TY - JOUR
T1 - Terminal Complement Inhibitor Eculizumab in Adult Patients with Atypical Hemolytic Uremic Syndrome
T2 - A Single-Arm, Open-Label Trial
AU - Fakhouri, Fadi
AU - Hourmant, Maryvonne
AU - Campistol, Josep M.
AU - Cataland, Spero R.
AU - Espinosa, Mario
AU - Gaber, A. Osama
AU - Menne, Jan
AU - Minetti, Enrico E.
AU - Provôt, François
AU - Rondeau, Eric
AU - Ruggenenti, Piero
AU - Weekers, Laurent E.
AU - Ogawa, Masayo
AU - Bedrosian, Camille L.
AU - Legendre, Christophe M.
N1 - Funding Information:
Support: This study was sponsored by Alexion Pharmaceuticals Inc, the manufacturer of eculizumab. The authors acknowledge Kenyon Ogburn, PhD, Erin Harvey, MS, and John F. Kincaid, MD, of Alexion Pharmaceuticals Inc and Kristen W. Quinn, PhD, of Peloton Advantage, LLC who provided medical writing/editorial support with funding from Alexion Pharmaceuticals Inc. The sponsor participated in study design, collection, analysis, and interpretation of data; writing the report; and the decision to submit the report for publication.
Publisher Copyright:
© 2016 The Authors.
PY - 2016/7/1
Y1 - 2016/7/1
N2 - 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.
AB - 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.
KW - Eculizumab
KW - Soliris
KW - TMA response
KW - adults
KW - atypical hemolytic uremic syndrome (aHUS)
KW - clinical trial
KW - hematologic normalization
KW - hemoglobin
KW - kidney disease
KW - lactate dehydrogenase (LDH)
KW - platelet count
KW - renal function
KW - terminal complement inhibitor
KW - thrombotic microangiopathy (TMA)
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U2 - 10.1053/j.ajkd.2015.12.034
DO - 10.1053/j.ajkd.2015.12.034
M3 - Article
C2 - 27012908
AN - SCOPUS:84975266700
SN - 0272-6386
VL - 68
SP - 84
EP - 93
JO - American Journal of Kidney Diseases
JF - American Journal of Kidney Diseases
IS - 1
ER -