Gianluigi Ardissino1, Francesca Tel2, Martina Sgarbanti3, Donata Cresseri4, Antenore Giussani5, Samantha Griffini6, Elena Grovetto6, Ilaria Possenti2, Michela Perrone2, Sara Testa3, Fabio Paglialonga3, Piergiorgio Messa4, Massimo Cugno6. 1. Center for HUS Prevention, Control and Management at the Pediatric and Dialysis Unit, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, v. Commenda, 9, 20122, Milan, Italy. ardissino@centroseu.org. 2. Center for HUS Prevention, Control and Management at the Pediatric and Dialysis Unit, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, v. Commenda, 9, 20122, Milan, Italy. 3. Center for HUS Prevention, Control and Management at the Molecular Biology Laboratory, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy. 4. Center for HUS Prevention, Control and Management at the Nephrology Unit, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy. 5. Center for HUS Prevention, Control and Management at the Kidney Transplant Unit, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy. 6. Center for HUS Prevention, Control, and Management at Medicina Interna, Dipartimento di Fisiopatologia Medico-Chirurgica e dei Trapianti, Università degli Studi di Milano, Milan, Italy.
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.
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.
Authors: M Cugno; R Gualtierotti; I Possenti; S Testa; F Tel; S Griffini; E Grovetti; S Tedeschi; S Salardi; D Cresseri; P Messa; G Ardissino Journal: J Thromb Haemost Date: 2014-07-16 Impact factor: 5.824
Authors: Elena B Volokhina; Nicole C A J van de Kar; Grethe Bergseth; Thea J A M van der Velden; Dineke Westra; Jack F M Wetzels; Lambertus P van den Heuvel; Tom Eirik Mollnes Journal: Clin Immunol Date: 2015-06-23 Impact factor: 3.969
Authors: C M Legendre; C Licht; P Muus; L A Greenbaum; S Babu; C Bedrosian; C Bingham; D J Cohen; Y Delmas; K Douglas; F Eitner; T Feldkamp; D Fouque; R R Furman; O Gaber; M Herthelius; M Hourmant; D Karpman; Y Lebranchu; C Mariat; J Menne; B Moulin; J Nürnberger; M Ogawa; G Remuzzi; T Richard; R Sberro-Soussan; B Severino; N S Sheerin; A Trivelli; L B Zimmerhackl; T Goodship; C Loirat Journal: N Engl J Med Date: 2013-06-06 Impact factor: 91.245
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Authors: Timothy H J Goodship; H Terence Cook; Fadi Fakhouri; Fernando C Fervenza; Véronique Frémeaux-Bacchi; David Kavanagh; Carla M Nester; Marina Noris; Matthew C Pickering; Santiago Rodríguez de Córdoba; Lubka T Roumenina; Sanjeev Sethi; Richard J H Smith Journal: Kidney Int Date: 2016-12-16 Impact factor: 10.612
Authors: Marta Palomo; Miquel Blasco; Patricia Molina; Miquel Lozano; Manuel Praga; Sergi Torramade-Moix; Julia Martinez-Sanchez; Joan Cid; Gines Escolar; Enric Carreras; Cristina Paules; Fatima Crispi; Luis F Quintana; Esteban Poch; Lida Rodas; Emma Goma; Johann Morelle; Mario Espinosa; Enrique Morales; Ana Avila; Virginia Cabello; Gema Ariceta; Sara Chocron; Joaquin Manrique; Xoana Barros; Nadia Martin; Ana Huerta; Gloria M Fraga-Rodriguez; Mercedes Cao; Marisa Martin; Ana Maria Romera; Francesc Moreso; Anna Manonelles; Eduard Gratacos; Arturo Pereira; Josep M Campistol; Maribel Diaz-Ricart Journal: Clin J Am Soc Nephrol Date: 2019-11-06 Impact factor: 8.237