Terminal Complement Inhibitor Eculizumab in Adult Patients with Atypical Hemolytic Uremic Syndrome: A Single-Arm, Open-Label Trial

Fadi Fakhouri, Maryvonne Hourmant, Josep M. Campistol, Spero R. Cataland, Mario Espinosa, A. Osama Gaber, Jan Menne, Enrico E. Minetti, François Provôt, Eric Rondeau, Piero Ruggenenti, Laurent E. Weekers, Masayo Ogawa, Camille L. Bedrosian, Christophe M. Legendre

Research output: Contribution to journalArticlepeer-review

227 Scopus citations


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. Study Design: Open-label single-arm phase 2 trial. Setting & Participants: Patients 18 years or older with aHUS (platelet count <150 × 103/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. Intervention Intravenous eculizumab (900 mg/wk for 4 weeks, 1,200 mg at week 5 and then every 2 weeks) for 26 weeks. Outcomes: & Measurements Primary end point was complete TMA response within 26 weeks, defined as hematologic normalization (platelet count ≥150 × 103/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. Limitations: 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.

Original languageEnglish (US)
Pages (from-to)84-93
Number of pages10
JournalAmerican Journal of Kidney Diseases
Issue number1
StatePublished - Jul 1 2016


  • 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)

ASJC Scopus subject areas

  • Nephrology


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