Abstract: TH-PO1201
Stopping Eculizumab Treatment Safely in Atypical Haemolytic Uraemic Syndrome (SETS aHUS): A Multicentre, Open-Label, Prospective, Single-Arm Trial of the Safety and Impact of Eculizumab Withdrawal
Session Information
- Late-Breaking Science Posters
October 24, 2024 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Genetic Diseases of the Kidneys
- 1202 Genetic Diseases of the Kidneys: Non-Cystic
Authors
- Sheerin, Neil S., Newcastle University, Newcastle upon Tyne, United Kingdom
- Johnson, Sally A., Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, United Kingdom
- Wong, Edwin Kwan Soon, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, United Kingdom
- Vale, Luke, London School of Hygiene & Tropical Medicine, London, United Kingdom
- Malina, Michal, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, United Kingdom
- Orozco Leal, Giovany, Newcastle University, Newcastle upon Tyne, Tyne and Wear, United Kingdom
- Kennedy, Ciara Anne-Marie, Newcastle University, Newcastle upon Tyne, Tyne and Wear, United Kingdom
- Dunn, Sarah, Newcastle University, Newcastle upon Tyne, Tyne and Wear, United Kingdom
- Kavanagh, David, Newcastle University, Newcastle upon Tyne, United Kingdom
Background
Atypical Haemolytic Uraemic Syndrome (aHUS) is a rare disease 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 has not been determined. The SETS aHUS trial aimed to establish the safety of eculizumab withdrawal and the effectiveness of a monitoring protocol to detect disease relapse and safe reintroduction of treatment if disease relapse occurs.
Methods
The SETS aHUS multicentre, open label, prospective, single arm trial enrolled participants from 15 UK hospitals with embedded qualitative and health economic analyses. Patients over two years of age with aHUS who were receiving eculizumab therapy for at least six months were eligible to withdraw from treatment, replacing it with monitoring to assess disease activity with re-introduction of treatment if relapse occurred. The primary outcome measure was harm to a participant as a consequence of eculizumab withdrawal during the 2-year trial period. Participants met a primary outcome if there was a permanent reduction in estimated glomerular filtration rate (GFR), requirement for kidney replacement therapy or significant extra-renal manifestation of disease. The Bayes factor single arm binary model was used to monitor and analyse the trial data, applying pre-trial stopping rules. The trial is registered with the European Union Drug Regulating Authority (EudraCT 2017-003916-37).
Results
One of 28 participants (3.6%) who withdrew from treatment met a primary outcome. Four participants relapsed, all with pathogenic genetic variants in complement proteins. Only participants with an identified cause of complement dysregulation relapsed. It was possible, by monitoring and rapid participant access, to successfully reintroduce eculizumab treatment. Based on the pre-trial analysis plan, withdrawal from treatment is not associated with a greater risk to patients compared to remaining on treatment.
Conclusion
Withdrawal of eculizumab treatment with monitoring of disease activity was not associated with an increased risk of harm compared to continuation of eculizumab.
Funding
- Government Support - Non-U.S.