title: Eculizumab is a safe and effective treatment in pediatric patients with atypical hemolytic uremic syndrome.
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.
authors.affiliation: Emory University and Children's Healthcare of Atlanta, Atlanta, Georgia, USA. Electronic address: lgreen6@emory.edu.
authors.forename: Larry A
authors.initials: LA
authors.lastname: Greenbaum
authors.affiliation: CHRU de Montpellier - Hôpital Arnaud de Villeneuve, Montpellier, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Fila
authors.affiliation: Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
authors.forename: Gianluigi
authors.initials: G
authors.lastname: Ardissino
authors.affiliation: Driscoll Children's Hospital, Corpus Christi, Texas, USA.
authors.forename: Samhar I
authors.initials: SI
authors.lastname: Al-Akash
authors.affiliation: Nottingham University Hospitals, Nottingham, United Kingdom.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Evans
authors.affiliation: Women's and Children's Hospital, North Adelaide, South Australia, Australia.
authors.forename: Paul
authors.initials: P
authors.lastname: Henning
authors.affiliation: Hackensack University Medical Center, Hackensack, New Jersey, USA.
authors.forename: Kenneth V
authors.initials: KV
authors.lastname: Lieberman
authors.affiliation: G. Di Cristina Children's Hospital, Palermo, Italy.
authors.forename: Silvio
authors.initials: S
authors.lastname: Maringhini
authors.affiliation: Hannover Medical School, Hannover, Germany.
authors.forename: Lars
authors.initials: L
authors.lastname: Pape
authors.affiliation: Great Ormond Street Hospital for Children NHS Foundation Trust, London, United Kingdom.
authors.forename: Lesley
authors.initials: L
authors.lastname: Rees
authors.affiliation: Radboud University Medical Centre, Nijmegen, The Netherlands.
authors.forename: Nicole C A J
authors.initials: NC
authors.lastname: van de Kar
authors.affiliation: University Hospital Ghent, Ghent, Belgium.
authors.forename: Johan
authors.initials: J
authors.lastname: Vande Walle
authors.affiliation: Alexion Pharmaceuticals, Inc., Cheshire, Connecticut, USA.
authors.forename: Masayo
authors.initials: M
authors.lastname: Ogawa
authors.affiliation: Alexion Pharmaceuticals, Inc., Cheshire, Connecticut, USA.
authors.forename: Camille L
authors.initials: CL
authors.lastname: Bedrosian
authors.affiliation: The Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: Christoph
authors.initials: C
authors.lastname: Licht
mesh_terms: D000293:Adolescent; D000367:Age Factors; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D065766:Atypical Hemolytic Uremic Syndrome / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology; D001315:Australia; D002648:Child; D002675:Child, Preschool; D003167:Complement Activation / Q000187:drug effects*; D051056:Complement Inactivating Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D005060:Europe; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D009656:North America; D010951:Plasma Exchange; D011446:Prospective Studies; D006435:Renal Dialysis; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D051056:Complement Inactivating Agents; C481642:eculizumab
keywords: aHUS; children; eculizumab; kidney disease; pediatric; thrombotic microangiopathy