Observational study comparing long-term safety and efficacy of Deferasirox with Desferrioxamine therapy in chelation-naïve children with transfusional iron overload

AbstractDeferasirox (DFX) is the newest among three different chelators available to treat iron overload in iron-loading anaemias, firstly released as Dispersible Tablets (DT) and more recently replaced by Film-Coated Tablets (FCT). In this retrospective observational study, pharmacokinetics, pharmacodynamics, and safety features of DFX treatment were analyzed in 74 patients that took both formulations subsequently under clinical practice conditions. Bioavailability of DFX FCT compared to DT resulted higher than expected [Cmax: 99.5 (FCT) and 69.7 (DT) μMol/L; AUC: 1278 (FCT) and 846 (DT), P < 0.0001]. DFX FCT was also superior in scalability among doses. After one year of treatment for each formulation, no differences were observed between the treatments in the overall iron overload levels; however, DFX FCT but not DT showed a significant dose–response correlation [Spearman r (dose-serum ferritin variation): − 0.54, P < 0.0001]. Despite being administered at different dosages, the long-term safety profile was not different between formulations: a significant increase in renal impairment risk was observed for both treatments and it was reversible under strict monitoring (P < 0.002). Altogether, these data constitute a comprehensive comparison of DFX formulations in thalassaemia and other iron-loading anaemias, confirming the effectiveness and safety characteristics of DFX and its applicability for treatment tailoring.

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Long-term safety and efficacy of deferasirox in young pediatric patients with transfusional hemosiderosis: Results from a 5year observational study (ENTRUST)

Pediatric Blood & Cancer ◽

10.1002/pbc.26507 ◽

2017 ◽

Vol 64 (9) ◽

pp. e26507 ◽

Cited By ~ 7

Author(s):

Elliott Vichinsky ◽

Amal El-Beshlawy ◽

Azzam Al Zoebie ◽

Annie Kamdem ◽

Suzanne Koussa ◽

...

Keyword(s):

Observational Study ◽

Pediatric Patients ◽

Safety And Efficacy

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Long-term safety and efficacy of alogliptin, a DPP-4 inhibitor, in patients with type 2 diabetes: a 3-year prospective, controlled, observational study (J-BRAND Registry)

BMJ Open Diabetes Research & Care ◽

10.1136/bmjdrc-2020-001787 ◽

2021 ◽

Vol 9 (1) ◽

pp. e001787

Author(s):

Kohjiro Ueki ◽

Yukio Tanizawa ◽

Jiro Nakamura ◽

Yuichiro Yamada ◽

Nobuya Inagaki ◽

...

Keyword(s):

Type 2 Diabetes ◽

Observational Study ◽

Real World ◽

Safety And Efficacy ◽

The Real ◽

Real World Setting ◽

Group A ◽

Group B

IntroductionGiven an increasing use of dipeptidyl peptidase-4 (DPP-4) inhibitors to treat patients with type 2 diabetes mellitus in the real-world setting, we conducted a prospective observational study (Japan-based Clinical Research Network for Diabetes Registry: J-BRAND Registry) to elucidate the safety and efficacy profile of long-term usage of alogliptin.Research design and methodsWe registered 5969 patients from April 2012 through September 2014, who started receiving alogliptin (group A) or other classes of oral hypoglycemic agents (OHAs; group B), and were followed for 3 years at 239 sites nationwide. Safety was the primary outcome. Symptomatic hypoglycemia, pancreatitis, skin disorders of non-extrinsic origin, severe infections, and cancer were collected as major adverse events (AEs). Efficacy assessment was the secondary outcome and included changes in hemoglobin A1c (HbA1c), fasting blood glucose, fasting insulin and urinary albumin.ResultsOf the registered, 5150 (group A: 3395 and group B: 1755) and 5096 (3358 and 1738) were included for safety and efficacy analysis, respectively. Group A patients mostly (>90%) continued to use alogliptin. In group B, biguanides were the primary agents, while DPP-4 inhibitors were added in up to ~36% of patients. The overall incidence of AEs was similar between the two groups (42.7% vs 42.2%). Kaplan-Meier analysis revealed the incidence of cancer was significantly higher in group A than in group B (7.4% vs 4.8%, p=0.040), while no significant incidence difference was observed in the individual cancer. Multivariate Cox regression analysis revealed that the imbalanced patient distribution (more elderly patients in group A than in group B), but not alogliptin usage per se, contributed to cancer development. The incidence of other major AE categories was with no between-group difference. Between-group difference was not detected, either, in the incidence of microvascular and macrovascular complications. HbA1c and fasting glucose decreased significantly at the 0.5-year visit and nearly plateaued thereafter in both groups.ConclusionsAlogliptin as a representative of DPP-4 inhibitors was safe and durably efficacious when used alone or with other OHAs for patients with type 2 diabetes in the real world setting.

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Deferasirox (Exjade®), the Once-Daily Oral Iron Chelator, Demonstrates Safety and Efficacy in Patients with Sickle Cell Disease (SCD): 3.5-Year Follow-up.

Blood ◽

10.1182/blood.v112.11.1420.1420 ◽

2008 ◽

Vol 112 (11) ◽

pp. 1420-1420 ◽

Cited By ~ 7

Author(s):

Elliott Vichinsky ◽

Thomas Coates ◽

Alexis A Thompson ◽

Françoise Bernaudin ◽

Martha Rodriguez ◽

...

Keyword(s):

Renal Function ◽

Iron Overload ◽

Iron Concentration ◽

Transfusion Therapy ◽

Safety And Efficacy ◽

To Receive ◽

Dose Dependent ◽

Median Change

Abstract Background: Many patients with SCD require chronic transfusion therapy to manage the complications of their disease (eg stroke prevention); as a consequence, secondary iron overload may develop. Controlled data from patients with SCD receiving long-term iron chelation therapy, particularly renal function, are lacking. Cumulative 3.5-year safety and efficacy data are presented for adult and pediatric patients with SCD with transfusional iron overload treated with deferasirox (Exjade®) in a 4-year extension to a 1-year comparative study (109). Methods: Study 109 demonstrated similar dose-dependent liver iron concentration (LIC) reductions with deferasirox and deferoxamine (DFO) in SCD patients with iron overload. Eligible patients entered a 4-year extension phase and received deferasirox only; dose adjustments were based on monthly serum ferritin (SF) levels and safety assessments (adverse events [AEs] and laboratory parameters). Patients with abnormal renal function were excluded. Results: 132 patients (mean age ± SD of 19.1 ± 10.7 years) who were initially randomized in the core study to receive deferasirox are included in this analysis. The median duration of exposure to deferasirox was 37.4 months (3.1 years) at a mean dose of 18.4 ± 6.2 mg/kg/day. Mean iron intake over this period was 0.3 ± 0.1 mg/kg/day. 72 patients (54.5%) continue to receive deferasirox. Reasons for discontinuations include: AEs (n=11), consent withdrawal (n=24), lost to follow-up (n=9), unsatisfactory therapeutic effect (n=4), and other reasons (n=11). There was also one death reported post-liver transplantation, which was not considered by the investigator to be related to the study drug. The most frequent drug-related (investigator-assessed) AEs were nausea (n=20; 15.2%), diarrhea (n=14; 10.6%), vomiting (n=8; 6.1%) and abdominal pain (n=6; 4.5%). Nine patients (6.8%) had two consecutive increases in serum creatinine that were both >33% above baseline and above the upper limit of normal (ULN); however, there were no progressive increases. Five patients (3.8%) had an increase in alanine aminotransferase >10xULN on at least one visit; baseline levels were already >ULN in two patients. Mean daily dose of deferasirox increased from 15.4 ± 6.9 mg/kg/day at month 1 to 22.3 ± 7.3 mg/kg/day at month 42. Overall baseline median SF level was 3439 ng/mL (n=132), which decreased by 651 ng/mL (P=0.0533, Wilcoxon signed rank test; n=49) by month 42 (Figure 1). SF decreases were dose-dependent (data not shown). Figure 1. Mean dose and median change in SF during deferasirox treatment Figure 1. Mean dose and median change in SF during deferasirox treatment Conclusions: Patients with SCD and transfusional iron overload receiving long-term deferasirox demonstrated continued reduction in their body iron burden (according to SF levels), without an exposure-associated increase in AE incidence, or evidence of progressive renal dysfunction.

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