Drug Utilization and Cost Considerations of Erythropoiesis-Stimulating Agents in Patients with Myelodysplastic Syndromes.
Authors: Laliberté François , McKenzie Scott R. , Bookhart Brahim K. , Duh Mei S. , Lefebvre Patrick 
Published: October 2019

Abstract
Background: Prevalent in the vast majority of patients at diagnosis, anemia associated with myelodysplastic syndromes (MDS) has historically been treated through red blood cell (RBC) transfusions. More recently, the erythropoiesis-stimulating agents (ESAs), epoetin alfa (EPO) and darbepoetin alfa (DARB), have also been employed for the treatment of MDS-associated anemia. To characterize real-world utilization of ESAs in adult patients with MDS, this retrospective analysis of medical claims examined EPO and DARB dosing patterns, ESA treatment costs, and RBC transfusion use.
Methods: An analysis of de-identified medical claims from January 2004–March 2006 using the Integrated Health Care Information Services (IHCIS) national database, which encompasses over 35 health plans, was conducted. Patients included were ≥18 years old, had ≥1 claim for MDS (ICD-9 code: 238.7) prior to ESA therapy, were newly initiated on either EPO or DARB, and received ≥2 doses during the treatment period. Patients with cancer (ICD-9 codes: 140–209) within 180 days prior to ESA treatment initiation were excluded. The study period terminated with either the last ESA treatment dose, end of data availability, initial AML diagnosis, or initial stem cell transplant, whichever occurred first. Dosing frequency was classified into mutually exclusive categories:
once weekly (QW; ≤9 days), once every two weeks (Q2W; 9.1 to 18 days), and once every three weeks or longer (≥Q3W; >18 days), based on the average dosing interval during treatment.
Mean cumulative ESA dose was used to calculate drug cost (based on July 2007 WAC: $12.005/1,000 Units for EPO and $4.576/mcg for DARB) and dose ratio (Units EPO: mcg DARB). RBC transfusions were identified from medical procedure codes, and the proportion of patients transfused during treatment was compared between the two groups.
Results: A total of 193 patients, 146 receiving EPO and 47 receiving DARB, formed the study population. Patients receiving EPO were older (69.9 vs. 66.2 years for DARB, p=0.018) with a similar proportion of women (56.2% vs. 51.1%, p=0.541). Extended dosing frequency (defined as every two weeks or greater, ≥Q2W) during treatment was observed in the majority of patients in both groups (EPO: QW 43%, Q2W 35%, ≥Q3W 22%; DARB: QW 15%, Q2W 60%, ≥Q3W 25%). Mean treatment duration was similar for both groups (EPO: 88.3 days; DARB: 87.1 days; p=0.944). The mean cumulative ESA dose administered was 406,685 Units for the EPO group and 1,509 mcg for the DARB group, corresponding to a dose ratio of 270:1 (Units EPO: mcg DARB). Use of concurrent white blood cell growth factors (G-CSF or GM-CSF) was similar (EPO 8.2%, DARB 6.4%, p =0.683). RBC transfusion was administered to 8.9% of EPO patients compared to 8.5% of DARB patients (p=0.934) Cumulative drug cost was lower in the EPO group by $2,022 (EPO $4,882; DARB $6,904; p=0.101) compared to DARB.
Conclusion: Based on these data from actual clinical practice, the majority of MDS patients received extended dosing regimens (≥Q2W) of either EPO or DARB. A dose ratio of 270:1 (Units EPO: mcg DARB) between the two agents and 29% lower drug cost in the EPO group was observed. These findings are similar to those previously reported from published real-world ESA drug utilization studies in other therapeutic areas.