Complement functional tests for monitoring eculizumab treatment in patients with atypical hemolytic uremic syndrome.
BACKGROUND
Atypical hemolytic uremic syndrome (aHUS) is a thrombotic microangiopathy characterized by hemolysis, platelet consumption, and renal injury. Eculizumab, a mAb that blocks complement activity, has been successfully used in aHUS.


OBJECTIVE
To optimize eculizumab therapy in aHUS patients by monitoring complement functional tests and markers of disease activity.


METHODS
We studied 18 patients with aHUS (10 males; eight females; age range, 2-40 years) treated with eculizumab to induce and/or maintain disease remission. Patients were followed up for a cumulative observation period of 160 months, during which blood samples were obtained at various time intervals to measure complement activity (Wieslab for the classical, alternative and mannose-binding lectin complement pathways) and the parameters of disease activity (haptoglobin and lactate dehydrogenase serum levels, and platelet count). The intravenous eculizumab doses of 12-33 mg kg(-1) were initially administered every week, with the interval between doses being gradually extended to 2 weeks, 3 weeks and 4 weeks on the basis of strict laboratory and clinical control.


RESULTS
Complement activity was normal before eculizumab treatment, regardless of the state of the disease (activity or remission). It was completely suppressed 1 week, 2 weeks and 3 weeks after the last eculizumab infusion (mean values ± standard deviation: 1% ± 1% to 3% ± 5% for both the classical and alternative pathways; P = 0.0001 vs. baseline), and partially suppressed after 4 weeks (22% ± 26% and 16% ± 27%; P = 0.0001 vs. baseline). The increase in the time interval between eculizumab infusions did not change disease activity markers.


CONCLUSIONS
Monitoring complement tests can allow a safe reduction in the frequency of eculizumab administration in aHUS while keeping the disease in remission.
Medicina Interna, Dipartimento di Fisiopatologia Medico-Chirurgica e dei Trapianti, Università degli Studi di Milano, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy.
M
M
Cugno
R
R
Gualtierotti
I
I
Possenti
S
S
Testa
F
F
Tel
S
S
Griffini
E
E
Grovetti
S
S
Tedeschi
S
S
Salardi
D
D
Cresseri
P
P
Messa
G
G
Ardissino
D000293:Adolescent; D000328:Adult; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D065766:Atypical Hemolytic Uremic Syndrome / Q000188:drug therapy* / Q000235:genetics; D001792:Blood Platelets / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D003176:Complement C3 / Q000037:antagonists & inhibitors* / Q000737:chemistry; D003182:Complement C5 / Q000037:antagonists & inhibitors* / Q000737:chemistry; D017242:Complement Factor H / Q000737:chemistry; D005260:Female; D006461:Hemolysis; D006801:Humans; D016030:Kidney Transplantation; D008297:Male; D009154:Mutation; D010976:Platelet Count; D012074:Remission Induction; D057049:Thrombotic Microangiopathies / Q000188:drug therapy; D013997:Time Factors; D055815:Young Adult
D061067:Antibodies, Monoclonal, Humanized; D003176:Complement C3; D003182:Complement C5; D017242:Complement Factor H; C481642:eculizumab
atypical hemolytic uremic syndrome; complement; complement component 5; eculizumab; thrombotic microangiopathies