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Saftey and impact of eculizumab withdrawal in patients with atypical haemolytic uraemic syndrome: protocol for a multicentre, open-label, prospective, single-arm study

Lookup NU author(s): Dr Sarah Dunn, Dr Vicky Brocklebank, Andrew Bryant, Dr Thomas Chadwick, Dr Sally Johnson, Professor David KavanaghORCiD, Jan Lecouturier, Dr Michal Malina, Eoin Moloney, Dr Yemi Oluboyede, Christopher Weetman, Dr Edwin Wong, Professor Neil SheerinORCiD

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Abstract

ABSTRACT Introduction Atypical haemolytic uraemic syndrome (aHUS) is a rare, life threatening disease caused by excessive activation of part of the immune system called complement. Eculizumab is an effective treatment, controlling aHUS in 90% of patients. Due to the risk of relapse, lifelong treatment is currently recommended. Eculizumab treatment is not without problems, foremost being the risk of severe meningococcal infection, the burden of bi-weekly intravenous injections and the high cost. This paper describes the design of the Stopping Eculizumab Treatment Safely in aHUS (SETS aHUS) trial that aims to establish whether a safety monitoring protocol, including the reintroduction of Eculizumab for those who relapse, could be a safe, alternative treatment strategy for patients with aHUS. Methods and analysis This is a multi-centre, non-randomised, open label study of Eculizumab withdrawal with continuous monitoring of thrombotic microangiopathy (TMA) related serious adverse events using the Bayes factor single arm design. 30 patients will be recruited to withdraw from Eculizumab and have regular blood and urine tests for 24 months, to monitor for disease activity. If relapse occurs, treatment will be restarted within 24 hours of presentation. 20 patients will remain on treatment and complete health economic questionnaires only. An embedded qualitative study will explore the views of participants. Ethics and dissemination A favourable ethical opinion and approval was obtained from the North East - Tyne & Wear South Research Ethics Committee. Outcomes will be disseminated via peer-reviewed articles and conference presentations. Trial registration EudraCT Number: 2017-003916-37 ISRCTN number: ISRCTN17503205 Date of Registration: 20 April 2018 Keywords atypical Haemolytic Uraemic Syndrome, qualitative research, Complement, Eculizumab Article summary Strengths and limitations of this study This is the first UK trial to evaluate the safety of eculizumab withdrawal in patient with aHUS.This trial fulfils the NICE recommendation that a research programme, with robust methods, should be carried out to evaluate when stopping Eculizumab treatment or dose adjustment might occur. · Clinical experience suggests if relapse occurs this will likely happen in the first 12 months of withdrawal however, this trial follows patients up for 24 months to capture those patients who may relapse after the 12-month point. · The small number of aHUS patients on treatment in the UK is insufficient to conduct a standard parallel group, randomised controlled trial. · COVID-19 has had an impact on recruitment. Trial Status This manuscript is based upon trial protocol version 7.0 dated 14th January 2021. The first patient was recruited in November 2018, recruitment ended on 31st January 2022 and planned last patient visit is November 2023.


Publication metadata

Author(s): Dunn S, Brocklebank V, Bryant A, Carnell S, Chadwick TJ, Johnson S, Kavannagh D, Lecouturier J, Malina M, Moloney E, Oluboyede Y, Weetman C, Wong EKS, Woodward L, Sheerin NS

Publication type: Article

Publication status: Published

Journal: BMJ Open

Year: 2022

Volume: 12

Online publication date: 19/09/2022

Acceptance date: 18/08/2022

ISSN (electronic): 2044-6055

Publisher: BMJ Publishing Group

URL: https://doi.org/10.1136/bmjopen-2021-054536

DOI: 10.1136/bmjopen-2021-054536


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