Comparative efficacy, safety, and cost of iron chelation monotherapy vs. combination therapy in pediatric beta-thalassemia major: a single-center retrospective study

  • Dewi Sharon Simorangkir
  • Nafrialdi Nafrialdi Department of Pharmacology and Therapeutics, Faculty of Medicine, Universitas Indonesia
  • Pustika Amalia Wahidiyat Department of Child Health, Faculty of Medicine, Universitas Indonesia
  • Vivian Soetikno Department of Pharmacology and Therapeutics, Faculty of Medicine, Universitas Indonesia
Keywords: thalassemia; children; iron overload; chelation agents; cost

Abstract

Background Iron chelation therapy is used to maintain iron balance in β-thalassemia major patients who undergo repeated blood transfusions.

Objective To compare the efficacy, safety, and cost of iron chelation combination regimens [deferiprone (DFP) + deferoxamine (DFO) or DFP + deferasirox (DFX])] vs. high-dose DFP monotherapy (≥ 90 mg/kg/day) in pediatric β-thalassemia major patients.

Methods This cross-sectional, retrospective study was done at Cipto Mangunkusumo Hospital, Jakarta, Indonesia. Retrospective data was obtained from electronic medical records of pediatric b-thalassemia major patients with serum ferritin of ≥ 2,500 ng/mL and/or transferrin saturation of ≥ 60%, who received either combination or monotherapy iron chelation agents. Outcome effectiveness was determined by the reduction of serum ferritin level of at least 80%. Safety was analyzed descriptively. A pharmacoeconomic analysis was performed based on clinical outcomes consisting of effectiveness and direct medical costs.

Results At the end of the study, serum ferritin was reduced in 34.7% of the combination therapy group and 27.5% of the monotherapy group, however there was no significant difference between the two treatments (P=0.391). Nine (19.5%) patients on combination therapy and 17 (21.2%) patients on monotherapy had adverse drug reaction (ADR), with the most frequently reported ADR was elevated transaminase enzyme levels. Cost minimization analysis revealed that monotherapy for 6 months was IDR 13,556,592.64 less expensive than combination therapy (IDR 44,498,732.07); whereas monotherapy for 12 months was IDR 20,162,836.10 less expensive than combination therapy (IDR 78,877,661.12).

Conclusion Combination regimens are as effective as monotherapy regimens in reducing serum ferritin in pediatric β-thalassemia major patients. There is no differences of ADR between combination or monotherapy. The average cost per patient is less expensive with monotherapy compared to combination therapy.

References

1. Direktorat Pencegahan dan Pengendalian Penyakit Tidak Menular, Direktorat Jenderal Pencegahan dan Pengendalian Penyakit, Kementrian Kesehatan Republik Indonesia. Thalassemia. [cited 2018 April 4]. Available from: http://p2ptm.kemkes.go.id/informasi-p2ptm/thalassemia.
2. Unit kerja kelompok hematologi-onkologi Ikatan Dokter Anak Indonesia (power point slides) 2019 Mar 19 [cited 2019 Mar 19].
3. Gatot D, Amalia P, Sari TT, Chozie NA. Pendekatan mutakhir kelasi besi pada thalassemia. Sari Pediatri. 2007;8:78–84.
4. Trinchero A, Marchetti M, Giaccherini C, Tartari CJ, Russo L, Falanga A. Platelet haemostatic properties in ?-thalassaemia: the effect of blood transfusion. Blood Transfus. 2017;15:413?21. DOI: 10.2450/2016.0033-16.
5. Karami H, Kosaryan M, Amree AH, Darvishi-Khezri H, Mousavi M. Combination iron chelation therapy with deferiprone and deferasirox in iron-overloaded patients with transfusion-dependent ?-thalassemia major. Clin Pract. 2017;7:912. DOI: 10.4081/cp.2017.912.
6. Gomber S, Jain P, Sharma S, Narang M. Comparative efficacy and safety of oral iron chelators and their novel combination in children with thalassemia. Indian Pediatr. 2016;53:207?10. DOI: 10.1007/s13312-016-0821-4.
7. Tanner MA, Galanello R, Dessi C, Smith GC, Westwood MA, Agus A, et al. Combined chelation therapy in thalassemia major for the treatment of severe myocardial siderosis with left ventricular dysfunction. J Cardiovasc Magn Reson. 2008;10:12. DOI: 10.1186/1532-429X-10-12.
8. Elalfy MS, Adly AM, Wali Y, Tony S, Samir A, Elhenawy YI. Efficacy and safety of a novel combination of two oral chelators deferasirox/deferiprone over deferoxamine/deferiprone in severely iron overloaded young beta thalassemia major patients. Eur J Haematol. 2015;95:411?20. DOI: 10.1111/ejh.12507.
9. Wang W, Knovich MA, Coffman LG, Torti FM, Torti SV. Serum ferritin: Past, present and future. Biochim Biophys Acta. 2010;1800:760-9. DOI: 10.1016/j.bbagen.2010.03.011.
10. Totadri S, Bansal D, Bhatia P, Attri SV, Trehan A, Marwaha RK. The deferiprone and deferasirox combination is efficacious in iron overloaded patients with ?-thalassemia major: a prospective, single center, open-label study. Pediatr Blood Cancer. 2015;62:1592?6. DOI: 10.1016/j.bbagen.2010.03.011.
11. Pennell DJ, Berdoukas V, Karagiorga M, Ladis V, Piga A, Aessopos A, et al. Randomized controlled trial of deferiprone or deferoxamine in beta-thalassemia major patients with asymptomatic myocardial siderosis. Blood. 2006;107:3738-44. DOI: 10.1182/blood-2005-07-2948.
12. Taher A, Sheikh-Taha M, Sharara A, Inati A, Koussa S, Ellis G, et al. Safety and effectiveness of 100 mg/kg/day deferiprone in patients with thalassemia major: a two-year study. Acta Haematol. 2005;114:146-9. DOI: 10.1159/000087888.
13. Chairunissa HG, Sauriasari R, Rizkyani NA. Cost-effectiveness analysis of deferoprone and deferasirox on thalassemia-major patients in Tangerang District Hospital, Indonesia. J Young Pharm. 2018;10:s128–31. DOI:10.5530/jyp.2018.2s.26.
14. Xia S, Zhang W, Huang L, Jiang H. Comparative efficacy and safety of deferoxamine, deferiprone and deferasirox on severe thalassemia: a meta-analysis of 16 randomized controlled trials. PLoS One. 2013;8:e82662. DOI:10.1371/journal.pone.0082662.
15. Pepe A, Rossi G, Bentley A, Putti MC, Frizziero L, D’Ascola DG, et al. Cost-utility analysis of three iron chelators used in monotherapy for the treatment of chronic iron overload in B-thalassaemia major patients: an Italian perspective. Clin Drug Investig. 2017;37:453–64. DOI: 10.1007/s40261-017-0496-1.
Published
2022-03-04
How to Cite
1.
Simorangkir D, Nafrialdi N, Wahidiyat P, Soetikno V. Comparative efficacy, safety, and cost of iron chelation monotherapy vs. combination therapy in pediatric beta-thalassemia major: a single-center retrospective study. PI [Internet]. 4Mar.2022 [cited 28May2024];62(2):91-. Available from: https://paediatricaindonesiana.org/index.php/paediatrica-indonesiana/article/view/2556
Section
Pediatric Hemato-Oncology
Received 2020-12-07
Accepted 2022-03-04
Published 2022-03-04