Long-term adherence and outcomes of oral Tyrosine Kinase Inhibitors for the treatment of CML in the US VHA medical system

dc.contributor.advisorKoeller, Jimen
dc.contributor.committeeMemberFrei, Christopher Ren
dc.contributor.committeeMemberWilson, James Pen
dc.contributor.committeeMemberShepherd, Marvin Den
dc.contributor.committeeMemberBollinger, Mary Jen
dc.creatorKreys, Eugene Danielen
dc.date.submittedAugust 2014en
dc.description.abstractChronic Myeloid Leukemia (CML) represents about 15-20% of all adult leukemias. The introduction of Tyrosine Kinase Inhibitors (TKIs) was a breakthrough in the treatment of CML that drastically improved outcomes. Poor adherence is recognized to be a major source of treatment failure and is especially concerning in situations where medications are self-administered, as is the case with TKI therapy. Several published studies on patient adherence with oral chemotherapy found rates for long-term treatment to be around 40-50%. The primary purpose of this study was to determine long-term adherence to TKI therapy, and to establish the effect of adherence on the clinical response. A secondary purpose was to compare adherence and treatment outcomes among TKIs. This was a retrospective cohort study of CML patients receiving TKI therapy at any Veteran Health Administration (VHA) facility. Patients 18-89 years of age, with CML diagnosis that filled at least one prescription for imatinib, nilotinib, or dasatinib from 10/1/2001 through 9/30/2010 were included in this study. Adherence was ascertained for 2,873 patients by calculating the Medication Possession Ratio (MPR) using administrative refill data. A manual chart review of 683 patients determined the clinical effectiveness of TKI therapy by identifying cases of major molecular response (MMR), as well as complete cytogenetic response (CCyR). Thirty-three percent of dasatinib-treated patients were adherent during first-year of treatment relative to 28% of nilotinib-treated patients, resulting in an adjusted OR 1.24 (95% CI: 0.78-1.95, p= 0.361). Fifty-one percent of the patients receiving dasatinib as second-line treatment achieved documented MMR by 18 months relative to 56% of nilotinib-treated patients, resulting in an adjusted OR of 0.66 (95% CI: 0.35 -1.23, p= 0.189). Documented MMR by 18 months was achieved by 53% of the patients adherent to TKI therapy relative to 45% of nonadherent patients. When adjusted for covariates, the difference was significant with an OR of 2.68 (95% CI: 1.58 - 4.57, p< 0.001). In conclusion, no significant difference in adherence rates or clinical effectiveness was observed between dasatinib or nilotinib when administered as second-line treatment. Adherence to TKI therapy was found to be significantly associated with improved clinical effectiveness.en
dc.description.departmentPharmaceutical Sciencesen
dc.subjectChronic Meyloid Leukemiaen
dc.subjectTyrosine Kinase Inhibitorsen
dc.subjectMedication adherenceen
dc.subjectVeteran Health Administrationen
dc.titleLong-term adherence and outcomes of oral Tyrosine Kinase Inhibitors for the treatment of CML in the US VHA medical systemen
thesis.degree.departmentPharmaceutical Sciencesen
thesis.degree.disciplinePharmaceutical Sciencesen
thesis.degree.grantorThe University of Texas at Austinen
thesis.degree.nameDoctor of Philosophyen

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