Authors' objectives: 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. Establish the safety of eculizumab withdrawal and the effectiveness of a monitoring protocol to detect disease relapse and reintroduction of treatment if relapse occurs.

Authors' results and conclusions: 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). 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.

Authors' methods: Fifteen hospitals in the United Kingdom. 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. 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. 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. Reflecting the low prevalence, participant numbers are low, particularly in the standard of care group.

Project Status: Completed

URL for project: https://www.journalslibrary.nihr.ac.uk/programmes/hta/NIHR136061

Year Published: 2026

URL for published report: https://www.journalslibrary.nihr.ac.uk/hta/GJNS4701

URL for additional information: English

English language abstract: An English language summary is available

Publication Type: Full HTA

Country: England, United Kingdom

DOI: 10.3310/GJNS4701

Organisation Name: NIHR Health Technology Assessment programme

Contact Address: NIHR Journals Library, National Institute for Health and Care Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK

Contact Name: journals.library@nihr.ac.uk

Contact Email: journals.library@nihr.ac.uk