Financial Impact of Imatinib Discontinuation in Brazil - a Pharmoeconomic Study
Authors: Centrone Renato Torrescasana , Bonafe Isabel , Miranda Eliana C , Seguro Fernanda S , Magalhaes Gustavo HR , Clementino Nelma D , Moellmann-Coelho Arthur , Luise Ingrid , Conchon Monika , Gonçalves Natália N , Bortolini Jaisson , Fogliatto Laura Maria , Souza Carmino Antonio , Pagnano Katia B , Bendit Israel 
Published: November 2019

Quantitative RT-PCR (RQ-PCR) is an essential test for BCR-ABL transcripts monitoring in patients with chronic myeloid leukemia (CML) treated with tyrosine kinase inhibitors (TKI), to guide therapy and for monitoring after a discontinuation attempt in patients with deep molecular response. RT-PCR (RQ-PCR) is currently not reimbursed by the public health system in Brazil.
Aims: To assess the proportion of CML patients treated with first-line imatinib eligible for discontinuation, and to calculate the financial impact resulting from IM discontinuation.
Methods: Between January 2010 and December 2011, 151 consecutive cases of chronic phase myeloid leukemia treated with Glivec first-line therapy were evaluated. Between June and December 2013 there was a switch in treatment from Glivec to generic IM. Cases that exhibited stable MR4.5 for 2 years with first-line IM were selected for the study. Cases which switched treatment to second-generation inhibitors and patients older than 75 years of age were excluded from the study. The methodology used was a pharmacoeconomic cost-utility analysis. Glivec monthly cost has been estimated at U$ 3,257.54 and the generic IM U$ 365.48, while the unitary value for the PCR test was U$ 117.49. In order to calculate the period of IM consumption, the median age of the patients and the life expectancy data released in 2015 by the Brazilian Institute of Geography and Statistics (IBGE) of 75 years was considered. In the first analysis, the life expectancy for the sample group, and the total cost of treatment (cost of Glivec, generic IM and four annual RQ-PCR tests for each patient) were calculated. The second analysis consisted of a hypothetical calculation of costs under the scenario where the study group is therapy-free (estimating that the survival rate under discontinued therapy was similar to data available in the literature, with discontinuation success of 50% in this group) with molecular monitoring by PCR monthly in the first year, bimestrial in the second year and every three months from the third year on.
Results: One hundred fifty-one cases were analyzed, with a median age at diagnosis of 45. From those, 56 (37%) patients achieved stable MR4.5 with a median time to achieve MR4.5 of 71 months. The median duration of follow-up was 8 (0-10) years. In the last follow-up, 108 patients were still in treatment, 10% (11/108) with Glivec, 90% (97/108) on generic IM. Patients excluded from the analysis: 4 cases aged more than 75 years; 13 that switched therapy to another TKI and one during the bone marrow transplant period. Finally, 38/56 (25%) patients who obtained MR4.5 with IM were eligible for analysis.
Analysis 1: Total treatment cost for the 38 eligible cases, if the individuals sustained continuous use of IM, considering the life expectancy of 75 years. The calculations resulted in an average of 29 years of treatment, with an estimated cost of U$ 9,363,866.00.
Analysis 2: The cost after discontinuation of generic IM, estimating that 50% of patients would resume the treatment. Nineteen cases were analyzed. The costs related to the monthly PCR exam in year 1, bimestrial exam in year 2 and trimester in year 3, until the patient reaches 75 years of age, have been calculated, with a total cost of U$ 7,823.515.
Conclusions: The economy resulting from the discontinuation of treatment (US$1.540.340,00) by 19 patients could support 219 patients tests over 29 years, or 12.110 tests each year. This data is relevant, providing that RQ-PCR is essential for the appropriate management of CML and to allow safe discontinuation of the therapy in eligible patients. Such results may help to change the current health policies concerning RQ-PCR tests reimbursement for CML management and future attempting of TFR in Brazil.

Disclosures
Centrone: Novartis: Honoraria; Janssen: Honoraria. Magalhaes:Novartis: Honoraria. Pagnano:Pint Pharma: Consultancy; Abbvie: Consultancy; Sandoz: Consultancy.