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Lookup NU author(s): Andrew BryantORCiD, Jan Lecouturier, Giovany Orozco Leal, Dr Vicky Brocklebank, Dr Sonya Carnell, Dr Thomas ChadwickORCiD, Dr Sarah Dunn, Dr Sally Johnson, Professor David KavanaghORCiD, Dr Ciara Kennedy, Dr Michal Malina, Dr Emma Montgomery, Dr Colin Muirhead, Dr Yemi Oluboyede, Professor Luke ValeORCiD, Christopher Weetman, Professor Neil SheerinORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
Background: Atypical haemolytic uraemic syndrome is a rare disease (incidence: 0.4 cases per million per year) which, without treatment, is associated with high morbidity and mortality. Eculizumab, a monoclonal complement inhibitor, is an effective treatment but the optimal way to use this high-cost medication (£360,000 per year for an adult) has not been established. Objective: Establish the safety of eculizumab withdrawal and the effectiveness of a monitoring protocol to detect disease relapse and reintroduction of treatment if relapse occurs. Setting: Fifteen hospitals in the United Kingdom. Design: SETS aHUS is a multicentre, open label, prospective, single arm study of the safety and impact of eculizumab withdrawal in patients with atypical haemolytic uraemic syndrome using Bayes single arm analysis with a health economic analysis and qualitative study. Participants: Patients over 2 years of age with atypical haemolytic uraemic syndrome who were receiving eculizumab therapy for at least 6 months. Two study arms are described with 28 participants recruited to the withdrawal arm and 11 additional participants recruited to the standard of care arm of the study. Intervention: Withdrawal of eculizumab treatment and replacement with monitoring to assess disease activity with reintroduction of treatment if relapse occurs. Main outcome measures: The primary outcome measure was to determine the safety of eculizumab withdrawal in patients with atypical haemolytic uraemic syndrome during the 2-year study period. Patients met a primary outcome of 'safety event occurred' if there was a permanent reduction in estimated glomerular filtration rate or requirement for renal replacement therapy or significant extra-renal manifestation of disease. The health economic analysis compared the cost and health outcomes on and off eculizumab treatment. The qualitative study explored the experiences of patients on living with atypical haemolytic uraemic syndrome and eculizumab treatment, views on withdrawing from treatment and the proposed monitoring plan. Results: One of 28 patients (3.6%) who withdrew from treatment met a primary outcome. Based on the pre-study analysis plan, withdrawal from treatment is not associated with a greater risk to patients compared to remaining on treatment. Of 17 patients with an abnormality in complement regulation, 4 relapsed. Of 11 patients with no abnormality in complement regulation, 0 relapsed. It was possible, by monitoring and rapid patient access, to reintroduce eculizumab treatment when relapse was identified. Most patients welcomed the opportunity to withdraw from treatment but identified concerns about monitoring and the risk of relapse, informed by initial experience at presentation. Withdrawing a patient from treatment saves £4.2M in healthcare costs (80 years time horizon). Limitations: Reflecting the low prevalence, participant numbers are low, particularly in the standard of care group. Conclusions: Withdrawal of eculizumab treatment with monitoring of disease activity exhibited a favourable safety profile compared to continuation of eculizumab, was acceptable to patients and carers and is associated with significant cost savings. Future work: More real-world data should be generated by continued assessment of patients after treatment withdrawal including risk of relapse, renal outcomes, real-world economic analysis and a better understanding of communicating change to patients and carers. Funding: This synopsis presents independent research funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme as award number 15/130/94.Overall, 24 patients remained off eculizumab during their 2 years of trial participation. Four patients relapsed and eculizumab treatment was re-started. One patient’s kidney function fell, but overall withdrawing eculizumab had a similar safety profile as staying on treatment. The cause of atypical haemolytic uraemic syndrome predicted relapse. The quality of life of patients who withdrew from eculizumab is expected to increase, with minimal impact on life expectancy. We estimated that there would be a saving of £4,188,361 per patient who withdrew from treatment. In the interviews at the beginning of the trial, participants said that eculizumab treatment was disruptive to work and school. Eculizumab side-effects were also a problem. The decision not to withdraw from eculizumab was based upon concerns about the possibility of relapse. At the end of the trial, participants said that the extreme tiredness and other symptoms associated with eculizumab were no longer present with less disruption to their daily lives. Anxiety was an issue, but this became less over time. Knowing they could restart eculizumab immediately was reassuring. The following future research is important: (1) Can eculizumab be withdrawn again in patients who have relapsed? (2) What are the factors influencing risk of relapse? (3) What is the most effective way to manage patients short and long-term after withdrawal of eculizumab? It will be critical to identify what resources are required to implement new ways to manage atypical haemolytic uraemic syndrome.
Author(s): Bryant A, Lecouturier J, Orozco-Leal G, Brocklebank V, Carnell S, Chadwick TJ, Dunn S, Johnson SA, Kavanagh D, Kennedy CA, Malina M, Montgomery EK, Muirhead CR, Oluboyede Y, Vale L, Weetman C, Kwan Soon Wong E, Woodward L, Sheerin NS
Publication type: Article
Publication status: Published
Journal: Health Technology Assessment
Year: 2026
Volume: 30
Issue: 20
Pages: 1-37
Online publication date: 01/02/2026
Acceptance date: 02/04/2018
Date deposited: 16/03/2026
ISSN (electronic): 2046-4924
Publisher: National Institute for Health and Care Research
URL: https://doi.org/10.3310/GJNS4701
DOI: 10.3310/GJNS4701
Data Access Statement: All data requests should be submitted to the corresponding author for consideration. Access to anonymised data may be granted following review.
PubMed id: 41772879
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