Cost-effectiveness of Tyrosine Kinase Inhibitor Treatment Strategies for Chronic Myeloid Leukemia in Chronic Phase After Generic Entry of Imatinib in the United States
Language English Country United States Media electronic-print
Document type Comparative Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't
Grant support
UL1 TR001111
NCATS NIH HHS - United States
UL1TR001111
NCATS NIH HHS - United States
UL1 TR002489
NCATS NIH HHS - United States
K07-CA138906
NCI NIH HHS - United States
K12 HD001441
NICHD NIH HHS - United States
PubMed
26944912
PubMed Central
PMC4948567
DOI
10.1093/jnci/djw003
PII: djw003
Knihovny.cz E-resources
- MeSH
- Cost-Benefit Analysis MeSH
- Survival Analysis MeSH
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive drug therapy economics mortality MeSH
- Adult MeSH
- Models, Econometric MeSH
- Drugs, Generic * economics therapeutic use MeSH
- Imatinib Mesylate economics therapeutic use MeSH
- Protein Kinase Inhibitors economics therapeutic use MeSH
- Quality-Adjusted Life Years MeSH
- Practice Patterns, Physicians' * standards trends MeSH
- Middle Aged MeSH
- Humans MeSH
- Markov Chains MeSH
- Antineoplastic Agents economics therapeutic use MeSH
- Aged MeSH
- Protein-Tyrosine Kinases antagonists & inhibitors MeSH
- Treatment Outcome MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Research Support, N.I.H., Extramural MeSH
- Comparative Study MeSH
- Geographicals
- United States epidemiology MeSH
- Names of Substances
- Drugs, Generic * MeSH
- Imatinib Mesylate MeSH
- Protein Kinase Inhibitors MeSH
- Antineoplastic Agents MeSH
- Protein-Tyrosine Kinases MeSH
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.
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O’Brien SG, Guilhot F, Larson RA, et al. Imatinib compared with interferon and low-dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukemia. N Engl J Med. 2003;348(11):994–1004. PubMed
Druker BJ, Guilhot F, O’Brien SG, et al. Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia. N Engl J Med. 2006;355(23):2408–2417. PubMed
Hughes TP, Kaeda J, Branford S, et al. Frequency of major molecular responses to imatinib or interferon alfa plus cytarabine in newly diagnosed chronic myeloid leukemia. N Engl J Med. 2003;349(15):1423–1432. PubMed
Deininger M, O’Brien SG, Guilhot F, 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. ASH Annual Meeting Abstracts. 2009;114(22):1126.
Baccarani M, Deininger MW, Rosti G, et al. European LeukemiaNet recommendations for the management of chronic myeloid leukemia: 2013. Blood. 2013;122(6):872–884. PubMed PMC
Cortes J, Saglio G, Baccarani M, 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). ASH Annual Meeting Abstracts. 2014;124(21).
Kantarjian H, Shah NP, Hochhaus A, et al. Dasatinib versus imatinib in newly diagnosed chronic-phase chronic myeloid leukemia. N Engl J Med. 2010;362(24):2260–2270. PubMed
Larson RA, Kim DW, Issaragrisil S, et al. Efficacy and Safety of Nilotinib vs. Imatinib in Patients with Newly Diagnosed Chronic Myeloid Leukemia in Chronic Phase (CML-CP): Long-Term Follow-Up of ENESTnd. ASH Annual Meeting Abstracts. 2014;124(21).
Saglio G, Kim DW, Issaragrisil S, et al. Nilotinib versus imatinib for newly diagnosed chronic myeloid leukemia. N Engl J Med. 2010;362(24):2251–2259. PubMed
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. Blood. 2013;121(22):4439–4442. PubMed PMC
Conti RM. Why are cancer drugs commonly the target of numerous schemes to extend patent exclusivity? Health Affairs Blog. December 4, 2013.
Kantarjian H, Steensma D, Rius Sanjuan J, et al. High cancer drug prices in the United States: reasons and proposed solutions. J Oncol Pract. 2014;10(4):e208-e211. PubMed
Walensky RP, Sax PE, Nakamura YM, et al. Economic savings versus health losses: the cost-effectiveness of generic antiretroviral therapy in the United States. Ann Intern Med. 2013;158(2):84–92. PubMed PMC
Conti RM, Berndt ER. Specialty drug prices and utilization after loss of US patent exclusivity, 2001–2007. In. NBER Working Paper Series 20016: National Bureau of Economic Research (NBER); 2014.
Generic Imatinib. http://cmlsociety.org/generic-tyrosine-kinase-inhibitors-tkis-arrive-in-canada/. Accessed January 30, 2016.
Dunne S, Shannon B, Dunne C, 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. BMC Pharmacol Toxicol. 2013;14:1. PubMed PMC
de Lemos ML, Kyritsis V. Clinical efficacy of generic imatinib. J Oncol Pharm Pract. 2015;21(1):76–79. PubMed
Gold M, Siegel JE, Russell LB, Weinstein MC. Cost-Effectiveness in Health and Medicine. New York: Oxford University Press; 1996.
Hochhaus A, Baccarani M, Deininger M, et al. Dasatinib induces durable cytogenetic responses in patients with chronic myelogenous leukemia in chronic phase with resistance or intolerance to imatinib. Leukemia. 2008;22(6):1200–1206. PubMed
Hughes TP, Saglio G, Kantarjian HM, et al. Early molecular response predicts outcomes in patients with chronic myeloid leukemia in chronic phase treated with frontline nilotinib or imatinib. Blood. 2014;123(9):1353–1360. PubMed PMC
Jabbour E, Kantarjian HM, Saglio G, et al. Early response with dasatinib or imatinib in chronic myeloid leukemia: 3-year follow-up from a randomized phase 3 trial (DASISION). Blood. 2014;123(4):494–500. PubMed PMC
Jabbour E, le Coutre PD, Cortes J, et al. Prediction of outcomes in patients with Ph+ chronic myeloid leukemia in chronic phase treated with nilotinib after imatinib resistance/intolerance. Leukemia. 2013;27(4):907–913. PubMed PMC
Shah NP, Guilhot F, Cortes JE, et al. Long-term outcome with dasatinib after imatinib failure in chronic-phase chronic myeloid leukemia: follow-up of a phase 3 study. Blood. 2014;123(15):2317–2324. PubMed PMC
Marin D, Milojkovic D, Olavarria E, 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. Blood. 2008;112(12):4437–4444. PubMed PMC
Hughes TP, Hochhaus A, Branford S, 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). Blood. 2010;116(19):3758–3765. PubMed PMC
Efficace F, Baccarani M, Breccia M, et al. Health-related quality of life in chronic myeloid leukemia patients receiving long-term therapy with imatinib compared with the general population. Blood. 2011;118(17):4554–4560. PubMed
Williams LA, Garcia Gonzalez AG, Ault P, et al. Measuring the symptom burden associated with the treatment of chronic myeloid leukemia. Blood. 2013;122(5):641–647. PubMed PMC
Szabo SM, Levy AR, Davis C, et al. A multinational study of health state preference values associated with chronic myelogenous leukemia. Value Health. 2010;13(1):103–111. PubMed
Innes AJ, Apperley JF. Chronic Myeloid Leukemia-Transplantation in the Tyrosine Kinase Era. Hematol Oncol Clin North Am. 2014;28(6):1037–1053. PubMed
Padula W, Allen R, Nair K. Determining the cost of obesity and its common comorbidities from a commercial claims database. Clin Obesity. 2014;4(1):53–58. PubMed
Guerin A, Chen L, Dea K, et al. Economic benefits of adequate molecular monitoring in patients with chronic myelogenous leukemia. J Med Econ. 2014;17(2):89–98. PubMed
Preussler JM, Denzen EM, Majhail NS. Costs and cost-effectiveness of hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2012;18(11):1620–1628. PubMed PMC
Conti RM, Padula WV, Larson RA. Changing the cost of care for chronic myeloid leukemia: the availability of generic imatinib in the USA and the EU. Ann Hematol. 2015; In Press. PubMed PMC
Grabowski H, Vernon J. Longer patents for increased generic competition in the US. The Waxman-Hatch Act after one decade. Pharmacoeconomics. 1996;10(Suppl 2):110–123. PubMed
Grabowski H, Vernon J. Brand loyalty, entry and price competition in pharmaceuticals after the 1984 Drug Act. J Law Econ. 1992;35:331–350.
Reiffen D, Ward MR. Generic drug industry dynamics. Rev Econ Statistics. 2005;87(1):37–49.
Wiggins SN, Maness R. Price Competition in Pharmaceuticals: The Case of Anti‐infectives. Econ Inquiry. 2004;42(2):247–263.
Motheral BR. Pharmaceutical step-therapy interventions: a critical review of the literature. J Manag Care Pharm. 2011;17(2):143–155. PubMed PMC
Nayak RK, Pearson SD. The Ethics Of ‘Fail First’: Guidelines And Practical Scenarios For Step Therapy Coverage Policies. Health Affairs. 2014;33(10):1779–1785. PubMed
Pearson CF. Consumers face more hurdles to accessing drugs in exchange plans compared to employer coverage. Washington, DC: Avalere Health; March 2014.
Paradis PE, Latremouille-Viau D, Moore Y, et al. Projected economic impact of clinical findings of generic entry of topiramate on G4 European countries. Curr Med Res Opin. 2009;25(7):1793–1805. PubMed
2013–2014 Prescription Drug Benefit Costs and Plan Design Report. In: Pharmacy Benefit Management Institute; August 2013; Plano, TX.
Ibrahim AR, Eliasson L, Apperley JF, et al. Poor adherence is the main reason for loss of CCyR and imatinib failure for chronic myeloid leukemia patients on long-term therapy. Blood. 2011;117(14):3733–3736. PubMed PMC
Marin D, Bazeos A, Mahon FX, et al. Adherence is the critical factor for achieving molecular responses in patients with chronic myeloid leukemia who achieve complete cytogenetic responses on imatinib. J Clin Oncol. 2010;28(14):2381–2388. PubMed PMC
Noens L, van Lierde MA, De Bock R, et al. Prevalence, determinants, and outcomes of nonadherence to imatinib therapy in patients with chronic myeloid leukemia: the ADAGIO study. Blood. 2009;113(22):5401–5411. PubMed
Dusetzina SB, Winn AN, Abel GA, et al. Cost sharing and adherence to tyrosine kinase inhibitors for patients with chronic myeloid leukemia. J Clin Oncol. 2014;32(4):306–311. PubMed
Mahon FX, Rea D, Guilhot J, 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. Lancet Oncol. 2010;11(11):1029–1035. PubMed
Rousselot P, Charbonnier A, Cony-Makhoul P, 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. J Clin Oncol. 2014;32(5):424–430. PubMed
Delphine R, Nicolini F, Tulliez M, et al. Dasatinib or nilotinib discontinuation in chronic phase-chronic myeloid leukemia patients with durably undetectable BCR-ABL transcripts: Interim analysis of the STOP 2G-TKI study with a minimum follow-up of 12 months – on Behalf of the French CML Group FILMC. ASH Annual Meeting Abstracts. 2014;124(21).
Ross DM, Branford S, Seymour JF, et al. Safety and efficacy of imatinib cessation for CML patients with stable undetectable minimal residual disease: results from the TWISTER study. Blood. 2013;122(4):515–522. PubMed
Mahon FX, Etienne G. Deep molecular response in chronic myeloid leukemia: the new goal of therapy? Clin Cancer Res. 2014;20(2):310–322. PubMed
Mahon FX. Is going for cure in chronic myeloid leukemia possible and justifiable? Hematology Am Soc Hematol Educ Program. 2012;2012:122–128. PubMed