title: Terminal Complement Inhibitor Eculizumab in Adult Patients With Atypical Hemolytic Uremic Syndrome: A Single-Arm, Open-Label Trial.
abstract: BACKGROUND
  Atypical hemolytic uremic syndrome (aHUS) is a rare genetic life-threatening disease of chronic uncontrolled complement activation leading to thrombotic microangiopathy (TMA) and severe end-organ damage. Eculizumab, a terminal complement inhibitor approved for aHUS treatment, was reported to improve hematologic and renal parameters in 2 prior prospective phase 2 studies. This is the largest prospective study of eculizumab in aHUS to date, conducted in an adult population.
  
  
  METHODS
  Open-label single-arm phase 2 trial.
  
  
  METHODS
  Patients 18 years or older with aHUS (platelet count <150 × 10(3)/μL, hemoglobin ≤ lower limit of normal, lactate dehydrogenase ≥1.5 × upper limit of normal [ULN], and serum creatinine ≥ ULN) were included in this multicenter multinational study.
  
  
  METHODS
  Intravenous eculizumab (900mg/wk for 4 weeks, 1,200mg at week 5 and then every 2 weeks) for 26 weeks.
  
  
  METHODS
  Primary end point was complete TMA response within 26 weeks, defined as hematologic normalization (platelet count ≥150 × 10(3)/μL, LDH ≤ ULN), and preservation of kidney function (<25% serum creatinine increase from baseline), confirmed by 2 or more consecutive measurements obtained 4 or more weeks apart.
  
  
  RESULTS
  41 patients were treated; 38 (93%) completed 26 weeks of treatment. 30 (73%) were included during their first TMA manifestation. 30 (73%) had complete TMA response. Platelet counts and estimated glomerular filtration rates increased from baseline (P<0.001). All 35 patients on baseline plasma exchange/plasma infusion discontinued by week 26. Of 24 patients requiring baseline dialysis, 5 recovered kidney function before eculizumab initiation and 15 of the remaining 19 (79%) discontinued dialysis during eculizumab treatment. No patients lost existing transplants. Quality-of-life measures were significantly improved. Two patients developed meningococcal infections; both recovered, and 1 remained on eculizumab treatment.
  
  
  CONCLUSIONS
  Single-arm open-label design.
  
  
  CONCLUSIONS
  Results highlight the benefits of eculizumab in adult patients with aHUS: improvement in hematologic, renal, and quality-of-life parameters; dialysis discontinuation; and transplant protection.
authors.affiliation: Department of Nephrology and Immunology, UMR 643, CHU de Nantes, Nantes, France. Electronic address: fadi.fakhouri@univ-nantes.fr.
authors.forename: Fadi
authors.initials: F
authors.lastname: Fakhouri
authors.affiliation: Department of Nephrology and Immunology, UMR 643, CHU de Nantes, Nantes, France.
authors.forename: Maryvonne
authors.initials: M
authors.lastname: Hourmant
authors.affiliation: Nephrology and Urology Department, Hospital Clinic, University of Barcelona, Barcelona, Spain.
authors.forename: Josep M
authors.initials: JM
authors.lastname: Campistol
authors.affiliation: Division of Hematology, The Ohio State University Medical Center, Columbus, OH.
authors.forename: Spero R
authors.initials: SR
authors.lastname: Cataland
authors.affiliation: Nefrología, Hospital Universitario Reina Sofía, Córdoba, Spain.
authors.forename: Mario
authors.initials: M
authors.lastname: Espinosa
authors.affiliation: Houston Methodist Research Institute, Houston, TX.
authors.forename: A Osama
authors.initials: AO
authors.lastname: Gaber
authors.affiliation: Clinic for Nephrology and Hypertension, Hannover Medical School, Hannover, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Menne
authors.affiliation: Division of Nephrology, Careggi University Hospital, Florence, Italy.
authors.forename: Enrico E
authors.initials: EE
authors.lastname: Minetti
authors.affiliation: Department of Nephrology, CHU Lille, Lille, France.
authors.forename: François
authors.initials: F
authors.lastname: Provôt
authors.affiliation: Urgences Néphrologiques et Transplantation Rénale, Hôpital Tenon and Université Paris VI, Paris, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Rondeau
authors.affiliation: IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Centro Anna Maria Astori, Bergamo, Italy.
authors.forename: Piero
authors.initials: P
authors.lastname: Ruggenenti
authors.affiliation: Service of Nephrology, Dialysis and Transplantation, Centre Hospitalier Universitaire, Liège, Belgium.
authors.forename: Laurent E
authors.initials: LE
authors.lastname: Weekers
authors.affiliation: Alexion Pharmaceuticals, Inc, Cheshire, CT.
authors.forename: Masayo
authors.initials: M
authors.lastname: Ogawa
authors.affiliation: Alexion Pharmaceuticals, Inc, Cheshire, CT.
authors.forename: Camille L
authors.initials: CL
authors.lastname: Bedrosian
authors.affiliation: Adult Kidney Transplant Unit, Université Paris Descartes and Hôpital Necker, Paris, France.
authors.forename: Christophe M
authors.initials: CM
authors.lastname: Legendre
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D065766:Atypical Hemolytic Uremic Syndrome / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012074:Remission Induction; D055815:Young Adult
chemical_list: D061067:Antibodies, Monoclonal, Humanized; C481642:eculizumab
keywords: Eculizumab; Soliris; TMA response; adults; atypical hemolytic uremic syndrome (aHUS); clinical trial; hematologic normalization; hemoglobin; kidney disease; lactate dehydrogenase (LDH); platelet count; renal function; terminal complement inhibitor; thrombotic microangiopathy (TMA)