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De novo weekly and biweekly darbepoetin alfa dosing in pediatric patients with chronic kidney disease

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Abstract

Background

Darbepoetin alfa is a commonly prescribed erythropoiesis-stimulating agent (ESA) for correcting anemia in pediatric chronic kidney disease (CKD) patients. However, little information exists on its use in ESA-naïve patients. This study evaluated the efficacy and safety of darbepoetin alfa in pediatric patients initiating ESA therapy.

Methods

One-hundred sixteen pediatric ESA-naïve subjects (aged 1–18 years) with CKD stages 3–5D and hemoglobin (Hb) <10 g/dl from 43 centers in the US, Europe, and Mexico were randomized by age (three groups) and dialysis status (yes vs. no) to receive darbepoetin alfa once weekly (QW) or every 2 weeks (Q2W) subcutaneously (not on dialysis and peritoneal dialysis subjects) and intravenously (hemodialysis subjects). The drug was titrated to achieve Hb levels of 10.0–12.0 g/dl over 25 weeks. Patient- and parent-reported health-related outcomes were measured by the Pediatric Quality of Life Inventory (PedsQL™) in children ≥2 years.

Results

In both groups, mean Hb concentrations increased to ≥11.0 g/dl over the first 3 months of treatment and remained stable within the 10.0–12.0 g/dl target range. The median time to achieve hemoglobin ≥10 g/dl was slightly longer for subjects <12 years (QW and Q2W, both 28 days) vs. those ≥12 years (23 and 22 days, respectively). Adverse event profiles were similar between groups, with QW, four (7%) and Q2W, five (9%). PedsQL™ scores showed modest increases.

Conclusions

Darbepoetin alfa can be safely administered either QW or Q2W to ESA-naïve pediatric patients with CKD-related anemia to achieve Hb targets of 10.0–12.0 g/dl.

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Acknowledgments

The authors wish to thank Holly Tomlin (employee and stockholder, Amgen Inc.) for medical writing assistance. The initial drafts of the Introduction and Discussion were written by the first and senior authors, and all authors contributed to the development of the manuscript, provided substantial edits to the drafts and approved the final version of the manuscript in accordance with ICMJE criteria for authorship. All authors agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

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Authors and Affiliations

  1. University of Missouri-Kansas City School of Medicine, Children’s Mercy Kansas City, Kansas City, MO, 64108, USA

    Bradley A. Warady

  2. Department of Pediatrics, University of Virginia School of Medicine, Charlottesville, VA, USA

    John Barcia

  3. Rady Children’s Hospital, University of California at San Diego, San Diego, CA, USA

    Nadine Benador

  4. Center for Pediatrics, Vilnius University, Vilnius, Lithuania

    Augustina Jankauskiene

  5. Amgen Inc., Thousand Oaks, CA, USA

    Kurt Olson & Jeffrey Petersen

  6. 1st Dept Pediatric Children’s Hospital, Comenius University, Bratislava, Slovakia

    Ludmila Podracka

  7. Children’s City Hospital #1, St. Petersburg, Russia

    Aleksey Shavkin

  8. Department of Pediatric Medicine – Renal, Texas Children’s Hospital, Houston, TX, USA

    Poyyapakkam Srivaths

  9. Division of Pediatric Nephrology, Stanford University, Palo Alto, CA, USA

    Cynthia J. Wong

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  1. Bradley A. Warady
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  9. Cynthia J. Wong
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  10. Jeffrey Petersen
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Corresponding author

Correspondence to Bradley A. Warady.

Ethics declarations

All procedures were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975 (revised 2005). A signed informed consent form by the patient’s parent or guardian was required for all patients before randomization by an interactive voice response system. A signed assent form was requested from patients ≥7 years old.

Conflict of interest

This study was funded by Amgen Inc. Authors K.O. and J.P. are employees and stockholders of Amgen Inc. B.A.W., J.B., N.B., A.J., L.P., A.S., P.S. and C.J.W. were investigators when the study was conducted.

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Warady, B.A., Barcia, J., Benador, N. et al. De novo weekly and biweekly darbepoetin alfa dosing in pediatric patients with chronic kidney disease. Pediatr Nephrol 33, 125–137 (2018). https://doi.org/10.1007/s00467-017-3758-5

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  • DOI: https://doi.org/10.1007/s00467-017-3758-5

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