Adherence to treatment with second-line therapies, dasatinib and nilotinib, in patients with chronic myeloid leukemia

Abstract

Background and objective:

Previous studies have shown that long-term outcomes are more favorable for patients newly diagnosed with chronic myeloid leukemia (CML) if a complete cytogenetic response is achieved within ≤12 months of diagnosis. Because continuous and adequate dosing is important to achieve this outcome, it is important to understand treatment adherence as part of managing long-term CML therapy. While studies regarding imatinib suggest that adherence varies widely, data addressing adherence to newer breakpoint cluster region–Abelson (BCR-ABL) inhibitors (dasatinib and nilotinib) are sparse. This study evaluates real-world adherence in patients diagnosed with CML receiving dasatinib or nilotinib as second-line therapy.

Research design and methods:

Using the HealthCore Integrated Research Database (HIRD^SM), patients with ≥1 International Classification of Diseases, 9th edition/revision, Clinical Modification (ICD-9-CM) code for CML (205.1x ) and ≥1 prescription for imatinib from January 1, 2001 to June 30, 2010 were identified. Analysis was limited to patients who switched to second-line dasatinib or nilotinib. Dasatinib exposure was stratified by dose (≤100 mg/day or ≥140 mg/day) to account for dasatinib label changes.

Main outcome measures:

Medication possession ratio (MPR) was used to calculate adherence and Cox proportional hazard models were used to quantify poor rates of adherence (i.e. MPR <85%).

Results:

Of 2064 imatinib-exposed patients, 197 received dasatinib (≤100 mg/day, n = 112; ≥140 mg/day, n = 85) and 53 received nilotinib (400 mg BID, n = 46; 400 mg QD, n = 7) as second-line therapy. Mean exposure durations were 276 days for dasatinib (≤100 mg, 275 days; ≥140 mg, 276 days) and 170 days for nilotinib. Cox proportional hazard models quantifying rates of poor adherence (MPR < 85%) comparing nilotinib with dasatinib (adjusted for age, sex, duration of previous imatinib exposure, number of concomitant medications, presence of cardiovascular disease or diabetes) calculated hazard ratios of 1.6 (95% confidence interval [CI], 1.0–2.4) for nilotinib versus dasatinib overall, 1.9 (95% CI, 1.2–3.0) for nilotinib versus dasatinib ≤100 mg, and 1.2 (95% CI, 0.7–2.0) for nilotinib versus dasatinib ≥140 mg.

Conclusions:

While this study is limited by use of claims data to identify CML and adherence, claims based data have been widely used to evaluate the association between treatment use and clinical outcomes. When stratified by dose, patients receiving second-line nilotinib were almost two times more likely to have poor adherence compared with patients receiving second-line dasatinib at the current approved dose of 100 mg once daily.

Key words::

• BCR-ABL inhibitors
• Chronic myelogenous leukemia
• Medication adherence
• Second-line therapy

Transparency

Declaration of funding

This study was funded by a grant from Bristol-Myers Squibb (BMS) Company.

Declaration of financial/other relationships

M.U.Y. and S.A.O. have disclosed that they are employees of EpiSource, LLC, a company that received funding from BMS to conduct this study. I.H. and C.D. have disclosed that they were employees of BMS at the time this study was conducted and hold stock in BMS. M.C. has disclosed that he is an employee of HealthCore Inc., a company that received funding from BMS to help conduct this study. M.H. has disclosed that he is a consultant to EpiSource, LLC.

CMRO peer reviewers may have received honoraria for their review work. The peer reviewers on this manuscript have disclosed that they have no relevant financial relationships.

The sponsors of this project had the right of commenting but the authors retained the right to accept or reject the comments or suggestions. Final decisions and authority regarding manuscript content and submission contractually remained with M.U.Y., S.A.O., M.C. and M.H.

Acknowledgments

The authors are grateful to Syd Phillips MPH and Deb Casso MPH for their assistance in manuscript preparation.

Previous presentation: results from this study were presented as a poster at the 2010 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, IL, USA.