Economic Burden of Adverse Events Among Patients with Chronic Myelogenous Leukemia Treated with BCR-ABL1 Tyrosine Kinase Inhibitors

Introduction: BCR-ABL1 tyrosine kinase inhibitors (TKIs) have been shown to be efficacious for the treatment of chronic myelogenous leukemia (CML); however, they have also been found to be associated with a number of clinically important adverse events (AEs). A recent study by Cortes et al. used the FDA Adverse Event Reporting System (FAERS) to identify potential AEs associated with treatment with imatinib, dasatinib and nilotinib (TKIs). The objective of our study was to assess healthcare costs associated with AEs identified in the FAERS study among TKI-treated patients irrespective of their causation.

Methods: Adult patients with at least 1 inpatient or ≥2 outpatient ICD-9-CM diagnosis codes for CML and at least 1 claim for a TKI treatment between 1/1/2006 and 9/30/2012 were identified from the Truven Health Analytics Commercial and Medicare MarketScan® research databases. The first claim for a TKI was designated as the index event. Patients were required to have continuous enrollment during 12-month periods before (baseline period) and after (follow-up period) the index event. Patients were also required to have no TKI treatment during the baseline period. Healthcare resource utilization (inpatient and outpatient) and costs associated with clinical events of interest were evaluated during the follow-up period. These events were selected from the AEs identified in the FAERS study based on the highest probability of association with a TKI and ability to translate the FAERS terms (MedDRA preferred terms) to healthcare claims terms.  The AEs included femoral arterial stenosis, intermittent claudication, peripheral arterial occlusive disease (PAOD), coronary artery stenosis, conjunctival hemorrhage, pleural effusion, malignant pleural effusion, and pericardial effusion. Inpatient or outpatient healthcare claims with primary ICD-9-CM diagnosis codes for the AEs were used in the analysis. A cause and effect relationship between AEs and treatment was not assessed.  

Results: The study sample included 2,005 CML patients receiving TKI therapy (mean age: 56 years; 56% male). Among all evaluated AEs, the highest mean inpatient healthcare costs were observed for femoral arterial stenosis ($16,800 per patient) and PAOD ($14,263 per patient), which had total mean medical costs (inpatient + outpatient) of $17,015 and $15,154 per patient, respectively. Mean outpatient healthcare costs were highest for coronary arterial stenosis ($1,861 per patient), followed by intermittent claudication ($947 per patient), PAOD ($891 per patient), and pleural effusion ($890 per patient). Mean total medical costs for fluid retention-related AEs, including pericardial effusion and pleural effusion, were $2,797 and $1,908 per patient, respectively. In this analysis, patients with conjunctival hemorrhage were found to have received treatment in outpatient setting only, with a mean total medical cost of $134 per patient. No patients with malignant pleural effusion were found in the study population.   

Conclusions: The healthcare costs of AEs identified in the FAERS as having the strongest association with TKI treatment are substantial. Vascular stenosis-related AEs, including femoral arterial stenosis and PAOD, appear to have the highest cost burden.

Table. AE Related Healthcare Costs among Study Population with CML
Adverse Event	Mean Inpatient Cost per Patient	Mean Outpatient Cost per Patient	Mean Total Medical Cost per Patient
Femoral Arterial Stenosis	$16,800	$215	$17,015
Peripheral Arterial Occlusive Disease (PAOD)	$14,263	$891	$15,154
Intermittent Claudication	$5,164	$947	$6,112
Coronary Arterial Stenosis	$3,083	$1,861	$4,944
Pericardial Effusion	$2,049	$748	$2,797
Pleural Effusion	$1,018	$890	$1,908
Conjunctival Hemorrhage	$0	$134	$134