Comparative Cost-Effectiveness of Azacitidine Versus Decitabine for the Treatment of Myelodysplastic Syndromes (MDS).

National Comprehensive Cancer Network guidelines recommend the use of azacitidine and decitabine to treat patients with myelodysplastic syndromes (MDS). In a Phase III clinical trial (AZA-001), MDS patients treated with azacitidine experienced a statistically significant increase in overall survival compared to patients receiving conventional care (24.5 vs. 15.0 months, p<0.0001) (Fenaux 2009). In addition, fewer azacitidine-treated patients required blood transfusions, and use of azacitidine delayed progression to acute myelogenous leukemia (AML). While the clinical benefits of azacitidine have been demonstrated, no study has evaluated its cost-effectiveness relative to decitabine.

We developed a dynamic decision-analytic model (Markov process with 1-month cycles) to evaluate the cost-effectiveness of azacitidine versus decitabine for the treatment of MDS patients. Model parameters were derived from published literature, product labels, clinical trial data, and drug pricing and medical services cost databases. While patient populations in the clinical trials referenced for this model differed (i.e., approximately 1/3 of patients in the decitabine clinical trial were classified as lower-risk MDS patients, whereas approximately 90% of the azacitidine trial patients were higher-risk) (Kantarjian 2006, Fenaux 2009), data from the two trials were the highest quality available. The model tracks hypothetical cohorts of 1,000 MDS patients treated with azacitidine or decitabine over time periods of 1 and 3 years. Patients either remain in or transition among 4 health states in the model: (1) MDS with transfusion dependence; (2) MDS with transfusion independence; (3) progression to AML; or (4) dead. Clinical and economic consequences of adverse events were not included in the model. Clinical outputs generated by the model include: (1) number of patients progressing to AML; (2) number of patient months with transfusion independence; and (3) quality-adjusted life months/years (QALMs/QALYs). The primary economic output was treatment cost (including drug acquisition, administration and monitoring, blood transfusions, and iron chelation therapy). Cost-effectiveness of azacitidine versus decitabine was measured incrementally as: (1) cost per QALY gained; (2) cost per additional patient month of transfusion independence; (3) cost per additional case of AML progression avoided. The model used a US third-party payer perspective. Costs are stated as 2009 US dollars. One-way sensitivity analyses were performed on key model parameters to assess robustness of results.

The total number of QALYs (per 1,000 patients) for azacitidine-treated patients exceeded those for decitabine-treated patients in both the 1-year scenario (579 vs. 526) and the 3-year scenario (1,446 vs. 1,175). The total number of patient months with transfusion independence was higher for azacitidine vs. decitabine in both the 1-year scenario (4,340 vs. 3,521) and the 3-year scenario (11,836 vs. 8,553). A greater number of azacitidine-treated patients avoided progression to AML compared to decitabine-treated patients in both the 1-year scenario (664 vs. 462) and the 3-year scenario (372 vs. 231). Total per-patient costs for azacitidine-treated patients were lower than for decitabine-treated patients in both the 1-year scenario ($29,921 vs. $43,208), and the 3-year scenario ($101,052 vs. $106,806). In the 1-year scenario, costs for an azacitidine-treated patient were $13,287 less than those for a decitabine-treated patient, and azacitidine conferred a benefit of 0.0526 additional QALYs. In the 3-year scenario, costs for an azacitidine-treated patient were $5,754 less than those for a decitabine-treated patient, and azacitidine conferred a benefit of 0.2707 additional QALYs. Thus, incremental cost-effectiveness ratios (ICERs) for both the 1-year and 3-year scenarios demonstrate that azacitidine consistently had lower cost and provided greater health benefit compared to decitabine across all outcomes of interest.

Model results suggest that despite a higher-risk profile in the underlying data for azacitidine, treatment of MDS patients with azacitidine leads to cost savings—it costs less and confers greater clinical benefit than decitabine. These results accentuate azacitidine as a major asset in providing cost-effective care for MDS patients.

Miller: Celgene Corporation: Consultancy. Fenaux: Celgene, Ortho Biotech, Roche, Novartis, Cephalon, Epicept, Amgen, Merck: Honoraria, Research Funding. Beach: Celgene Corporation: Employment. Gidwani: Celgene Corporation: Consultancy. Khan: Celgene Corporation: Employment.