Higher Copayment Associated With Greater Discontinuation of and Nonadherence to Tyrosine Kinase Inhibitor Treatment in CML


Key Points

  • Patients with higher copayments were 70% more likely to discontinue tyrosine kinase inhibitor therapy.
  • Patients with higher copayments were 42% more likely to be nonadherent to tyrosine kinase inhibitor therapy.

The availability of the tyrosine kinase inhibitor imatinib (Gleevec) has dramatically increased survival in chronic myeloid leukemia (CML). Nonadherence to therapy with imatinib and other tyrosine kinase inhibitors is associated with disease progression and treatment resistance. In a study reported in the Journal of Clinical Oncology, Dusetzina et al evaluated trends in imatinib expenditures from 2002 to 2011 and the association between copayment requirements for imatinib and tyrosine kinase inhibitors adherence. They found that patients with higher copayments are more likely to be nonadherent to or discontinue tyrosine kinase inhibitor treatment.

Study Details

The study involved review of MarketScan health plan claims from 2002 to 2011 to identify 1,541 patients aged 18 to 64 years with CML who started imatinib therapy between January 2002 and June 2011 and had insurance coverage for ≥ 3 months before and ≥ 6 months after treatment initiation. The primary outcomes were tyrosine kinase inhibitor discontinuation and nonadherence. The primary independent variable was out-of-pocket cost for a 30-day supply of imatinib.

A propensity-score weighted sample was used to estimate risk of discontinuation and nonadherence for patients with higher (top quartile) vs lower copayments. The propensity score was derived by modeling the probability of having higher vs lower copayments as a function of control variables including age, insurance type, region, and enrollee relationship to employee, measured in the month of starting therapy, as well as the Klabunde modification of the Charlson comorbidity score and number of medication classes used preceding treatment initiation, measured during the 3 months prior to the start of therapy.


Copayment requirements consisted of coinsurance for imatinib for 6% of patients and copayment for 88.5%. The mean expenditure for a 30-day supply of imatinib was $286 (median, $50) for patients with coinsurance requirements. Costs varied substantially, with 6% of patients paying > $500 for a 30-day supply.

Over the study period, the mean copayment for a 30-day supply of imatinib was $108, with a median of $30 and a range of $0% to $4,792. Mean monthly copayments varied widely, with patients in the bottom 25th percentile paying $17 and those in the top 75th percentile paying $53. Monthly copayments increased from an average of $55 in 2002 to $145 in 2010. Mean monthly total expenditure for imatinib increased from $2,798 in 2002 to $4,892 in 2011 ($2,846 to $4,954 for median expenditure).

Before propensity-score weighting, patients with relatively lower imatinib copayment requirements (lowest 3 quartiles, n = 1,134) and those with higher requirements (upper quartile, n = 407) were generally balanced for age (mean, 49 and 48 years), sex (44% and 46% female), relationship of patient to employee (66.5% and 69% employee), starting imatinib dose (≤ 400 mg in 89% in both), number of medications in 3 months before start of treatment (mean, 5.5 and 5.3), and Charlson comorbidity score (0 in 94% and 95%). Patients with higher copayment requirements were significantly less likely to live in the Northeast (13% vs 8%, P = .01 for trend) and significantly more likely to have a preferred provider organization health plan (57% vs 68%, P < .001 for trend). After propensity-score weighting, there were no differences between groups in any of these characteristics.

Association With Discontinuation and Nonadherence

On adjusted analysis, 10% of patients with lower copayment requirements and 17% with higher requirements discontinued therapy during the first 180 days after treatment initiation, representing a 70% increase in risk of discontinuing tyrosine kinase inhibitors in those with higher copayments (adjusted risk ratio [RR] = 1.70, 95% confidence interval [CI] = 1.30–2.22). Similarly, patients with higher copayments were significantly more likely to be nonadherent with tyrosine kinase inhibitor therapy, defined as < 80% of days with drug available (21% vs 30%, adjusted RR = 1.42, 95% CI = 1.19–1.69). Patients with lower copayments had a significantly greater number of days covered by medication supply (87% vs 82%, adjusted risk difference = −0.05, 95% CI = −0.07 to −0.02), but there was no difference between groups when patients who discontinued medication were excluded from analysis (93% vs 92%, adjusted risk difference = −0.01, P = .15).

The investigators concluded, “Patients with higher copayments are more likely to discontinue or be nonadherent to [tyrosine kinase inhibitors]. Given the importance of these therapies for patients with CML, our data suggest a critical need to reduce patient costs for these therapies.”

Stacie B. Dusetzina, PhD, of The University of North Carolina at Chapel Hill, is the corresponding author for the Journal of Clinical Oncology article.

The study authors reported no potential conflicts of interest.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.