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. Objectives: To optimize eculizumab therapy in aHUS patients by monitoring complement functional tests and markers of disease activity. Patients/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.

Complement functional tests for monitoring eculizumab treatment in patients with atypical hemolytic uremic syndrome / M. Cugno, R. Gualtierotti, I. Possenti, S. Testa, F. Tel, S. Griffini, E. Grovetti, S. Tedeschi, S. Salardi, D. Cresseri, P. Messa, G. Ardissino. - In: JOURNAL OF THROMBOSIS AND HAEMOSTASIS. - ISSN 1538-7933. - 12:9(2014), pp. 1440-1448. [10.1111/jth.12615]

Complement functional tests for monitoring eculizumab treatment in patients with atypical hemolytic uremic syndrome

M. Cugno;R. Gualtierotti;F. Tel;S. Salardi;P. Messa;
2014

Abstract

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. Objectives: To optimize eculizumab therapy in aHUS patients by monitoring complement functional tests and markers of disease activity. Patients/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.
Atypical hemolytic uremic syndrome; Complement; Complement component 5; Eculizumab; Thrombotic microangiopathies
Settore MED/09 - Medicina Interna
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
Article (author)
File in questo prodotto:
File Dimensione Formato  
JTH-2014.pdf

non disponibili

Tipologia: Publisher's version/PDF
Dimensione 632.38 kB
Formato Adobe PDF
632.38 kB Adobe PDF   Visualizza/Apri   Richiedi una copia
Pubblicazioni consigliate

Caricamento pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/253543
Citazioni
  • ???jsp.display-item.citation.pmc??? 29
  • Scopus 73
  • ???jsp.display-item.citation.isi??? 70
social impact