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Am J Kidney Dis. 2016 Jul;68(1):84-93. doi: 10.1053/j.ajkd.2015.12.034. Epub 2016 Mar 21.

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

Author information

1
Department of Nephrology and Immunology, UMR 643, CHU de Nantes, Nantes, France. Electronic address: fadi.fakhouri@univ-nantes.fr.
2
Department of Nephrology and Immunology, UMR 643, CHU de Nantes, Nantes, France.
3
Nephrology and Urology Department, Hospital Clinic, University of Barcelona, Barcelona, Spain.
4
Division of Hematology, The Ohio State University Medical Center, Columbus, OH.
5
Nefrología, Hospital Universitario Reina Sofía, Córdoba, Spain.
6
Houston Methodist Research Institute, Houston, TX.
7
Clinic for Nephrology and Hypertension, Hannover Medical School, Hannover, Germany.
8
Division of Nephrology, Careggi University Hospital, Florence, Italy.
9
Department of Nephrology, CHU Lille, Lille, France.
10
Urgences Néphrologiques et Transplantation Rénale, Hôpital Tenon and Université Paris VI, Paris, France.
11
IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Centro Anna Maria Astori, Bergamo, Italy.
12
Service of Nephrology, Dialysis and Transplantation, Centre Hospitalier Universitaire, Liège, Belgium.
13
Alexion Pharmaceuticals, Inc, Cheshire, CT.
14
Adult Kidney Transplant Unit, Université Paris Descartes and Hôpital Necker, Paris, France.

Abstract

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 × 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.

INTERVENTION:

Intravenous eculizumab (900mg/wk for 4 weeks, 1,200mg 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 × 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.

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.

KEYWORDS:

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)

PMID:
27012908
DOI:
10.1053/j.ajkd.2015.12.034
[Indexed for MEDLINE]
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