Contributions
Abstract: PB1812
Type: Publication Only
Session title: Thalassemias
Background
Deferasirox (DFX) is once-daily oral iron chelator that was developed out of need for a long-acting chelator for patients with chronic iron overload. The first marketed formulation was a dispersible tablet (DT) thathad to be mixed inalarge amount of liquid and to be taken on an empty stomach. In addition to being unpalatable, it was commonly related to gastrointestinal symptoms. In that context, a new formulationin in the form of film coated tablet (FCT) was developed. FCT is still given once-daily, but can be taken with a light meal and differs with regards to excipients, offering improved palatability and tolerance.
Aims
To retrospectively report on the long-term experience of DFX use in transfusion-dependent thalassemia (TDT) children followed at a single Unit and to present a comparison between its two formulations.
Methods
Medical records of patients who received DFX were retrospectively evaluated. Data regarding demographics, duration and dose of chelation, renal and liver function, ferritin levels, and clinical adverse events were recorded. Statistical analysis was performed using the Wilcoxon test.
Results
A total of 44 patients treated with DFX DT were identified, between 2003 and 2016. Mean age at time of DFX DT exposure was 7.6(2– 15.3) years. Μean duration of exposure was 58.3 (3-141) months and mean daily dose 23.4(10-40)mg/kg. Prior to initiation, mean ferritin levels were 1094.7 (114–2760) ng/ml and at end of study 1149.1 (216-3184) ng/ml(P=0.6). At study entry mean creatinine levels were 0.49 (0.34-0.84) mg/dl and at end of study 0.7 (0.37-1.06) mg/dl (P<0.0001).
During follow up 26/44 patients (59%) temporarily interrupted treatment, at one or more time points, on account of the following: 7/26 patients(26.9%) due to increased liver enzyme levels, 4/26(15,4%) due to renal dysfunction including increased creatinine levels and/or increased protein or calcium output, 4/26(15.4%) due to abnormal liver enzyme levels and concurrent renal dysfunction,, 2/26(7.7%) due to epigastralgia, and 1/26 (3.8%) due to either rash, epigastralgia or pregnancy. In 17/44 patients (38.6%) a switch to another chelator was decided due to recurrent adverse events after drug re-initiation.
A total of 27 children received DFX FCT after it was marketed in September 2017 until February 2021. Mean age at initiation was 12.9 (2 –18) years. Mean exposure time was 27.15 (8-40) months and mean daily dose was 16.4 (10-27.5) mg/kg. Prior to DFX FCT mean ferritin levels were 1197.2 (438–2094) ng/ml and mean creatinine levels 0.66 (0.4-0.98) mg/dl. At end of study mean ferritin and creatinine levels were 1300 (515-2829) ng/ml (P=0.75) and 0.7 (0.38-0.96) mg/dl (P=0.15), respectively.
During follow up 5/27 patients (18.5%) temporarily interrupted treatment due to increased liver enzyme levels (4/5,80%) or increased creatinine levels (1/5,20%). In total, 6/27 patients (22.2%) switched to other chelationregimens.
Conclusion
DFX demonstrated an adequately efficacious and safe profile in a pediatric thalassemia cohort over almost 2 decades. Although experience with DFX FCT is comparably limited, results are encouraging, especially in terms of number of related renal adverse events. The new formulation’s favorable safety profile along with its improved palatability may offer, in the long run, better adherence and optimal control of iron overload‐related complications.
Keyword(s): Chelation, Deferasirox, Thalassemia
Abstract: PB1812
Type: Publication Only
Session title: Thalassemias
Background
Deferasirox (DFX) is once-daily oral iron chelator that was developed out of need for a long-acting chelator for patients with chronic iron overload. The first marketed formulation was a dispersible tablet (DT) thathad to be mixed inalarge amount of liquid and to be taken on an empty stomach. In addition to being unpalatable, it was commonly related to gastrointestinal symptoms. In that context, a new formulationin in the form of film coated tablet (FCT) was developed. FCT is still given once-daily, but can be taken with a light meal and differs with regards to excipients, offering improved palatability and tolerance.
Aims
To retrospectively report on the long-term experience of DFX use in transfusion-dependent thalassemia (TDT) children followed at a single Unit and to present a comparison between its two formulations.
Methods
Medical records of patients who received DFX were retrospectively evaluated. Data regarding demographics, duration and dose of chelation, renal and liver function, ferritin levels, and clinical adverse events were recorded. Statistical analysis was performed using the Wilcoxon test.
Results
A total of 44 patients treated with DFX DT were identified, between 2003 and 2016. Mean age at time of DFX DT exposure was 7.6(2– 15.3) years. Μean duration of exposure was 58.3 (3-141) months and mean daily dose 23.4(10-40)mg/kg. Prior to initiation, mean ferritin levels were 1094.7 (114–2760) ng/ml and at end of study 1149.1 (216-3184) ng/ml(P=0.6). At study entry mean creatinine levels were 0.49 (0.34-0.84) mg/dl and at end of study 0.7 (0.37-1.06) mg/dl (P<0.0001).
During follow up 26/44 patients (59%) temporarily interrupted treatment, at one or more time points, on account of the following: 7/26 patients(26.9%) due to increased liver enzyme levels, 4/26(15,4%) due to renal dysfunction including increased creatinine levels and/or increased protein or calcium output, 4/26(15.4%) due to abnormal liver enzyme levels and concurrent renal dysfunction,, 2/26(7.7%) due to epigastralgia, and 1/26 (3.8%) due to either rash, epigastralgia or pregnancy. In 17/44 patients (38.6%) a switch to another chelator was decided due to recurrent adverse events after drug re-initiation.
A total of 27 children received DFX FCT after it was marketed in September 2017 until February 2021. Mean age at initiation was 12.9 (2 –18) years. Mean exposure time was 27.15 (8-40) months and mean daily dose was 16.4 (10-27.5) mg/kg. Prior to DFX FCT mean ferritin levels were 1197.2 (438–2094) ng/ml and mean creatinine levels 0.66 (0.4-0.98) mg/dl. At end of study mean ferritin and creatinine levels were 1300 (515-2829) ng/ml (P=0.75) and 0.7 (0.38-0.96) mg/dl (P=0.15), respectively.
During follow up 5/27 patients (18.5%) temporarily interrupted treatment due to increased liver enzyme levels (4/5,80%) or increased creatinine levels (1/5,20%). In total, 6/27 patients (22.2%) switched to other chelationregimens.
Conclusion
DFX demonstrated an adequately efficacious and safe profile in a pediatric thalassemia cohort over almost 2 decades. Although experience with DFX FCT is comparably limited, results are encouraging, especially in terms of number of related renal adverse events. The new formulation’s favorable safety profile along with its improved palatability may offer, in the long run, better adherence and optimal control of iron overload‐related complications.
Keyword(s): Chelation, Deferasirox, Thalassemia