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

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<150x10(3)/mu L, hemoglobin <= lower limit of normal, lactate dehydrogenase >= 1.5 x 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 x 10(3) /mu L, 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/plasmainfusion 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. Am J Kidney Dis. 68(1): 84-93. (C) 2016 The Authors. Published by Elsevier Inc. on behalf of the National Kidney Foundation, Inc. This is an open access article under the CC BY-NC-ND license.