Predictors of Treatment Non-Adherence in Patients Treated with Imatinib Mesylate for Chronic Myeloid Leukemia.

Imatinib mesylate (IM), an oral tyrosine kinase inhibitor, is now standard front line therapy for the treatment of patients with chronic myeloid leukemia (CML). As demonstrated in the IRIS trial, IM has a 7-year over-all survival rate of 86%. While treatment with IM is effective, adherence among patients receiving IM is suboptimal.

A retrospective cohort study was performed using Medstat Marketscan employer-based data from Jan 1, 2004 through October 1, 2008 for the purposes of identifying key factors associated with patients who are non-adherent to IM. Patients included in the study were adult patients below age 65, with a diagnosis of CML (ICD-9 205.1x), received two or more prescriptions for IM treatment, and are continuously eligible in the health plan. Patients were required to have a 12-month follow-up data of their complete medical and pharmacy events from their first IM prescription in the study period. Independent variables examined included patient demographics, CML disease complexity, frequency of medical treatment received for adverse events, plan type (PPO/HMO), duration of time on IM, duration of time between CML diagnosis and initiation of IM, average daily dose of starting IM, use of chemotherapies prior to initiation of IM, comorbid conditions, bone marrow/stem cell treatment, and the average percent of patient copayment. Patient adherence to IM treatment was measured by calculating average medication possession ratio (MPR) over the 12-month period. Patients were categorized as adhering to the treatment if they maintained on average an MPR of >85%. A sensitivity analysis was performed utilizing an MPR cut-off of 80%. Descriptive and multivariate statistics were conducted. Logistic regression models were developed to determine the factors that influenced odds of achieving an 80% and 85%, adherence rates.

A total of 522 patients had a CML diagnosis and received two or more prescriptions of IM treatment. After applying the exclusion criteria, the final sample included data from 430 patients. The mean age of the patients was 49 years and majority were male (54%). Only 15% of patients received additional chemotherapy during the study period. The number of unique medications consumed by patients averaged 14. The mean MPR in this patient group was 80%, with only 60% of patients categorized as adherent based on MPR of >85%. The following factors were found to be significantly associated with patients who had an MPR of '85%: lower age (p<0.05), shorter exposure to IM (p<0.001), starting IM dose of ≤400 mg (p<0.005), longer time lag between CML diagnosis to IM prescription fill (p<0.0005), higher concomitant prescriptions (p<0.05), and higher percentage of copayment (p<0.01).

Approximately 40% of patients receiving IM treatment were categorized as non-adherent to the treatment. Understanding the factors associated with failure to adhere to the treatment regimen will help physicians assess and educate patients receiving CML treatment. Our findings suggest that duration on IM treatment, time lag between CML diagnosis and IM index date, starting IM dose, and patient cost-sharing to be strong predictors of IM non-adherence, suggesting a need for monitoring of these areas within patients with CML. Persistent monitoring, ongoing dialogue, and appropriate IM dosing is crucial to achieving optimal patient adherence in patients with CML.

StCharles:Novartis Pharmaceuticals Corporation: Research Funding. Bollu:Novartis Pharmaceuticals Corporation: Employment. Hornyak:Novartis Pharmaceuticals Corporation: Employment. Coombs:Novartis Pharmaceuticals Corporation: Employment. Blanchette:Novartis Pharmaceuticals Corporation: Research Funding. DeAngelo:Enzon Pharmaceuticals: Research Funding; Celgene: Speakers Bureau; Bristol-Meyers Squibb: Speakers Bureau; Novartis: Speakers Bureau.