소아 환자에서 deferoxamine에서 deferasirox로 변경 이후 efficacy와 safety 평가
Evaluation of the efficacy and safety of deferasirox in pediatric patients who changed iron chelating agent from deferoxamine to deferasirox
0
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Deferoxamine has for decades been the standard for iron chelation therapy, but requires administration as a slow continuous subcutaneous or intravenous infusions five to seven times per week, potentially leading to poor compliance, reduced effectiveness. Deferasirox was developed in response to the need for an oral iron chelating agent. Its convenient, once-daily,oral administration schedule offers the potential to improve compliance. However, long-term efficacy and safety remain to be established. This study evaluated the efficacy and safety of deferasirox in pediatric patients who were switched off deferoxamine iron chelating therapy and introduced to deferasirox. It was conducted by method of retrospective chart review. Patients were divided into two groups. Group A(n=22)was constituted of patients who were converted from deferoxamine to deferasirox for their iron chelating therapy. Group B(n=24) was constituted of patients starting iron chelating therapy directly on deferasirox and had never changed. We evaluated the efficacy and the safety of deferasirox through intra-group and inter-group comparisons. The patients in group A, those who were administered deferoxamine, showed a trend of decrease in ferritin levels one month after administration(-222±117.16 ng/ml, p=0.845). In contrast, when the same patients changed their chelating agent to deferasirox, there was a tendency for ferritin levels to increase(+40.67±965.5 ng/ml, p=0.384). However, the ferritin level drop was not statistically different between the drugs (p=0.422). The use of deferasirox in group B decreased ferritin levels more than any other group, but was not statistically significant(-701.5±1687.5 ng/ml, p=0.053). Adverse events were more frequently observed with deferasirox than with deferoxamine in group A(59.1% vs 27.3%). The most common adverse events with deferasirox were gastrointestinal problems and LFT abnormality. On the other hand, skin problems were the most frequent adverse reactions to deferoxamine. Deferasirox showed similar efficacy to deferoxamine in terms of decreasing ferritin levels in pediatric patients. It might be suggested to initiate deferasirox as early as possible due to its efficacy profile and convenient administration regimen. A higher adverse event rate, however,may necessitate for careful monitoring of the patient's clinical status while using deferasirox.
Abstract
Deferoxamine has for decades been the standard for iron chelation therapy, but requires administration as a slow continuous subcutaneous or intravenous infusions five to seven times per week, potentially leading to poor compliance, reduced effectiveness. Deferasirox was developed in response to the need for an oral iron chelating agent. Its convenient, once-daily,oral administration schedule offers the potential to improve compliance. However, long-term efficacy and safety remain to be established. This study evaluated the efficacy and safety of deferasirox in pediatric patients who were switched off deferoxamine iron chelating therapy and introduced to deferasirox. It was conducted by method of retrospective chart review. Patients were divided into two groups. Group A(n=22)was constituted of patients who were converted from deferoxamine to deferasirox for their iron chelating therapy. Group B(n=24) was constituted of patients starting iron chelating therapy directly on deferasirox and had never changed. We evaluated the efficacy and the safety of deferasirox through intra-group and inter-group comparisons. The patients in group A, those who were administered deferoxamine, showed a trend of decrease in ferritin levels one month after administration(-222±117.16 ng/ml, p=0.845). In contrast, when the same patients changed their chelating agent to deferasirox, there was a tendency for ferritin levels to increase(+40.67±965.5 ng/ml, p=0.384). However, the ferritin level drop was not statistically different between the drugs (p=0.422). The use of deferasirox in group B decreased ferritin levels more than any other group, but was not statistically significant(-701.5±1687.5 ng/ml, p=0.053). Adverse events were more frequently observed with deferasirox than with deferoxamine in group A(59.1% vs 27.3%). The most common adverse events with deferasirox were gastrointestinal problems and LFT abnormality. On the other hand, skin problems were the most frequent adverse reactions to deferoxamine. Deferasirox showed similar efficacy to deferoxamine in terms of decreasing ferritin levels in pediatric patients. It might be suggested to initiate deferasirox as early as possible due to its efficacy profile and convenient administration regimen. A higher adverse event rate, however,may necessitate for careful monitoring of the patient's clinical status while using deferasirox.
참고문헌 (26)
- Porter J.B, "Practical management of ironoverload", Br J Haematol, 115, pp.239~252 (2001)
- Britton R.S, "Iron toxicityand chelation therapy", Int J Hematol, 76, pp.219~228 (2002)
- Paivi Halonen, "Iron overloadin children who are treated for acutelymphoblastic leukemia estimated by liversiderosis and serum iron parameters", Pediatrics, 111(1), pp.91~96 (2003)
- Chotsampancharon T, "Iron overloadin survivors of childhood leukemiaafter allogeneic hematopoietic stem celltransplantation", pp.1~5 (2008), Pediatr Transplant
- Davis B.A, "Result of long termiron chelation treatment with deferoxamine", Adv Exp Med Biol, 509, pp.91~125 (2002)
- Gabutti V, "Results of long-termiron-chelating therapy", Acta Haematol, 95, pp.26~36 (1996)
- Cabantchik Z.I, "LPI-labileplasma iron in iron overload", Best PractRes Clin Haematol, 18, pp.277~287 (2005)
- . NorvatisPharmaceuticals Corporation, , 2002
- Thomas E. Dela, "Consequencesand costs of noncompliance with iron chelationtherapy in patients with transfusion-dependentthalassemia: a literature review", Transfusion, 47, pp.1919~1929 (2007)
- Brittenham G.M, "Efficacyof deferoxamine in preventing complicationsof iron overload in patients withthalassemia major", N Eng J Med, 331, pp.567~573 (1994)
- Cohen A.R, "New Advances in IronChelation Therapy", Hematology Am SocHematol Educ Program, 42~47 (2006)
- Stumpf J.L, "Deferasirox", Am J HealthSyst Pharm, 64(6), pp.606~616 (2007)
- Elliott Vichinsky, "A randomised comparison of deferasiroxversus deferoxamine for the treatmentof transfusional iron overload in sicklecell disease", British Journal of Haematology, 136, pp.501~508 (2006)
- Porter J, "Relative responseof patients with mtelodysplastic syndromesand other transfusion-dependentanemias to deferasirox (ICL670): a1-yr prospective study", Eur J Haematol, 80(2), pp.168~176 (2008)
- Galanello R, "Phase II clinicalevaluation of deferasirox, a once-dailyoral chelating agent, in pediatricpatients with β-thalassemia major", Haematologica, 91, pp.1343~1351 (2006)
- Olivieri N.F, "Ironchelatingtherapy and treatment of thalassemia", Blood, 89, pp.739~761 (1997)
- Olivieri N.F, "Survival in medically treated patientswith homozygous beta-thalassemia", NEng J Med, 331, pp.574~578 (1994)
- Vermylen C, "What is new in iron overload", Eur J Pediatr, 167, pp.377~381 (2008)
- Malcovati L, "Prognosticfactors and life expectancy in myelodysplasticsyndromes classified according toWHO criteria: a basis for clinical decisionmaking", J Clin Oncol, 23, pp.7594~7603 (2005)
- Arboretti R, "Pharmacosurveillanceand quality of care of thalassemicpatients", Eur J Clin Pharmacol, 56, pp.915~922 (2001)
- Gabutti V, "Results of longtermiron-chelating therapy", Acta Haematol, 95, pp.26~36 (1996)
- Cappellini M.D., "ProspectiveEvaluation of Patient-ReportedOutcomes During Treatment withDeferasirox of Deferoxamine for IronOverload in Patients with β -Thalassemia", Clinical Therapeutics, 29, pp.5~ (2007)
- Rahav G, "Severe infections inthalassaemic patients: prevalence andpredisposing factors", Br J Haematol, 133(6), pp.667~674 (2006)
- Inflammation and oxidant stress in β-thalassemia patients treated with ironchelators deferasirox or deferoxamine, "an ancillary study of the NorvatisCICL670A0107 trial", Haematologica, 93(6), pp.817~825 (2008)
- Cappellini M.D., "Aphase 3 study of deferasirox (ICL670), aonce-daily oral chelator, in patientswith β-thalassemia", Blood, 107, pp.3455~3462 (2006)
- Piga A, "Randomized phaseII trial of deferasirox (Exjade, ICL670),a once-daily, orally-administered ironchelator, in comparison to deferoxaminein thalassemia patients with transfusionaliron overload", Haematologica, 91, pp.873~880 (2006)