1.
Efficacy of Deferasirox for the treatment of iron overload in Chinese thalassaemia major patients: results from a prospective, open-label, multicentre clinical trial
Lai YR, Liu RR, Li CF, Huang SL, Li Q, Habr D, Martin N, Shen ZX
Transfusion Medicine. 2013;23((6):):389-96.
Abstract
OBJECTIVE To assess the efficacy and safety of deferasirox in Chinese thalassaemia major (TM) patients BACKGROUND EPIC (Evaluation of Patients' Iron Chelation with Exjade() ) was a large multi-national study and, notably, the first clinical trial of an iron chelator registered with the Chinese State Food and Drug Administration. METHODS Efficacy and safety of deferasirox were compared in Chinese (n=117) and non-Chinese (n=998) TM patients. Deferasirox was initiated at 20mgkg(-1) day(-1) , with titration increments of 5-10 mgkg(-1) day(-1) , based on serum ferritin trends and safety parameters. RESULTS At baseline, Chinese patients were younger than non-Chinese (mean age 6.8 versus 19.5years), with higher median serum ferritin (4519 vs 3058ngmL(-1) ). Over 1year, mean actual deferasirox dose was similar for Chinese and non-Chinese patients (24.6 and 24.0mgkg(-1) day(-1) , respectively); median serum ferritin did not change significantly from baseline in Chinese patients (+340ngmL(-1) , P=0.102) and significantly decreased in non-Chinese patients (-220ngmL(-1) ; P<0.001). In the 1-year extension in Chinese patients, (mean actual deferasirox dose 33.6mgkg(-1) day(-1) ), median serum ferritin decreased (-756ngmL(-1) ; P = 0.0397), with a numerically higher reduction in patients aged >=6 to <12 than <6years (-982 vs -457ngmL(-1) , respectively). The safety profile of deferasirox in Chinese patients was similar to the overall population with respect to clinically-relevant findings. CONCLUSION Age and deferasirox exposure influenced study findings, supporting the need for longer-term treatment and dose escalation to >=30mgkg(-1) day(-1) to achieve neutral or negative iron balance in heavily iron overloaded and younger Chinese patients. 2013 The Authors. Transfusion Medicine 2013 British Blood Transfusion Society.
2.
Curative effects and safety of deferasirox in treatment of iron overload in children with beta-thalassemia major Chinese
Gao HY, Li Q, Chen JJ, Chen GF, Li CG
Zhongguo Dang Dai Er Ke Za Zhi [Chinese Journal of Contemporary Pediatrics]. 2011;13((7):):531-4.
Abstract
OBJECTIVE To study the effectiveness and safety of deferasirox (DFX) in the treatment of iron overload in children with beta-thalassemia major. METHODS Twenty-four beta-thalassemia major children with iron overload who received regular blood transfusion were randomly enrolled. The serum feritin (SF) levels were measured in the patients after different doses of DFX treatment. The DFX treatment-related adverse events were observed. The values of cardiac MRI T2* and liver MRI T2* were compared between the patients receiving DFX treatment for 5 years and the patients treated with deferoxamine and deferiprone. RESULTS The patients with iron overload did not respond to DFX at the initial dose of 20-30 mg/kg?d. However, the SF level decreased significantly after the dose of DFX increased to 30-40 mg/kg?d (U=58, P<0.01). Serum liver transaminase elevation was the most common adverse effect, followed by non-progressive elevation in serum creatinine level. The mean SF level was significantly lower (1748±481 ng/mL vs 3462±1744 ng/mL; P<0.05), in contrast, the liver MRI T2* value was significantly higher (8.5±2.9 ms vs 2.7±1.9 ms; P<0.01) in patients receiving DFX treatment for 5 years than in the controls. There were no significant differences in the cardiac MRI T2* value between the two groups. CONCLUSIONS DFX can reduce SF levels in a dose-dependent manner in children with beta-thalassemia major. It can significantly lower liver iron overload but not cardiac overload. Serum liver transaminase elevation and non-progressive elevation in serum creatinine level are major adverse effects in DFX treatment.
3.
Cost effectiveness of deferasirox compared to desferrioxamine in the treatment of iron overload in lower-risk, transfusion-dependent myelodysplastic syndrome patients
Tolley K, Oliver N, Miranda E, Migliaccio-Walle K, Bozkaya D, Li Q
Journal of Medical Economics. 2010;13((3):):559-70.
Abstract
Objective: The study evaluated the cost effectiveness of deferasirox (Exjade) compared to non-proprietary desferrioxamine (DFO) for the control of transfusional iron overload in lower risk myelodysplastic syndromes (MDS) patients. A UK National Health Service perspective was adopted. Methods: Recent clinical evidence has demonstrated the efficacy and safety of deferasirox in transfusion-dependent MDS patients with elevated serum ferritin levels. An economic model was used to extrapolate the clinical benefits of iron chelation therapy (ICT) in a cohort of lower risk MDS patients. Costs for drug acquisition, drug administration and monitoring, and quality of life (utility) outcomes associated with mode of drug administration were derived from a variety of sources. The incremental cost per QALY gained for deferasirox was estimated. Costs and outcomes were discounted at 3.5% in line with UK standards. Results: The base-case cost effectiveness of deferasirox versus DFO was estimated to be 20,822 per QALY gained, the key driver being the additional quality of life benefits associated with a simpler mode of administration for deferasirox. A mean survival benefit for both forms of ICT of 4.5 years was estimated. The results were sensitive to drug dose, days of DFO administration, and patient weight. Conclusions: In the UK, a cost per QALY below 20,000-30,000 is considered cost effective. Hence, the results from this economic analysis suggest deferasirox is cost effective in lower risk, transfusion-dependent, MDS patients. Limitations with the analysis include a lack of comparative randomised controlled trial evidence, in particular to differentiate survival and clinical outcomes for deferasirox and DFO.