[9]  R. Larson,et al.  Early molecular response predicts outcomes in patients with chronic myeloid leukemia in chronic phase treated with frontline nilotinib or imatinib. , 2014, Blood.

[10]  J. Cayuela,et al.  Loss of major molecular response as a trigger for restarting tyrosine kinase inhibitor therapy in patients with chronic-phase chronic myelogenous leukemia who have stopped imatinib after durable undetectable disease. , 2014, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[11]  R. Allen,et al.  Determining the cost of obesity and its common comorbidities from a commercial claims database , 2014, Clinical obesity.

[12]  Aaron N. Winn,et al.  Cost sharing and adherence to tyrosine kinase inhibitors for patients with chronic myeloid leukemia. , 2014, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[13]  S. Goldberg,et al.  Economic benefits of adequate molecular monitoring in patients with chronic myelogenous leukemia , 2014, Journal of medical economics.

[14]  M. Baccarani,et al.  Early response with dasatinib or imatinib in chronic myeloid leukemia: 3-year follow-up from a randomized phase 3 trial (DASISION). , 2014, Blood.

[15]  F. Mahon,et al.  Deep Molecular Response in Chronic Myeloid Leukemia: The New Goal of Therapy? , 2013, Clinical Cancer Research.

[16]  Francisco Cervantes,et al.  European LeukemiaNet recommendations for the management of chronic myeloid leukemia: 2013. , 2013, Blood.

[17]  C. Cleeland,et al.  Measuring the symptom burden associated with the treatment of chronic myeloid leukemia. , 2013, Blood.

[18]  J. Melo,et al.  Safety and efficacy of imatinib cessation for CML patients with stable undetectable minimal residual disease: results from the TWISTER study. , 2013, Blood.

[19]  Francisco Cervantes,et al.  The price of drugs for chronic myeloid leukemia (CML) is a reflection of the unsustainable prices of cancer drugs: from the perspective of a large group of CML experts. , 2013, Blood.

[20]  R. Larson,et al.  Prediction of outcomes in patients with Ph+ chronic myeloid leukemia in chronic phase treated with nilotinib after imatinib resistance/intolerance , 2013, Leukemia.

[21]  M. Weinstein,et al.  Economic Savings Versus Health Losses: The Cost-Effectiveness of Generic Antiretroviral Therapy in the United States , 2013, Annals of Internal Medicine.

[22]  W. Cullen,et al.  A review of the differences and similarities between generic drugs and their originator counterparts, including economic benefits associated with usage of generic medicines, using Ireland as a case study , 2013, BMC Pharmacology and Toxicology.

[23]  F. Mahon Is going for cure in chronic myeloid leukemia possible and justifiable? , 2012, Hematology. American Society of Hematology. Education Program.

[24]  N. Majhail,et al.  Costs and cost-effectiveness of hematopoietic cell transplantation. , 2012, Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation.

[25]  H. Grabowski,et al.  Longer Patents for Increased Generic Competition in the US , 2012, PharmacoEconomics.

[26]  B. Motheral Pharmaceutical Step-Therapy Interventions: A Critical Review of the Literature , 2011, Journal of managed care pharmacy : JMCP.

[27]  M. Baccarani,et al.  Health-related quality of life in chronic myeloid leukemia patients receiving long-term therapy with imatinib compared with the general population. , 2011, Blood.

[28]  K. Rezvani,et al.  Poor adherence is the main reason for loss of CCyR and imatinib failure for chronic myeloid leukemia patients on long-term therapy. , 2010, Blood.

[29]  Martin C. Müller,et al.  Long-term prognostic significance of early molecular response to imatinib in newly diagnosed chronic myeloid leukemia: an analysis from the International Randomized Study of Interferon and STI571 (IRIS). , 2010, Blood.

[30]  Philippe Rousselot,et al.  Discontinuation of imatinib in patients with chronic myeloid leukaemia who have maintained complete molecular remission for at least 2 years: the prospective, multicentre Stop Imatinib (STIM) trial. , 2010, The Lancet. Oncology.

[31]  Ricardo Pasquini,et al.  Nilotinib versus imatinib for newly diagnosed chronic myeloid leukemia. , 2010, The New England journal of medicine.

[32]  D. Marin,et al.  Adherence is the critical factor for achieving molecular responses in patients with chronic myeloid leukemia who achieve complete cytogenetic responses on imatinib. , 2010, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[33]  M. Gordon Dasatinib versus Imatinib in Newly Diagnosed Chronic-Phase Chronic Myeloid Leukemia , 2010 .

[34]  A. Levy,et al.  A multinational study of health state preference values associated with chronic myelogenous leukemia. , 2010, Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research.

[35]  J. Radich,et al.  International randomized study of interferon Vs STI571 (IRIS) 8-year follow up: Sustained survival and low risk for progression or events in patients with newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP) treated with imatinib , 2009 .

[36]  M. Duh,et al.  Projected economic impact of clinical findings of generic entry of topiramate on G4 European countries , 2009, Current medical research and opinion.

[37]  P. Martiat,et al.  Prevalence, determinants, and outcomes of nonadherence to imatinib therapy in patients with chronic myeloid leukemia: the ADAGIO study. , 2009, Blood.

[38]  K. Rezvani,et al.  European LeukemiaNet criteria for failure or suboptimal response reliably identify patients with CML in early chronic phase treated with imatinib whose eventual outcome is poor. , 2008, Blood.

[39]  R M Stone,et al.  Dasatinib induces durable cytogenetic responses in patients with chronic myelogenous leukemia in chronic phase with resistance or intolerance to imatinib , 2008, Leukemia.

[40]  Francisco Cervantes,et al.  Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia. , 2006, The New England journal of medicine.

[41]  Michael R. Ward,et al.  Generic Drug Industry Dynamics , 2002, Review of Economics and Statistics.

[42]  S. Wiggins,et al.  Price Competition in Pharmaceuticals: The Case of Anti-infectives , 2004 .

[43]  Susan Branford,et al.  Frequency of major molecular responses to imatinib or interferon alfa plus cytarabine in newly diagnosed chronic myeloid leukemia. , 2003, The New England journal of medicine.

[44]  Francisco Cervantes,et al.  Imatinib compared with interferon and low-dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukemia. , 2003, The New England journal of medicine.

[45]  M. Gold Cost-effectiveness in health and medicine , 2016 .

[46]  Henry G. Grabowski,et al.  Brand Loyalty, Entry, and Price Competition in Pharmaceuticals after the 1984 Drug Act , 1992, The Journal of Law and Economics.