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Pediatric Nephrology

, Volume 33, Issue 3, pp 457–461 | Cite as

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

  • Gianluigi Ardissino
  • Francesca Tel
  • Martina Sgarbanti
  • Donata Cresseri
  • Antenore Giussani
  • Samantha Griffini
  • Elena Grovetto
  • Ilaria Possenti
  • Michela Perrone
  • Sara Testa
  • Fabio Paglialonga
  • Piergiorgio Messa
  • Massimo Cugno
Original Article

Abstract

Background

Atypical hemolytic uremic syndrome (aHUS) is a thrombotic microangiopathy (TMA) characterized by platelet consumption, hemolysis, and organ damage. Eculizumab (ECU), a humanized antibody that blocks complement activity, has been successfully used in aHUS, but the best treatment schedule is not yet clear.

Methods

Here, we report our experience with ECU maintenance treatment and the interval between subsequent doses being extended based on global classical complement pathway (CCP) activity aimed at <30% for maintaining aHUS into remission.

Results

We report on 38 patients with aHUS, 13 children, 21 female, with a median age of 25.0 years (range 0.5–60) at disease onset treated with ECU standard schedule for a median of 2.6 months (range 0.4–24.6). Once stable TMA remission was obtained, the interval between ECU doses was extended based on complement function, with a target CCP activity of <30%. With this approach, 22 patients regularly receive ECU infusion every 28 days and 16 every 21. During a median observation period on ECU, an extended interval of 26.9 months (range 0.8–80.9), with a cumulative observation period of 1,208 months, none of the patients relapsed.

Conclusion

Monitoring complement activity allows a safe reduction in the frequency of ECU administration in aHUS while keeping the disease in remission.

Keywords

aHUS Maintenance Remission Eculizumab Complement activity 

Notes

Acknowledgements

We are grateful to the following physicians, whose collaboration in the management of patients was essential: B. Basolo (Torino), M. Belingheri (Milan), F. Bertola (Legnano), A. Castiglioni (Busto Arsizio), G. Colussi (Milan), L. Costantini (Vercelli), R. Cravero (Biella), M. D’Amico (Como), L. Del Vecchio (Lecco), F. Catalano (Reggio Calabria), P. Fabbrini (Monza), A. Inzoli (Crema), S. Marenghini (Palermo), M. martini (Arezzo), C. Milocco (Monfalcone), L. Morabito (Imperia), A. Naticchia (Rome), F. Paglialonga (Milan), A. Pani (Cagliari), L. Potenza (Modena), A. Rigotti (Rimini), S. Testa (Milan), and G. Visconti (Palermo). We are also grateful to “Progetto ALICE ONLUS. Associazione per la Lotta alla SEU” for their continuous and precious support. We thank “Progetto ALICE ONLUS. Associazione per la lotta alla SEU” for their continuous and precious support.

Contributions

Research idea and study design: GA, DC, MC; data acquisition: GA, DC, MC, FT, MP, MS, IP, SG, AG; data analysis/interpretation: GA, FT, MC, SG, MP, IP; statistical analysis: GA, MC, AG. MS; supervision or mentorship: AG, MC, DC. Each author contributed important intellectual content during manuscript drafting or revision and accepts accountability for the overall work by ensuring that questions pertaining to the accuracy or integrity of any portion of the work are appropriately investigated and resolved. GA takes responsibility that this study has been reported honestly, accurately, and transparently; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained.

Funding

This study was supported by a research grant provided by “Progetto ALICE ONLUS—Associazione per la Lotta alla SEU.”

Compliance with ethical standards

Conflicts of interest

D. Cresseri: national (Italy) coordinator of the Global aHUS Registry supported by Alexion Pharmaceuticals, Inc.; G. Ardissino: member of the scientific advisory board of the Global aHUS Registry supported by Alexion Pharmaceuticals, Inc. The other authors state that they have no conflicts of interest.

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Copyright information

© IPNA 2017

Authors and Affiliations

  • Gianluigi Ardissino
    • 1
  • Francesca Tel
    • 1
  • Martina Sgarbanti
    • 2
  • Donata Cresseri
    • 3
  • Antenore Giussani
    • 4
  • Samantha Griffini
    • 5
  • Elena Grovetto
    • 5
  • Ilaria Possenti
    • 1
  • Michela Perrone
    • 1
  • Sara Testa
    • 2
  • Fabio Paglialonga
    • 2
  • Piergiorgio Messa
    • 3
  • Massimo Cugno
    • 5
  1. 1.Center for HUS Prevention, Control and Management at the Pediatric and Dialysis UnitFondazione IRCCS Ca’ Granda, Ospedale Maggiore PoliclinicoMilanItaly
  2. 2.Center for HUS Prevention, Control and Management at the Molecular Biology LaboratoryFondazione IRCCS Ca’ Granda, Ospedale Maggiore PoliclinicoMilanItaly
  3. 3.Center for HUS Prevention, Control and Management at the Nephrology UnitFondazione IRCCS Ca’ Granda, Ospedale Maggiore PoliclinicoMilanItaly
  4. 4.Center for HUS Prevention, Control and Management at the Kidney Transplant UnitFondazione IRCCS Ca’ Granda, Ospedale Maggiore PoliclinicoMilanItaly
  5. 5.Center for HUS Prevention, Control, and Management at Medicina Interna, Dipartimento di Fisiopatologia Medico-Chirurgica e dei TrapiantiUniversità degli Studi di MilanoMilanItaly

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