Terminal Complement Inhibitor Eculizumab in Atypical Hemolytic-Uremic Syndrome

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Background Atypical hemolytic-uremic syndrome is a genetic, life-threatening, chronic disease of complement-mediated thrombotic microangiopathy. Plasma exchange or infusion may transiently maintain normal levels of hematologic measures but does not treat the underlying systemic disease. Methods We conducted two prospective phase 2 trials in which patients with atypical hemolytic-uremic syndrome who were 12 years of age or older received eculizumab for 26 weeks and during long-term extension phases. Patients with low platelet counts and renal damage (in trial 1) and those with renal damage but no decrease in the platelet count of more than 25% for at least 8 weeks during plasma exchange or infusion (in trial 2) were recruited. The primary end points included a change in the platelet count (in trial 1) and thrombotic microangiopathy event-free status (no decrease in the platelet count of >25%, no plasma exchange or infusion, and no initiation of dialysis) (in trial 2). Results A total of 37 patients (17 in trial 1 and 20 in trial 2) received eculizumab for a median of 64 and 62 weeks, respectively. Eculizumab resulted in increases in the platelet count; in trial 1, the mean increase in the count from baseline to week 26 was 73x10(9) per liter (P<0.001). In trial 2, 80% of the patients had thrombotic microangiopathy event-free status. Eculizumab was associated with significant improvement in all secondary end points, with continuous, time-dependent increases in the estimated glomerular filtration rate (GFR). In trial 1, dialysis was discontinued in 4 of 5 patients. Earlier intervention with eculizumab was associated with significantly greater improvement in the estimated GFR. Eculizumab was also associated with improvement in health-related quality of life. No cumulative toxicity of therapy or serious infection-related adverse events, including meningococcal infections, were observed through the extension period. Conclusions Eculizumab inhibited complement-mediated thrombotic microangiopathy and was associated with significant time-dependent improvement in renal function in patients with atypical hemolytic-uremic syndrome.


  • C. M. Legendre
  • C. Licht
  • P. Muus
  • L. A. Greenbaum
  • S. Babu
  • C. Bedrosian
  • C. Bingham
  • D. J. Cohen
  • Y. Delmas
  • K. Douglas
  • F. Eitner
  • T. Feldkamp
  • D. Fouque
  • R. R. Furman
  • O. Gaber
  • M. Herthelius
  • M. Hourmant
  • Y. Lebranchu
  • C. Mariat
  • J. Menne
  • B. Moulin
  • J. Nuernberger
  • M. Ogawa
  • G. Remuzzi
  • T. Richard
  • R. Sberro-Soussan
  • B. Severino
  • N. S. Sheerin
  • A. Trivelli
  • L. B. Zimmerhackl
  • T. Goodship
  • C. Loirat
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Pediatrics
Original languageEnglish
Pages (from-to)2169-2181
JournalNew England Journal of Medicine
Issue number23
Publication statusPublished - 2013
Publication categoryResearch

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