title: Increasing economic burden of tyrosine kinase inhibitor treatment failure by line of therapy in chronic myeloid leukemia.
abstract: OBJECTIVE
  To assess the economic burden of tyrosine kinase inhibitor (TKI) treatment failure in chronic myeloid leukemia (CML), by assessing all-cause health care resource use (HCRU) and costs in the year after treatment failure by line of therapy (LOT; 1L/2L/3L) using real-world data.
  
  
  METHODS
  Treatment episodes initiating a TKI of interest (index TKI) during June 2008-December 2011 were identified from the IMS PharMetrics Plus Health Plan Claims Database for adult patients with CML diagnosis (ICD-9-CM 205.1x), 120 days pre-index continuous enrollment (CE) and no clinical trial participation. Episodes experiencing treatment failure, defined as switch to a non-index TKI or discontinuation of index TKI (gap of ≥ 60 days), and with 1 year CE post-failure, were analyzed. LOT was determined by number of unique TKIs used in the pre-index. All-cause HCRU and costs (2012 USD) in the 1 year post-failure were assessed by LOT, and the comparisons between 1L and 2L failures were also adjusted using multivariate generalized linear models (GLMs) to control for underlying differences.
  
  
  RESULTS
  A total of 706 episodes were identified (518 1L; 180 2L; 8 3L). Unadjusted HCRU over 1 year post-failure increased significantly. This was accompanied by a significant increase in unadjusted mean costs for 2L failures vs. 1L failures ($99,624 vs. $78,667, p = 0.021, Δ$20,957). Following the adjustment using GLMs, adjusted mean costs were 38% higher (95% CI 1.14-1.68), driven primarily by use of medical services. In adjusted analyses, compared to 1L, 2L failures had: 45% more ambulatory visits (mean 31 vs. 21, 95% CI 1.26-1.66), 75% higher risk of hospitalization (33% vs. 23% hospitalized, 95% CI 1.16-2.64), and 73% higher medical costs (95% CI 1.31-2.29). Medical costs comprised a greater proportion of total costs in 2L vs. 1L (55% vs. 44%); pharmacy costs did not increase significantly.
  
  
  CONCLUSIONS
  The economic burden over 1 year post TKI failure increased with each sequential line of TKI treatment failure.
authors.affiliation: a a ARIAD Pharmaceuticals Inc. , Cambridge , MA , USA.
authors.forename: Lisa J
authors.initials: LJ
authors.lastname: McGarry
authors.affiliation: b b IMS Health , Fairfax , VA , USA.
authors.forename: Yaozhu J
authors.initials: YJ
authors.lastname: Chen
authors.affiliation: b b IMS Health , Fairfax , VA , USA.
authors.forename: Victoria
authors.initials: V
authors.lastname: Divino
authors.affiliation: b b IMS Health , Fairfax , VA , USA.
authors.forename: Shibani
authors.initials: S
authors.lastname: Pokras
authors.affiliation: a a ARIAD Pharmaceuticals Inc. , Cambridge , MA , USA.
authors.forename: Catherine R
authors.initials: CR
authors.lastname: Taylor
authors.affiliation: b b IMS Health , Fairfax , VA , USA.
authors.forename: Julie
authors.initials: J
authors.lastname: Munakata
authors.affiliation: a a ARIAD Pharmaceuticals Inc. , Cambridge , MA , USA.
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Nieset
authors.affiliation: a a ARIAD Pharmaceuticals Inc. , Cambridge , MA , USA.
authors.forename: Hui
authors.initials: H
authors.lastname: Huang
authors.affiliation: c c MD Anderson Cancer Center , Houston , TX , USA.
authors.forename: Elias
authors.initials: E
authors.lastname: Jabbour
authors.affiliation: d d University of Arizona College of Pharmacy , Tucson , AZ , USA.
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Malone
mesh_terms: D000328:Adult; D000368:Aged; D003365:Costs and Cost Analysis; D016208:Databases, Factual; D005260:Female; D006760:Hospitalization / Q000191:economics; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy*; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D012189:Retrospective Studies; D017211:Treatment Failure
chemical_list: D047428:Protein Kinase Inhibitors; D011505:Protein-Tyrosine Kinases
keywords: Chronic myeloid leukemia; Cost analysis; Economic cost; Health services research; Retrospective data; Treatment failure