Individualised therapeutic approach to the patient with atypical haemolytic-uraemic syndrome

Atypical haemolytic-uraemic syndrome (aHUS) is a rare disease associated with uncontrolled activation of the alternative complement pathway, leading to thrombotic microangiopathy (TMA). Early diagnosis and treatment with eculizumab, a monoclonal antibody targeting the complement component C5, are cr...

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Main Authors: Ivana Mikačić, Nikolina Marić
Format: Article
Language:English
Published: Elsevier 2024-11-01
Series:Clinical Medicine
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Online Access:http://www.sciencedirect.com/science/article/pii/S1470211824054356
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author Ivana Mikačić
Nikolina Marić
author_facet Ivana Mikačić
Nikolina Marić
author_sort Ivana Mikačić
collection DOAJ
description Atypical haemolytic-uraemic syndrome (aHUS) is a rare disease associated with uncontrolled activation of the alternative complement pathway, leading to thrombotic microangiopathy (TMA). Early diagnosis and treatment with eculizumab, a monoclonal antibody targeting the complement component C5, are crucial to improve outcomes and prevent renal failure and mortality. Current recommendations include lifelong eculizumab therapy, yet this practice presents challenges including high treatment costs and increased infection risks from prolonged complement inhibition. We hypothesise that a personalised eculizumab dosing strategy tailored to individual patient responses could optimise therapy, reduce costs and improve safety. This hypothesis was evaluated through a presentation of a patient who was managed with a specific eculizumab treatment approach. The patient’s condition improved significantly, allowing for a gradual reduction in eculizumab dosage based on clinical response and drug level monitoring.Throughout treatment, the patient’s complement activity and eculizumab levels were closely monitored, showing that lower doses maintained therapeutic efficacy without evident TMA recurrence. This case supports the feasibility of transitioning from fixed regimens to personalised dosing strategies in managing aHUS. Such approaches could mitigate the risks and costs associated with lifelong therapy while maintaining disease control, especially considering the variability in relapse risk among different genetic mutations. This personalised treatment model might significantly impact the management of aHUS, aligning clinical care with individual patient needs and economic considerations. Further research should relate drug pharmacokinetics/pharmacodynamics to clinical/genetic setting to identify milestones of individual patient treatment approach.
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spelling doaj-art-23caeff6e83e4d8fad6f099ff3aff1ff2025-08-20T02:06:57ZengElsevierClinical Medicine1470-21182024-11-0124610025010.1016/j.clinme.2024.100250Individualised therapeutic approach to the patient with atypical haemolytic-uraemic syndromeIvana Mikačić0Nikolina Marić1Department of Internal Medicine, Unit for Clinical Pharmacology, University Hospital ‘Sveti Duh’, Sveti Duh 64, Zagreb, Croatia; Department of Internal Medicine, School of Medicine, University of Zagreb, Šalata 3, 10000 Zagreb, Croatia; Corresponding author at: University Hospital ‘Sveti Duh’, Sveti Duh 64, 10000 Zagreb, Croatia.Department of Internal Medicine, School of Medicine, University of Zagreb, Šalata 3, 10000 Zagreb, Croatia; Department of Internal Medicine, Unit for Intensive Care, University Hospital ‘Sveti Duh’, Sveti Duh 64, Zagreb, CroatiaAtypical haemolytic-uraemic syndrome (aHUS) is a rare disease associated with uncontrolled activation of the alternative complement pathway, leading to thrombotic microangiopathy (TMA). Early diagnosis and treatment with eculizumab, a monoclonal antibody targeting the complement component C5, are crucial to improve outcomes and prevent renal failure and mortality. Current recommendations include lifelong eculizumab therapy, yet this practice presents challenges including high treatment costs and increased infection risks from prolonged complement inhibition. We hypothesise that a personalised eculizumab dosing strategy tailored to individual patient responses could optimise therapy, reduce costs and improve safety. This hypothesis was evaluated through a presentation of a patient who was managed with a specific eculizumab treatment approach. The patient’s condition improved significantly, allowing for a gradual reduction in eculizumab dosage based on clinical response and drug level monitoring.Throughout treatment, the patient’s complement activity and eculizumab levels were closely monitored, showing that lower doses maintained therapeutic efficacy without evident TMA recurrence. This case supports the feasibility of transitioning from fixed regimens to personalised dosing strategies in managing aHUS. Such approaches could mitigate the risks and costs associated with lifelong therapy while maintaining disease control, especially considering the variability in relapse risk among different genetic mutations. This personalised treatment model might significantly impact the management of aHUS, aligning clinical care with individual patient needs and economic considerations. Further research should relate drug pharmacokinetics/pharmacodynamics to clinical/genetic setting to identify milestones of individual patient treatment approach.http://www.sciencedirect.com/science/article/pii/S1470211824054356Atypical haemolytic-uremic syndromeEculizumabComplement inhibitionGenetic testing
spellingShingle Ivana Mikačić
Nikolina Marić
Individualised therapeutic approach to the patient with atypical haemolytic-uraemic syndrome
Clinical Medicine
Atypical haemolytic-uremic syndrome
Eculizumab
Complement inhibition
Genetic testing
title Individualised therapeutic approach to the patient with atypical haemolytic-uraemic syndrome
title_full Individualised therapeutic approach to the patient with atypical haemolytic-uraemic syndrome
title_fullStr Individualised therapeutic approach to the patient with atypical haemolytic-uraemic syndrome
title_full_unstemmed Individualised therapeutic approach to the patient with atypical haemolytic-uraemic syndrome
title_short Individualised therapeutic approach to the patient with atypical haemolytic-uraemic syndrome
title_sort individualised therapeutic approach to the patient with atypical haemolytic uraemic syndrome
topic Atypical haemolytic-uremic syndrome
Eculizumab
Complement inhibition
Genetic testing
url http://www.sciencedirect.com/science/article/pii/S1470211824054356
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