[HTML][HTML] Terminal complement inhibitor eculizumab in adult patients with atypical hemolytic uremic syndrome: a single-arm, open-label trial

F Fakhouri, M Hourmant, JM Campistol… - American journal of …, 2016 - Elsevier
F Fakhouri, M Hourmant, JM Campistol, SR Cataland, M Espinosa, AO Gaber, J Menne
American journal of kidney diseases, 2016Elsevier
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 …
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.
Elsevier