BACKGROUND: Imatinib (IM) has revolutionized the treatment of CML. The 5-year-survival rate of 89% for CML-CP and improving long-term tolerability profile made IM the first choice for CP-CML treatment. However, a subset of patients may become resistant or intolerant to IM. Two new tyrosine kinase inhibitors, nilotinib and dasatinib, have been developed to treat patients who become resistant or intolerant to IM. Complete cytogenetic response (CCyR) has been established as an effective measure for treatment efficacy. The objective of this study is to conduct an economic evaluation between nilotinib and dasatinib in the annual costs to achieve one CCyR in IM-resistant CML-CP patients from the Brazilian Public Healthcare System perspective (SUS).

METHODS: No head-head studies comparing nilotinib and dasatinib have been conducted. Data from dasatinib START-C study (

Blood 2007;109(10):4143
) were used to compare with the nilotinib phase II pivotal study CP arm. Patients with minimum 6 months follow up were included in this analysis and the median follow up between nilotinib and dasatinib was similar. However, the inclusion criteria for IM-intolerant patients differed between the studies, with IM-intolerant patients in the nilotinib study having more severe disease; patients had to have sustained, recurrent and persistent adverse events (AEs) and had no major cytogenetic response (MCyR) prior to study entry, whereas IM-intolerant patients could enter the dasatinib study with a MCyR and there was no strict duration of AEs specified. Therefore, in this analysis we focus on the comparison in IM-resistant patients. The CCR at minimum 6-month follow up for nilotinib vs. dasatinib in IM-resistant CML-CP patients was 31.4% vs. 22%. Number Needed to Treat (NNT) was calculated by the inverse of CCR. Annual costs were estimated on a 6 months AE treatment cost plus 1-year drug costs basis, assuming most of the management of AEs within the first 6 months. The costs of managing myelosuppression were included as AE costs. Other non-hematologic AEs (e.g. pleural effusion and bleeding) were excluded. Drug costs were based on IM 800 mg+5% premium ex-factory price for nilotinib and IM 600, 700 and 800 mg+5% for dasatinib.

RESULTS: The number of IM-resistant CML-CP patients needed to treat to achieve 1 CCR with nilotinib (NNT nilotinib = 3.18) is much lower than with dasatinib (NNT dasatinib= 4.55). To achieve each additional CCR, 1.37 more patients need to be treated for dasatinib than nilotinib. The cost to achieve 1 CCR in a 1-year period when the price is the same for both drugs (price=800mg IM +5%) is R$ 298,631 higher with dasatinib (R$ 941,595) than nilotinib (R$ 642,964). For dasatinib priced at 700mg and 600mg IM, the costs to achieve 1 CCR are respectively R$ 150,316 and R$ 44,376 higher than with nilotinib priced at 800mg + 5% IM.

CONCLUSIONS: The estimated costs to achieve 1 CCR in 1-year period with dasatinib is higher than with nilotinib for IM resistant CML-CP patients under the Brazilian Public Healthcare System. The inclusion of non-hematologic AEs would make nilotinib an even more cost saving alternative since nilotinib safety profile shows a much lower incidence in most of the non-hematologic AEs when compared to dasatinib. Longer follow up data are warranted to complement current analysis.

Topics:
cytogenetics, dasatinib, health care costs, imatinib mesylate, leukemia, myelocytic, chronic, nilotinib, follow-up, adverse event, complement system proteins, hemorrhage

Author notes

Disclosure:Employment: Market Access Manager. Consultancy: Health Economics Consultant.

2007, The American Society of Hematology
2007
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