Beta talasemi major olgularında yeni oral demir şelatörü ICL670 ile desferrioksamin etkinliğinin karşılaştırıldığı 1 yıl süreli prospektif randomize faz III çalışma
Küçük Resim Yok
Tarih
2005
Yazarlar
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Ege Üniversitesi
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
ÖZET ?- talasemi major (TM) olgularında transfüzyonlarla kazanılan demir, yeterli şelasyon tedavisi ile etkin bir şekilde uzaklaştırılmazsa, ciddi morbidite ve erken ölüm nedenidir. Bu çalışma, TM olgularında, yeni deneysel oral demir şelatörü lCL670'in karaciğer demir yoğunluğu ve serum ferritin düzeylerini azaltmadaki etkinliği konvansiyonel demir şelatörü DFO ile 1 yıl süreli, prospektif, açık, randomize çalışma ile karşılaştırıldı. Oral demir şelatörü Deferipron (DF) kullanan olgu grubu randomizasyon dışı olarak çalışmaya katıldı. TM tanısıyla izlenen 38 hasta çalışmaya alındı. 14 hasta ICL670 kullanırken 12'er hastaya DFO ve DF uygulandı. Olgular 3,5 - 28 (16.6 ± 6.3) yaş aralığında olup 17 kız ve 21 erkekti. Çalışma öncesi tüm hastalar DFO şelasyonu almaktaydı. DFO 40-50 mg/kg/g haftanın 5 günü uygulandı. DF (LIPOMED, İsviçre) 75 mg/kg/g 3 dozda her gün verildi. ICL670 (Novartis, isviçre) ise karaciğer demir yoğunluğu temelinde 10, 20 veya 30 mg/kg/g tek dozda uygulandı, istatistiksel değerlendirme "SPSS 11.0 for Windows" kullanılarak yapıldı. Çalışma ilaçları genelde iyi tolere edildi. ICL670 ile ilişkili daha uzun süreli klinik çalışma sonuçlarına gereksinim olmakla beraber, her 3 tedavi modeli de güvenilir bulundu. ICL670 grubundan 1 olgu şiddetli transaminitis nedeniyle çalışma dışı kaldı. Karaciğer demir yoğunluğundaki değişime göre, ICL670 ve DF kullanan hastaların sırasıyla %31 ve %41'inde şelasyon başarılı bulundu. Buna karşın DFO kullanan olguların %92'de şelasyon başarılıydı. ICL670'i 30 mg/kg/g kullanan olguların %60'ının karaciğer demir yoğunluğu düşüş gösterdi. Tüm tedavi gruplarında, çalışma sonunda ortalama serum ferritin düzeyleri %20-40 arasında değişen düşüş gösterdi. ICL670'i 10 mg/kg/g dozda kullanan grubun serum ferritin ortalamasının çalışmanın başlangıcı ve sonu arasında değişim göstermediği görüldü. İCL670!in 20 ve 30 mg/kg/g dozlarda uygulandığı olgularda serum ferritin düzeylerinde %46 oranında azalma saptandı. Klinik etkinlik bakımından DFO, İCL670 ve DF'ye üstün bulundu. SCL670 ve DF'nin daha yüksek dozlarda veya kombine sağaltım modelleriyle etkinliklerinin artabileceği düşünüldü. Anahtar kelimeler: talasemi major, demir yükü, desferrioksamin, deferipron, ICL670 63
ABSTRACT Transfusional iron overload in the patients with S~thalassaemia major may lead to serious organ toxicity and early death if no iron excretion is achieved by a chelating agent. The efficacy of ICL670 at reducing liver iron concentration (LIC) and serum ferritin has been compared with desferrioxamine (DFO) in a randomised prospective 1-year study. Patients treated with single agent treatment of DFe (DF) were included in the comparison, partly without randomisation. A total of 38 patients with thalassaemia major were included, i.e. 12 patients into one of the following 3 arms; DF (LIPOMED AG, Switzerland) was given at a daily dose of 75 mg/kg as single agent and patients registered in the DFO arm received 40-50 mg/kg s.c. DFO 5 days a week. ICL670 (NOVARTİS, Switzerland) was given at a daily doses of 10, 20 or 30 mg/kg adjusted according to basal LIC values. All patients had been treated with DFO prior to the study. SPSS11.0 for Windows was used in statistical analysis. Although long-term studies are needed related with the safety of ICL670, all chelators were generally well tolerated during the study period. Only a patient treated in ICL670 arm dropped out from the study with severe transaminitis. LIC fell significantly by 41% in the DF, by 31% in the ICL670 and by 92% in the DFO arm after one year of study treatment. The decrease in LIC was achieved in 60% of patients who use ICL670 at the dose of 30 mg/kg/d. The mean ferritin values fell between 20-40% at the end of study in ail treatment arms. The decrease in serum ferritin was found 46% in the patients who received ICL670 at the doses of 20 and 30 mg/kg/d whereas it hasn't changed at the end of study in the patients receiving the chelator at the dose of 10 mg/kg/d. This study shows that the DFO were superior in reducing liver iron if compared to the DF and 1CL670 singie agent arms. DF and ICL670 would be more effective in increased doses of chelators or in individual combination regimens of the chelators. Key words: thalassaemia major, iron overload, desferrioxamine, deferiprone, 1CL670 64
ABSTRACT Transfusional iron overload in the patients with S~thalassaemia major may lead to serious organ toxicity and early death if no iron excretion is achieved by a chelating agent. The efficacy of ICL670 at reducing liver iron concentration (LIC) and serum ferritin has been compared with desferrioxamine (DFO) in a randomised prospective 1-year study. Patients treated with single agent treatment of DFe (DF) were included in the comparison, partly without randomisation. A total of 38 patients with thalassaemia major were included, i.e. 12 patients into one of the following 3 arms; DF (LIPOMED AG, Switzerland) was given at a daily dose of 75 mg/kg as single agent and patients registered in the DFO arm received 40-50 mg/kg s.c. DFO 5 days a week. ICL670 (NOVARTİS, Switzerland) was given at a daily doses of 10, 20 or 30 mg/kg adjusted according to basal LIC values. All patients had been treated with DFO prior to the study. SPSS11.0 for Windows was used in statistical analysis. Although long-term studies are needed related with the safety of ICL670, all chelators were generally well tolerated during the study period. Only a patient treated in ICL670 arm dropped out from the study with severe transaminitis. LIC fell significantly by 41% in the DF, by 31% in the ICL670 and by 92% in the DFO arm after one year of study treatment. The decrease in LIC was achieved in 60% of patients who use ICL670 at the dose of 30 mg/kg/d. The mean ferritin values fell between 20-40% at the end of study in ail treatment arms. The decrease in serum ferritin was found 46% in the patients who received ICL670 at the doses of 20 and 30 mg/kg/d whereas it hasn't changed at the end of study in the patients receiving the chelator at the dose of 10 mg/kg/d. This study shows that the DFO were superior in reducing liver iron if compared to the DF and 1CL670 singie agent arms. DF and ICL670 would be more effective in increased doses of chelators or in individual combination regimens of the chelators. Key words: thalassaemia major, iron overload, desferrioxamine, deferiprone, 1CL670 64
Açıklama
Anahtar Kelimeler
Çocuk Sağlığı ve Hastalıkları, Child Health and Diseases
