Pharmacoeconomic Evaluation of Hypomethylating Agents Used for the Treatment of MDS
Authors: Feinberg Bruce , Gilmore James , Haislip Sally , Franco Carlos M. , Gondesen Tom , Saleh Mansoor N. 
Published: April 2020

Abstract
Introduction. Supportive care has traditionally been the primary treatment for patients with MDS. The approval of hypomethylating agents provides therapeutic options for these patients. However more knowledge about the clinical benefits and associated economic implications in the community setting are required to understand how to best incorporate them into clinical guidelines and protocols. This pharmacoeconomic evaluation was conducted to address critical inputs for this medical decision making process.
Method. This evaluation is based on the retrospective analysis of medical and billing records for patients receiving treatment from January, 2006 to December, 2007, in the community setting. Only patients that received initial non-supportive care treatment with a hypomethylating agent decitabine (Dacogen (DAC)) or azacitidine (Vidaza (VID)) were included for this analysis. Due to the progressive nature of this disease, a longitudinal evaluation of the lines of therapy was conducted. Total costs per cycle were defined as the total costs associated with the utilization of hypomethylating agents, other downstream MDS treatments (eg lenalidomide), antiemetics, erythropoietins, WBC growth factors, and transfusions. The costs of antibiotics and antifungals were not included as the established treatment regimens were the same between the specified intervention protocols. The clinical response (CRp) based on available peripheral blood measures with a response being defined as Hgb ≥ 11 g/dL with no transfusions or erythropoietin use, ANC ≥ 1000/μL without the use of WBC growth factors, platelets ≥ 100,000/μL with no thrombopoietic agent, and no blasts for at least 4 weeks. The time to response and transfusion independence were determined by the individual cycles within the lines of therapy. The total and individual cost components were evaluated for each line of therapy based on the sequence of treatment received by cycles. The distribution of clinical response, transfusion independence, and other patient characteristics were analyzed using Chi-square tests and time to response and transfusion was compared using Kaplan-Meier methods. An incremental cost-effective ratio defined as the difference in cost between DAC and VID divided by the difference in CRp or time to response was calculated.
Results. A total of 70 patients received initial treatment with either DAC (40) or VID (30). Patients receiving DAC were treated a median of 2.5 cycles of initial treatment while those on VID were treated for a median of 3.5 cycles. No differences in baseline IPSS score were seen. Approximately 43% of those treated with Dacogen had a CRp compared to 13% of patients on VID (p=0.0095). The mean time to response was 105.8 and 130.9 days for DAC and VID, respectively (p=0.0018). The total costs from initial treatment to response were $16,679.19 and $13,954.33 for DAC and VID, respectively (p=0.47). Those with a CRp on DAC had a mean total cost of $34,435.62 compared to $36,852.57 with a CRp on VID with the number of cycles ranging from 2 to 13 for DAC and 8 to 9 for VID. However the mean total cost for those without a response to VID was $23,434.22 compared to $19,111.60 for those not responding to DAC. More patients receiving VID received other MDS agents after initial treatment than those receiving DAC, resulting in increased overall expenses over the remaining treatment period for these patients. The resulting incremental CE ratio based on CRp was $1336.60 per additional successfully treated patient while the incremental CE ratio using time to response was $108.56/day.
Discussion. Hypomethylating agents provide clinicians with necessary alternatives to traditional supportive care in the treatment of patients with MDS. Due to faster time to clinical response, Dacogen appears to have both a short- and long-term pharmacoeconomic advantage over Vidaza. Extended observation of patients and length of treatment is needed to understand the long-term ramifications for incorporation into clinical guidelines and protocols.