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Cost-Effectiveness of Interferon-α and Conventional Chemotherapy in Chronic Myelogenous Leukemia

Michael W. Kattan, PhD; Yuji Inoue, MD; Francis J. Giles, MD; Moshe Talpaz, MD; Howard Ozer, MD, PhD; Francois Guilhot, MD; Eliana Zuffa, MD; Stephen L. Huber, MS; and J. Robert Beck, MD
[+] Article and Author Information

For author affiliations and current author addresses, see end of text. Acknowledgments: The authors thank Irene Albright and Linda Higgins for editorial assistance. Grant Support: By grants LM04905 and LM07093 from the National Institutes of Health, by Association pour la Recherche Contre le Cancer and Foundation Centre la Leucemie, and by a grant from the Schering-Plough Corp. Requests for Reprints: J. Robert Beck, MD, Information Technology Program, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030. Current Author Addresses: Drs. Kattan and Beck: Information Technology Program, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030.


Copyright ©2004 by the American College of Physicians


Ann Intern Med. 1996;125(7):541-548. doi:10.7326/0003-4819-125-7-199610010-00002
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Objective: To compare the cost-effectiveness of interferon-α with that of hydroxyurea as initial therapy for patients with chronic myelogenous leukemia (CML) in the chronic phase.

Design: A decision analysis and Markov model that described the natural history of the therapeutic process. The Markov model contained two treatment arms (interferon-α and hydroxyurea) and eight states of health (complete hematologic remission with cytogenetic response, complete hematologic remission without cytogenetic response, partial hematologic remission, chronic phase without hematologic remission, accelerated phase, blast crisis, bone marrow transplantation, and death). Probabilities, costs, and utilities were obtained from published clinical studies and clinical investigators.

Measurement: Quality-adjusted years of life saved and costs and qualities discounted at 5% per year.

Setting: University medical centers in North America and Europe.

Patients: Meta-analysis of results from patients studied in clinical trials.

Results: The model's predictions of median survival (69 months with interferon-α therapy and 58 months with hydroxyurea therapy) were derived from data in the recent literature. In patients 50 years of age, interferon-α improved life expectancy over hydroxyurea by approximately 18 months. The marginal cost-effectiveness of interferon-α (incremental discounted cost of interferon-α compared with that of conventional therapy) was $34 800 per quality-adjusted year of life saved. The model was sensitive to the monthly cost of interferon-α therapy (if the cost of interferon-α is reduced by one third, the cost-effectiveness becomes $19 300 per quality-adjusted year of life saved) but was not particularly sensitive to the costs associated with blast crisis or bone marrow transplantation. The other significant variable was quality of life during therapy with interferon-α; when this measure was varied from 70% to 100% of the quality of life during hydroxyurea therapy, cost-effectiveness changed from $123 200 to $25 620 per quality-adjusted year of life saved. When the quality of life associated with interferon-α was less than 62% of the quality of life associated with hydroxyurea, the discounted quality-adjusted life expectancy with interferon-α was less than that with hydroxyurea.

Conclusion: Compared with hydroxyurea, interferon-α is, in most clinical scenarios, a cost-effective initial therapy for patients with chronic-phase CML who can tolerate the drug.

Figures

Grahic Jump Location
Figure 1. Square nodes represent choices, and circular nodes represent chance outcomes. ACCEL = accelerated-phase chronic myeloid leukemia; BLAST = blast crisis; BMT = bone marrow transplantation; DEAD = death from chronic myeloid leukemia; CHR = complete hematologic remission; CHRKR = complete hematologic remission with karyotypic response; CHRONIC = chronic-phase chronic myeloid leukemia; HU = hydroxyurea therapy; IFN = interferon-α therapy; PHR = partial hematologic remission.
Decision tree for first 8 months of therapy.
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Grahic Jump Location
Figure 2. Arrows represent possible transitions in the model. A curved arrow pointing to the same node from which it originates indicates that a patient may remain in that node for more than one cycle (month). ACCEL = accelerated-phase chronic myeloid leukemia; BLAST = blast crisis; BMT = bone marrow transplantation; DEAD = death from chronic myeloid leukemia; CHR = complete hematologic remission; CHRKR = complete hematologic remission with karyotypic response; CHRONIC = chronic-phase chronic myeloid leukemia; PHR = partial hematologic remission.
State-transition diagram of Markov model for chronic myeloid leukemia.
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Grahic Jump Location
Figure 3. Patients receiving interferon-α or hydroxyurea (HU) begin in Markov models during month 9 of therapy. Interferon-α recipients who show toxicity (Tox) at any time between months 9 and 24 switch to hydroxyurea. After month 24, patients without karyotypic response also switch to hydroxyurea. * = Only patients who can tolerate interferon-α and have a karyotypic response at this point continue to receive interferon-α.
Transitions in the Markov model caused by intolerance of interferon-α (IFN) or lack of karyotypic response (KR).
Grahic Jump Location
Grahic Jump Location
Figure 4. Effect of patient age at diagnosis on marginal cost-effectiveness of interferon-α. Baseline quality adjustments and baseline costs were used. Effect of the monthly cost of interferon-α on the marginal cost-effectiveness of the drug. Baseline quality adjustments were used. Effect of the quality of life during interferon-α treatment on the marginal cost-effectiveness of the drug. Baseline costs were used. A quality-of-life modifier of 1 indicates that interferon-α therapy has no disutility.
Top.Middle.Bottom.
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