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Eculizumab is a safe and effective treatment in pediatric patients with atypical hemolytic uremic syndrome

(2016) KIDNEY INTERNATIONAL. 89(3). p.701-711
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Abstract
Atypical hemolytic uremic syndrome (aHUS) is caused by alternative complement pathway dysregulation, leading to systemic thrombotic microangiopathy (TMA) and severe end-organ damage. Based on 2 prospective studies in mostly adults and retrospective data in children, eculizumab, a terminal complement inhibitor, is approved for aHUS treatment. Here we prospectively evaluated efficacy and safety of weight-based dosing of eculizumab in eligible pediatric patients with aHUS in an open-label phase II study. The primary end point was complete TMA response by 26 weeks. Twenty-two patients (aged 5 months-17 years) were treated; 16 were newly diagnosed, 12 had no prior plasma exchange/infusion during current TMA symptomatology, 11 received baseline dialysis, and 2 had prior renal transplants. By week 26, 14 achieved a complete TMA response, 18 achieved hematologic normalization, and 16 had 25% or better improvement in serum creatinine. Plasma exchange/infusion was discontinued in all, and 9 of the 11 patients who required dialysis at baseline discontinued, whereas none initiated new dialysis. Eculizumab was well tolerated; no deaths or meningococcal infections occurred. Bone marrow failure, wrist fracture, and acute respiratory failure were reported as unrelated severe adverse events. Thus, our findings establish the efficacy and safety of eculizumab for pediatric patients with aHUS and are consistent with proposed immediate eculizumab initiation following diagnosis in children.
Keywords
children, aHUS, eculizumab, kidney disease, pediatric, thrombotic microangiopathy, COMPLEMENT INHIBITOR ECULIZUMAB, CLINICAL CHARACTERISTICS, RENAL-TRANSPLANT, MUTATIONS, THERAPY, CHILDREN, INSIGHTS, IMPACT, AHUS, EFFICACY

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Chicago
Greenbaum, Larry A, Marc Fila, Gianluigi Ardissino, Samhar I Al-Akash, Jonathan Evans, Paul Henning, Kenneth V Lieberman, et al. 2016. “Eculizumab Is a Safe and Effective Treatment in Pediatric Patients with Atypical Hemolytic Uremic Syndrome.” Kidney International 89 (3): 701–711.
APA
Greenbaum, L. A., Fila, M., Ardissino, G., Al-Akash, S. I., Evans, J., Henning, P., Lieberman, K. V., et al. (2016). Eculizumab is a safe and effective treatment in pediatric patients with atypical hemolytic uremic syndrome. KIDNEY INTERNATIONAL, 89(3), 701–711.
Vancouver
1.
Greenbaum LA, Fila M, Ardissino G, Al-Akash SI, Evans J, Henning P, et al. Eculizumab is a safe and effective treatment in pediatric patients with atypical hemolytic uremic syndrome. KIDNEY INTERNATIONAL. 2016;89(3):701–11.
MLA
Greenbaum, Larry A, Marc Fila, Gianluigi Ardissino, et al. “Eculizumab Is a Safe and Effective Treatment in Pediatric Patients with Atypical Hemolytic Uremic Syndrome.” KIDNEY INTERNATIONAL 89.3 (2016): 701–711. Print.
@article{7086892,
  abstract     = {Atypical hemolytic uremic syndrome (aHUS) is caused by alternative complement pathway dysregulation, leading to systemic thrombotic microangiopathy (TMA) and severe end-organ damage. Based on 2 prospective studies in mostly adults and retrospective data in children, eculizumab, a terminal complement inhibitor, is approved for aHUS treatment. Here we prospectively evaluated efficacy and safety of weight-based dosing of eculizumab in eligible pediatric patients with aHUS in an open-label phase II study. The primary end point was complete TMA response by 26 weeks. Twenty-two patients (aged 5 months-17 years) were treated; 16 were newly diagnosed, 12 had no prior plasma exchange/infusion during current TMA symptomatology, 11 received baseline dialysis, and 2 had prior renal transplants. By week 26, 14 achieved a complete TMA response, 18 achieved hematologic normalization, and 16 had 25\% or better improvement in serum creatinine. Plasma exchange/infusion was discontinued in all, and 9 of the 11 patients who required dialysis at baseline discontinued, whereas none initiated new dialysis. Eculizumab was well tolerated; no deaths or meningococcal infections occurred. Bone marrow failure, wrist fracture, and acute respiratory failure were reported as unrelated severe adverse events. Thus, our findings establish the efficacy and safety of eculizumab for pediatric patients with aHUS and are consistent with proposed immediate eculizumab initiation following diagnosis in children.},
  author       = {Greenbaum, Larry A and Fila, Marc and Ardissino, Gianluigi and Al-Akash, Samhar I and Evans, Jonathan and Henning, Paul and Lieberman, Kenneth V and Maringhini, Silvio and Pape, Lars and Rees, Lesley and van de Kar, Nicole CAJ and Vande Walle, Johan and Ogawa, Masayo and Bedrosian, Camille L and Licht, Christoph},
  issn         = {0085-2538},
  journal      = {KIDNEY INTERNATIONAL},
  keyword      = {children,aHUS,eculizumab,kidney disease,pediatric,thrombotic microangiopathy,COMPLEMENT INHIBITOR ECULIZUMAB,CLINICAL CHARACTERISTICS,RENAL-TRANSPLANT,MUTATIONS,THERAPY,CHILDREN,INSIGHTS,IMPACT,AHUS,EFFICACY},
  language     = {eng},
  number       = {3},
  pages        = {701--711},
  title        = {Eculizumab is a safe and effective treatment in pediatric patients with atypical hemolytic uremic syndrome},
  url          = {http://dx.doi.org/10.1016/j.kint.2015.11.026},
  volume       = {89},
  year         = {2016},
}

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