• 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, and Christophe M Legendre.
• Department of Nephrology and Immunology, UMR 643, CHU de Nantes, Nantes, France. Electronic address: fadi.fakhouri@univ-nantes.fr.
• Am. J. Kidney Dis. 2016 Jul 1; 68 (1): 84-93.

BackgroundAtypical 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 DesignOpen-label single-arm phase 2 trial.Setting & ParticipantsPatients 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.InterventionIntravenous eculizumab (900mg/wk for 4 weeks, 1,200mg at week 5 and then every 2 weeks) for 26 weeks.Outcomes & MeasurementsPrimary 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.Results41 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.LimitationsSingle-arm open-label design.ConclusionsResults highlight the benefits of eculizumab in adult patients with aHUS: improvement in hematologic, renal, and quality-of-life parameters; dialysis discontinuation; and transplant protection.Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

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