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