Complement functional tests for monitoring eculizumab treatment in patients with atypical hemolytic uremic syndrome: an update
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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.
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.
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.
Monitoring complement activity allows a safe reduction in the frequency of ECU administration in aHUS while keeping the disease in remission.
KeywordsaHUS Maintenance Remission Eculizumab Complement activity
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.
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.
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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