Healthcare resource utilization and costs associated with non-adherence to imatinib treatment in chronic myeloid leukemia patients

Abstract Background: Patients with chronic myeloid leukemia (CML) who do not adhere to treatment may experience suboptimal outcomes. Objective: To examine the association between adherence with imatinib and direct healthcare costs and resource utilization in a large group of privately insured CML patients. Patients and methods: CML patients under age 65 were identified with ICD-9 code 205.1X using MarketScan Commercial Claims data between 1/1/02 and 7/31/08. Patients were required to be continuously enrolled in a private insurance plan during the baseline and study periods, defined respectively as the 4 months prior to and the 12 months following imatinib initiation. Non-adherence was evaluated by the medication possession ratio (MPR), defined as the fraction of days during the study period that patients had filled prescriptions for imatinib, and stratified into two groups (low MPR: <85%, high MPR: ≥85%). Costs, inpatient admissions, and hospital days were compared between high and low adherence groups using Wilcoxon tests. Regression models compared utilization and costs controlling for age, sex, CML severity, Charlson comorbidity index, baseline costs, and other factors. Results: The study sample consisted of 592 patients, where 242 (40.9%) patients were classified with a low MPR, while 350 (59.1%) had a high MPR. Mean MPR was 79% (95% confidence interval 76–81%). Patients with a low MPR incurred more all-cause inpatient visits (4.1 vs. 0.4; p < 0.001) and all-cause inpatient days (14.8 vs. 1.8; p < 0.001). Regression models demonstrated a 283% increase (US$56 324; p < 0.001) in non-imatinib costs within the low- vs. high-MPR group. The generalizability of this study is limited by the use of a privately insured population under 65 years of age as well as by the limitations common to claims data analyses. Conclusions: Imatinib adherence is an important issue for patients and physicians. Better imatinib adherence was associated with significantly lower resource utilization and costs in CML patients, as lower imatinib costs in low MPR patients were more than offset by higher non-imatinib costs mostly driven by inpatient services.

[1]  Susan O'Brien,et al.  NCCN clinical practice guidelines in oncology: chronic myelogenous leukemia. , 2009, Journal of the National Comprehensive Cancer Network : JNCCN.

[2]  L. Staudt,et al.  Clinical Trials and Observations , 2007 .

[3]  J. Radich,et al.  Six-year follow-up of patients receiving imatinib for the first-line treatment of chronic myeloid leukemia , 2009, Leukemia.

[4]  M Kalder,et al.  Adherence to adjuvant endocrine therapy in postmenopausal women with breast cancer. , 2008, Annals of oncology : official journal of the European Society for Medical Oncology.

[5]  C. Shanley,et al.  Cytogenetic Response in Relation to the Adherence to Treatment with Imatinib Mesylate: A Case Control Study. , 2007 .

[6]  S. Kane Just a Spoonful of Sugar Helps the Medicine Go Down…If Only It Was That Simple! Nonadherence in Inflammatory Bowel Disease , 2007, The American Journal of Gastroenterology.

[7]  Nicholas Moore,et al.  Trough imatinib plasma levels are associated with both cytogenetic and molecular responses to standard-dose imatinib in chronic myeloid leukemia. , 2007, Blood.

[8]  G. Guyatt,et al.  Adherence to antiretroviral therapy in sub-Saharan Africa and North America: a meta-analysis. , 2006, JAMA.

[9]  F. Camacho,et al.  Comparison of medication adherence and associated health care costs after introduction of pioglitazone treatment in African Americans versus all other races in patients with type 2 diabetes mellitus: a retrospective data analysis. , 2006, Clinical therapeutics.

[10]  C. Pashos,et al.  Prevalence and economic consequences of medication adherence in diabetes: a systematic literature review. , 2006, Managed care interface.

[11]  J. Tsang,et al.  Prescription compliance and persistency in chronic myelogenous leukemia (CML) and gastrointestinal stromal tumor (GIST) patients (pts) on imatinib (IM). , 2006, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[12]  Timothy L. Lash,et al.  Adherence to tamoxifen over the five-year course , 2006, Breast Cancer Research and Treatment.

[13]  A. Lippman Adherence to medication. , 2005, The New England journal of medicine.

[14]  Rishi Sikka,et al.  Estimating medication persistency using administrative claims data. , 2005, The American journal of managed care.

[15]  R. Verbrugge,et al.  Impact of Medication Adherence on Hospitalization Risk and Healthcare Cost , 2005, Medical care.

[16]  Martin C. Müller,et al.  Response and resistance in 300 patients with BCR‐ABL–positive leukemias treated with imatinib in a single center , 2005, Cancer.

[17]  L. Wodicka,et al.  A small molecule–kinase interaction map for clinical kinase inhibitors , 2005, Nature Biotechnology.

[18]  M. Baccarani,et al.  Imatinib and pegylated human recombinant interferon-alpha2b in early chronic-phase chronic myeloid leukemia. , 2004, Blood.

[19]  Aliza K Fink,et al.  Patient beliefs and tamoxifen discontinuance in older women with estrogen receptor--positive breast cancer. , 2004, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[20]  C. Sandoval,et al.  Imatinib mesylate noncompliance simulating chronic myeloid leukemia resistance. , 2003, Journal of pediatric hematology/oncology.

[21]  Jerry Avorn,et al.  Nonadherence to adjuvant tamoxifen therapy in women with primary breast cancer. , 2003, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[22]  H. Kantarjian,et al.  Imatinib mesylate (STI571) therapy for Philadelphia chromosome-positive chronic myelogenous leukemia in blast phase. , 2002, Blood.

[23]  E. Winer,et al.  Adherence to therapy with oral antineoplastic agents. , 2002, Journal of the National Cancer Institute.

[24]  M. Baccarani,et al.  Imatinib induces durable hematologic and cytogenetic responses in patients with accelerated phase chronic myeloid leukemia: results of a phase 2 study. , 2002, Blood.

[25]  M. Baccarani,et al.  Hematologic and cytogenetic responses to imatinib mesylate in chronic myelogenous leukemia. , 2002, The New England journal of medicine.

[26]  C. Sawyers,et al.  Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia. , 2001, The New England journal of medicine.

[27]  T. Lash,et al.  Adjuvant tamoxifen: predictors of use, side effects, and discontinuation in older women. , 2001, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[28]  W. Manning,et al.  Estimating Log Models: To Transform or Not to Transform? , 1999, Journal of health economics.

[29]  W. Manning,et al.  The logged dependent variable, heteroscedasticity, and the retransformation problem. , 1998, Journal of health economics.

[30]  J. Mullahy Much Ado About Two: Reconsidering Retransformation and the Two-Part Model in Health Economics , 1998, Journal of health economics.

[31]  Jürg Zimmermann,et al.  Effects of a selective inhibitor of the Abl tyrosine kinase on the growth of Bcr–Abl positive cells , 1996, Nature Medicine.

[32]  E. Canaani,et al.  Chronic myelogenous leukemia: biology and therapy. , 1993, Leukemia.

[33]  R. Deyo,et al.  Adapting a clinical comorbidity index for use with ICD-9-CM administrative databases. , 1992, Journal of clinical epidemiology.

[34]  K B McCredie,et al.  Characteristics of accelerated disease in chronic myelogenous leukemia , 1988, Cancer.

[35]  J. Sokal Prognosis in chronic myeloid leukaemia: biology of the disease vs. treatment. , 1987, Bailliere's clinical haematology.

[36]  G. Daley,et al.  The chronic myelogenous leukemia-specific P210 protein is the product of the bcr/abl hybrid gene. , 1986, Science.

[37]  I. Litt,et al.  Compliance with therapeutic regimens. , 1984, Journal of adolescent health care : official publication of the Society for Adolescent Medicine.

[38]  H. Black Compliance With Therapeutic Regimens , 1978, The Yale Journal of Biology and Medicine.

[39]  T. Papayannopoulou,et al.  Chronic myelocytic leukemia: clonal origin in a stem cell common to the granulocyte, erythrocyte, platelet and monocyte/macrophage. , 1977, The American journal of medicine.

[40]  M. Becker,et al.  Sociobehavioral Determinants of Compliance with Health and Medical Care Recommendations , 1975, Medical care.

[41]  J. Rowley A New Consistent Chromosomal Abnormality in Chronic Myelogenous Leukaemia identified by Quinacrine Fluorescence and Giemsa Staining , 1973, Nature.

[42]  B. Blackwell The drug defaulter , 1972, Clinical pharmacology and therapeutics.

[43]  P. Nowell,et al.  Chromosome studies on normal and leukemic human leukocytes. , 1960, Journal of the National Cancer Institute.

[44]  W. Feng,et al.  Treatment Interruptions and Non-Adherence with Imatinib and Associated Healthcare Costs , 2012, PharmacoEconomics.

[45]  J. Radich,et al.  Six-year follow-up of patients receiving imatinib for the first-line treatment of chronic myeloid leukemia , 2010, Leukemia.

[46]  David M. Adamson,et al.  HealtH ReseaRcH Data foR tHe Real WoRlD: tHe MaRketscan ® Databases , 2008 .

[47]  J. Garcia-conde,et al.  Imatinib mesylate therapy of chronic phase chronic myeloid leukemia resistant or intolerant to interferon: results and prognostic factors for response and progression-free survival in 150 patients. , 2003, Haematologica.

[48]  J. Strain,et al.  Patient noncompliance with self‐administered chemotherapy , 1990, Cancer.

[49]  R. Greenberg Overview of patient compliance with medication dosing: a literature review. , 1984, Clinical therapeutics.