Healthcare and economic burden of adverse events among patients with chronic myelogenous leukemia treated with BCR-ABL1 tyrosine kinase inhibitors

Objectives: BCR-ABL1 tyrosine kinase inhibitors (TKIs) are established treatments for chronic myelogenous leukemia (CML); however, they are associated with infrequent, but clinically serious adverse events (AEs). The objective of this analysis was to assess healthcare resource utilization and costs associated with AEs, previously identified using the FDA Adverse Event Reporting System (FAERS) in another study, among TKI-treated patients.

Methods: Adult patients with ≥1 inpatient or ≥2 outpatient ICD-9-CM diagnosis codes for CML and ≥1 claim for a TKI treatment between January 1, 2006 and September 30, 2012 were identified from the Commercial and Medicare MarketScan databases. The first claim for a TKI was designated as the index event. Patients were required to have no TKI treatment during a 12-month baseline period. Healthcare resource utilization and costs associated with select AEs having the strongest association with TKI treatment (femoral arterial stenosis [FAS], peripheral arterial occlusive disease [PAOD], intermittent claudication, coronary artery stenosis [CAS], pericardial effusion, pleural effusion, malignant pleural effusion, conjunctival hemorrhage) were evaluated during a 12-month follow-up period.

Results: The study sample included 2,005 CML patients receiving TKI therapy (mean age?=?56 years; 56% male). Among all evaluated AEs, the highest mean inpatient healthcare costs were observed for FAS ($16,800 per patient) and PAOD ($14,263 per patient), which had total mean medical costs (inpatient?+?outpatient) of $17,015 and $15,154 per patient, respectively. Mean outpatient healthcare costs were highest for CAS ($1,861 per patient), followed by intermittent claudication ($947 per patient), PAOD ($891 per patient), and pleural effusion ($890 per patient). Total mean medical costs for fluid retention-related AEs, including pericardial effusion and pleural effusion, were $2,797 and $1,908 per patient, respectively.

Conclusions: The healthcare costs of AEs identified in the FAERS as having the strongest association with TKI treatment are substantial. Vascular stenosis-related AEs, including FAS and PAOD, have the highest cost burden.     

Economic modeling to evaluate the impact of chronic myeloid leukemia therapy management on the oncology care model in the US

Abstract

Objective: To develop an economic model to evaluate changes in healthcare costs driven by restricting usage of branded tyrosine kinase inhibitors (TKIs) through substitution with generic imatinib among chronic myeloid leukemia (CML) patients in a typical Oncology Care Model (OCM) practice, and examine the impact on Performance-Based Payment (PBP) eligibility.

Methods: An Excel-based economic model of an OCM practice with 1,000 cancer patients during a 6-month episode of care was developed. Cancer types and proportions of patients treated in the practice were estimated from an OCM report. All-cause healthcare costs were obtained from published literature. It was assumed that if a practice restricts usage of branded TKIs for newly-diagnosed CML patients, 80% of the market share of branded imatinib and 50% of the market shares of 2^nd-gen TKIs would shift to generic imatinib. Among established TKI-treated patients, it was assumed that 80% of the market share of branded imatinib and no patients treated with 2^nd-gen TKIs would shift to the generic.

Results: Four CML patients were estimated for a 1,000-cancer patient OCM practice with a total baseline healthcare cost of $51,345,812 during a 6-month episode. If the practice restricts usage of branded TKIs, the shift from 2^nd-gen TKIs to generic imatinib would reduce costs by $12,970, while shifting from branded to generic imatinib lowers costs by $25,250 during a 6-month episode. Minimum reductions of $3,013,832 in a one-sided risk model and $2,372,010 in a two-sided risk model are required for PBP eligibility; the shift from 2^nd-gen TKIs to generic imatinib would account for 0.4% and 0.5% of the savings required for a PBP, respectively.

Conclusions: This analysis indicates that the potential cost reduction associated with restricting branded TKI usage among CML patients in an OCM setting will represent only a small proportion of the cost reduction needed for PBP eligibility.     

Estimated medical cost reductions associated with use of novel oral anticoagulants vs warfarin in a real-world non-valvular atrial fibrillation patient population

Objective:

Results of randomized clinical trials (RCT) demonstrate that novel oral anticoagulants (NOAC) are effective therapies for reducing the risk of stroke in non-valvular atrial fibrillation (NVAF). Prior medical cost avoidance studies have used warfarin event rates from RCTs, which may differ from patients receiving treatment in a real-world (RW) setting, where the quality of care may not be the same as in a RCT. The purpose of this study was to estimate the change in medical costs related to stroke and major bleeding for each NOAC (apixaban, dabigatran, and rivoraxaban) relative to warfarin in a RW NVAF population.

Methods:

Patients (n?=?23,525) with a diagnosis of NVAF during 2007–2010 were selected from a Medco population of US health plans. Stroke and major bleeding excluding intracranial hemorrhage (MBEIH) events were identified using diagnosis codes on medical claims. RW reference event rates were calculated during periods of warfarin exposure. RW event rates for NOACs were estimated by multiplying the corresponding relative risk (RR) from the RCTs by each reference rate. Absolute risk reductions (ARR) or number of events avoided per patient year were then estimated. Changes in medical costs associated with each NOAC were calculated by applying the ARR to the 1-year cost for each event. Costs for stroke and MBEIH were obtained from the literature. Drug and international normalized ratio monitoring costs were not considered in this analysis.

Results:

Compared to RW warfarin, use of apixaban and dabigatran resulted in total (stroke plus MBEIH) medical cost reductions of $1245 and $555, respectively, during a patient year. Rivaroxaban resulted in a medical cost increase of $144.

Conclusions:

If relative risk reductions demonstrated in RCTs persist in a RW setting, apixaban would confer the greatest medical cost savings vs warfarin, resulting from significantly lower rates of both stroke and MBEIH.     

Cost-effectiveness analysis of second-line tyrosine kinase inhibitor treatment for chronic myelogenous leukemia

Aim:

A cost-effectiveness analysis was performed for sequential treatments of chronic myelogenous leukemia (CML) with tyrosine kinase inhibitors (TKIs) after failure of 1st line imatinib, from a commercial payer perspective in the US.

Methods:

A Markov model was developed to simulate lifetime treatment costs and health outcomes for TKI sequences for treatment of patients resistant or intolerant to 1st-line imatinib. Five health states were included, chronic phase 2nd-line TKI, chronic phase 3rd-line TKI, chronic phase post-TKI, advanced phases, and death. Efficacy (response achievement, loss of response, transformation, death) and safety (adverse events incidence, discontinuation) data are based on clinical trials. Resource utilization, costs, and utilities were based on product labels and publically available data. Uncertainty analyses were conducted for key inputs.

Results:

In patients failing imatinib, dasatinib-initiating treatment sequences provide the most survival (ΔLYs?=?0.2–2.0), QALYs (ΔQALYs?=?0.2–1.9), and accrue highest CML-related costs (ΔCosts?=?$64,000–$222,000). The average ICER per QALY for dasatinib- vs imatinib-initiating sequences is $100,000 for an imatinib-resistant population. The average ICER per QALY for dasatinib- vs nilotinib-initiating sequences is $170,000 for an imatinib-resistant population, and $160,000 for an imatinib-intolerant population.

Conclusions:

This analysis suggests that dasatinib is associated with increased survival and quality of life compared to high dose imatinib and to a smaller extent with nilotinib, among patients resistant or intolerant to 1st-line imatinib, primarily based on higher cytogenetic response rates observed in clinical studies of dasatinib. Head-to-head studies of sequential use of dasatinib and nilotinib are needed to validate the model findings of improved survival (LYs) with better quality-of-life (QALYs) for patients initiating dasatinib in 2nd-line. However, the model findings (in light of higher cytogenetic response rates with dasatinib) are supported by other studies showing improved quality-of-life for responders, and improved survival for patients achieving cytogenetic response.