Efficacy and Long-Term Safety of C.E.R.A. Maintenance in Pediatric Hemodialysis Patients with Anemia of CKD

Fischbach, Michel; Wühl, Elke; Reigner, Sylvie C. Meyer; Morgan, Zoe; Schaefer, Franz

doi:10.2215/cjn.03570417

Cited by 18 publications

(22 citation statements)

References 13 publications

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“…In a typical 9‐year‐old patient, with a body weight of 25 kg, representing the 6‐11 years age category, Hb 0 is expected to be 8.1 g dL −1 . This may explain why younger patients required higher doses relative to their starting dose compared to older patients to achieve the same target of Hb of 10–12 g dL −1 .…”

Section: Discussionmentioning

confidence: 99%

“…in the anaemia correction setting, one in patients on dialysis (PK data from 59 patients) and one in patients not on dialysis (PK data from 65 patients), and from the DOLPHIN study of IV C.E.R.A. in paediatric patients (PK data from 63 patients). Details of the studies and data used in this analysis are shown in Table .…”

Section: Methodsmentioning

confidence: 99%

“…Details of the studies and data used in this analysis are shown in Table . In the DOLPHIN study, two conversion factors were tested sequentially . In group 1 (intermediate conversion factor, first 16 patients), the starting dose was 4 μg every 4 weeks for each weekly dose of 250 IU epoetin alfa/beta or 1.1 μg darbepoetin alfa.…”

Section: Methodsmentioning

confidence: 99%

“…This analysis showed that the lower limit of the 95% confidence interval for average change in Hb concentration was below −1.0 g dL −1 and a second group with a conversion factor yielding higher drug exposure was tested. In this group (group 2, higher conversion factor), the starting dose was doubled to 4 μg every 4 weeks for each weekly dose of 125 IU epoetin alfa/beta or 0.55 μg darbepoetin alfa …”

Section: Methodsmentioning

confidence: 99%

“…In the DOLPHIN study (NH19707, NCT00717366) in a paediatric population, patients aged 5–17 years on haemodialysis with stable chronic anaemia being treated with epoetin alfa/beta or darbepoetin alfa were switched to IV C.E.R.A. for 20 weeks . This study established a dose conversion factor of four times the previous weekly dose (IU) of epoetin beta divided by 125, or four times the previous weekly dose of darbepoetin alfa (μg) divided by 0.55 to give the 4‐weekly starting dose (in μg) of C.E.R.A.…”

Section: Introductionmentioning

confidence: 99%

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Model‐based approach for methoxy polyethylene glycol‐epoetin beta drug development in paediatric patients with anaemia of chronic kidney disease

Chanu

Schaefer

Warady

et al. 2020

Brit J Clinical Pharma

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Aims Methoxy polyethylene glycol‐epoetin beta (continuous erythropoietin receptor activator, C.E.R.A.) is used for the treatment of anaemia in adults with chronic kidney disease (CKD). Patients treated with shorter‐acting erythropoiesis‐stimulating agents up to three times weekly can be switched to once‐monthly C.E.R.A.. Doses can be adjusted on a monthly basis based on haemoglobin (Hb) levels during the preceding period. A model‐based approach was applied to optimise C.E.R.A. development, more specifically the confirmatory trial of the paediatric plan. Methods Pharmacokinetic and pharmacodynamic data from a phase II paediatric study and phase II and III adult studies were analysed together using modelling and simulation to determine the pharmacokinetic/pharmacodynamic characteristics of C.E.R.A. in a broad population. Model‐based simulations of C.E.R.A. treatment outcomes in paediatric patients were performed, notably when administered subcutaneously and compared to clinical and real‐world data. Results Age and body weight explained differences in pharmacokinetics, while the pharmacodynamic characteristics of C.E.R.A. were similar between adult and paediatric populations. Simulated Hb levels (mean and 95% prediction interval 10.9 [10.6, 11.2] g dL−1) and C.E.R.A. doses (median and 95% prediction interval 105 [72, 159] μg) 20 weeks after switching to subcutaneous C.E.R.A. were confirmed by observed real‐world data from International Pediatric Dialysis Network registries (mean Hb was 10.8 g dL−1 and median C.E.R.A. dose was 100 μg). Conclusions These analyses have facilitated optimisation of the C.E.R.A. development programme in paediatric patients with anaemia of CKD to provide this patient population with faster access to the drug while avoiding unnecessary clinical trial exposure and related monitoring burden in children.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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