Cost-effectiveness of Imatinib versus Interferon-α in the Treatment of Patients Newly Diagnosed With Chronic Myeloid Leukemia, Under the Brazilian Public Healthcare System PerspectiveFábio Mataveli, MD,MBA1*, Alessandra Calabró, MBA2*, Wellington Mendes, MD2*, Denizar Vianna, MD,PhD3*, Pedro Dorlhiac-Llacer, MD,PhD4*, Ricardo Bigni, MD,PhD5, and Vania Hungria, MD,PhD6.1Internal Medicine, Federal University of São Paulo, São Paulo, SP, Brazil; 2Novartis Biociências S.A., São Paulo, SP, Brazil; 3Internal Medicine, State University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil; 4Fundação Pró-Sangue, State University of São Paulo, São Paulo, SP, Brazil; 5Hematology, National Institute of Cancer, Rio de Janeiro, RJ, Brazil and 6Hematology, Santa Casa de São Paulo, São Paulo, SP, Brazil.

BACKGROUNDThe 60-month follow-up data for patients randomized to imatinib in the InternationalRandomized Interferon vs STI571 Study (IRIS) demonstrated significant clinicalimprovements in survival rates and QALYs gained (17,09 years; 13,58 QALYs) inpatients newly diagnosed with chronic myeloid leukemia (CML) and treated withimatinib in comparison to patients under interferon-alpha (INF-α) (9,10 years; 6,31QALYS) as first line therapy (Table 1)1. Although reimbursed as second line therapy for chronic phase CML patients who did not respond to INF-α, imatinib wasnot considered for public reimbursement as first line treatment in Brazil basedsolely on drug costs. An economic evaluation of imatinib as first line treatment versus INF-α was performed under the Brazilian Public Healthcare System perspective, according to the long-term follow-up data from IRIS, literature recommendations and prior health technology assessment from the NationalInstitute for Clinical Excellence (NICE) to consider long term follow-up survival andadverse events costs2,3.

OBJECTIVEEvaluate the cost-effectiveness of imatinib compared with IFN-α for first-line treatment ofchronic myeloid leukemia under the Brazilian public healthcare system perspective.

METHODS For the economic model, a base case of 100 patients for each treatment option wasconstructed focused on drug costs, adverse events and utilities values from the IRISstudy for both groups (Table 1 and 2). Drug costs were estimated based on theBrazilian public healthcare reimbursement payment (APAC-SUS) for chronic phase CMLtreatment. Febrile neutropenia (grade III and IV), depression, nausea and abnormal liver-function results were considered as adverse events. Clinical guidelines andprotocols from two public hematology Brazilian centers, Fundação Pró-Sangue FM-USPand Instituto Nacional do Cancer, were used to estimate adverse events treatmentcosts. Adverse events frequency for all grades was based on data published by NICEand the Agency for Health Care Research and Quality2,3. Due to the high crossover ratefrom INF-α to Imatinib group observed in the IRIS study (64.9% from INF-α to imatinibafter a median follow-up of 60 months) the estimated life time survival for INF-αtreatment group was based on the European Study Group on Interferon in ChronicMyeloid Leukemia4,5. Annual discount rates were of 6% for costs and 1.5% for QALYs.

CONCLUSIONS•Assuming a conservative cost-effectiveness threshold of less than US$ 25,500, which

is three times the GDP per capita in Brazil (US$ 8,500 in 2005), the ICER for imatinibcompared with INF-α falls within the range considered by the World Heath Organizationas a cost-effective fist line treatment for patients newly diagnosed with CML6.

•Adoption of Gleevec as first line therapy in the treatment of chronic phase CML wouldimmediately benefit patients that are still under INF-α therapy.

References1. B. J. Druker, F. Guilhot, S. O’Brien, R. A. Larson, N. Journal of Clinical Oncology,

2006 ASCO Annual Meeting Proceedings Part I. Vol 24, No. 18S (June 20Supplement), 2006: 6506

2. Health Technology Assessment 2004; Vol. 8: No. 28.

3. Agency for Healthcare Research and Quality (AHRQ). Report on the relative efficacy oforal cancer therapy for medicare beneficiares versus currently covered therapy.Imatinib for Chronic Myeloid Leukemia. November, 2005.

4. O’Brien SG, Guilhot F, Larson RA, et al. Imatinib compared with interferon and low-dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukaemia. N Engl J Med. 2003;348:994-1004.

5. Bonifazi F, de Vivo A, Rosti G, et al. Chronic myeloid leukemia and interferon-alpha: astudy of complete cytogenetic responders. Blood. 2001;98:3074-3081.

6. WHO Commission. Macroeconomics and health: investing in health for economicdevelopment. Geneva: World Health Organization; 2002

0 50 100 150 US$

Gleevec US$ 76,684

INF-a US$ 140,604

Table 1. Outcomes per patient

Outcome Per Patient Gleevec INF-α

Life Years Saved* 17.09 9.1 7.99

Discounted Life Years saved 14.52 8.22 6.3

QALYs saved 13.58 6.31 7.27

Discounted QALY’s saved 11.57 5.7 5.87

*discount rate: 1.5% per year

Table 2. Base-case model results

Costs(US$)* Drug Therapy Gleevec INF-α

Average patient cost/year 21,405 13,345 8,060

Lifetime cost ** 193,023 81,813 111,210

Adverse Events per 100 patients/yr

Depression 1,634 6,301 (4,667)

Neutropenia 72,724 127,140 (54,416)

Abnormal Liver Function tests 2,274 3,914 (1,640)

Nausea 50 3,249 (3,199)

Total AE Cohort Cost per year 76,684 140,604 (63,920)

Total Lifetime Cost per patient 199,938 90,538 109,400

*1 US$=R$ 2.28

**discount rate: 6% per year

RESULTS•The annual average costs for the treatment of adverse effects in the INF-α were almost

twice (1.83) as that for the imatinib group. Adverse events lifetime costs for INF-α were24% higher than imatinib, even though imatinib granted a projected 6.3 years survivaladvantage over INF-α (Figure 1).

Figure 1. Adverse Events Management Average Annual Cost (100 patients cohort)

DRUG

•The resulting incremental cost-effectiveness ratio (ICER) of imatinib, compared to IFN-α, considering adverse events was US$ 18,637 per QALY gained (Table 3 andTable 4).

Table 3. Incremental Cost-Effectiveness Ratio (ICER)

Drug Gleeve INF-α

Total Lifetime Cost per patient (US$) 199,938 90,538 109,400

Discounted QALYs 11.57 5.7 5.87

Incremental Cost Effectiveness Ratio US$ 18,637

*1 US$=R$ 2.28

**discount rate: 6% per year

Table 4. Values used to calculate the Incremental Cost-effectiveness Ratio(ICER). Discount rates; 1.5% per year on QALYs and Life Years; 6% peryear on costs.

Drug Survival Annual Lifetime QALY Cost per Incremental(years) Average Costs saved QALY cost-

Costs (US$) effectiveness (US$) ratio (US$)

INF-a 8,22 14,751 90,538 5,70 15,884

Gleevec 14,52 24,365 199,938 11,57 17,281 18,637 per QALY