Comparative evaluation of patients newly initiating first-generation versus second-generation tyrosine kinase inhibitors for chronic myeloid leukemia and medication adherence, health services utilization, and healthcare costs

Curr Med Res Opin. 2015 Feb;31(2):289-97. doi: 10.1185/03007995.2014.991440. Epub 2014 Dec 10.


Background: Chronic myeloid leukemia (CML) treatment guidelines recommend first-line therapy with either first- or second-generation tyrosine kinase inhibitors (1GTKI, 2GTKI), but do not specify which generation should be used first.

Objective: To examine the association between initiation of 2GTKI versus 1GTKI and medication adherence, health services utilization, and healthcare costs.

Method: This was a retrospective cohort study utilizing administrative claims data from a single health plan within the US of commercial and Medicare patients newly initiating 1GTKI or 2GTKI therapy for CML between June 2010 and December 2011. Multivariate logistic regression was used to investigate the association between TKI therapy and adherence, defined as proportion of days covered ≥0.85. Multivariate logistic regression and generalized linear models examined the association between TKI and health services utilization and direct healthcare costs (plan and patient paid) during the 12 month follow-up period.

Results: Among the 368 patients included, there was no difference in adherence between patients initiating a 2GTKI compared to a 1GTKI (odds ratio = 0.88, 95% confidence interval [CI] 0.55-1.40). Initiating a 2GTKI was associated with increased outpatient visits (incidence rate ratio [IRR] = 1.12, 95% CI 1.06-1.20); however, there were no statistically significant differences in emergency room visits or inpatient visits between the treatment groups. Total costs were 1.3 times higher for 2GTKI initiators versus 1GTKI initiators ($86,509 versus $66,443; p = 0.001), with a significant difference in TKI pharmacy costs.

Conclusions: Although there were no differences in adherence, hospitalizations, or emergency room visits among patients initiating a second- versus first-generation TKI, total all-cause costs and outpatient visits were higher for 2GTKI initiators. With the impending release of generic imatinib, these comparative data will become germane in the selection of a first-line TKI therapy. Because this study used claims from a single health plan, it may not be generalizable to the general population.

Keywords: Adherence; Chronic myeloid leukemia; Healthcare costs; Tyrosine kinase inhibitors.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antineoplastic Agents / economics
  • Antineoplastic Agents / therapeutic use
  • Benzamides* / economics
  • Benzamides* / therapeutic use
  • Cohort Studies
  • Dasatinib
  • Drug Costs
  • Drug Resistance, Neoplasm
  • Female
  • Humans
  • Imatinib Mesylate
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive* / drug therapy
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive* / economics
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive* / epidemiology
  • Male
  • Medication Adherence / statistics & numerical data
  • Middle Aged
  • Odds Ratio
  • Outcome Assessment, Health Care
  • Patient Care / economics
  • Patient Care / methods
  • Patient Care / statistics & numerical data
  • Piperazines* / economics
  • Piperazines* / therapeutic use
  • Protein-Tyrosine Kinases / antagonists & inhibitors
  • Pyrimidines* / economics
  • Pyrimidines* / therapeutic use
  • Retrospective Studies
  • Thiazoles* / economics
  • Thiazoles* / therapeutic use
  • United States / epidemiology


  • 4-methyl-N-(3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)phenyl)-3-((4-pyridin-3-ylpyrimidin-2-yl)amino)benzamide
  • Antineoplastic Agents
  • Benzamides
  • Piperazines
  • Pyrimidines
  • Thiazoles
  • Imatinib Mesylate
  • Protein-Tyrosine Kinases
  • Dasatinib