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Comparative efficacy of ravulizumab and eculizumab in the treatment of atypical hemolytic uremic syndrome: an indirect comparison using clinical trial data

Lookup NU author(s): Professor Neil SheerinORCiD



This is the authors' accepted manuscript of an article that has been published in its final definitive form by Dustri-Verlag, 2022.

For re-use rights please refer to the publisher's terms and conditions.


Ravulizumab and eculizumab are approved terminal complement inhibitor treatments for atypical hemolytic uremic syndrome (aHUS). Ravulizumab was engineered from eculizumab to have an increased half-life allowing for reduced dosing frequency (8-weekly versus 2-weekly). To account for differences in respective clinical trials, a validated balancing technique was used to enable an indirect comparison of ravulizumab and eculizumab treatment efficacy in aHUS. Patient-level data from four eculizumab clinical trials were available for pooling and comparison with data from two ravulizumab trials. In the primary analysis, adult native kidney data were compared. Propensity scores were calculated from baseline characteristics (dialysis status, estimated glomerular filtration rate, platelet count, serum lactate dehydrogenase). Stabilized inverse probability weighting was used to balance groups. Changes in outcomes from baseline to 26 weeks were compared between treatment groups. Sensitivity and subgroup analyses were conducted to assess the robustness of findings. Overall, 85 patients (46 ravulizumab, 39 eculizumab) were included in the primary analysis. Demographic and clinical characteristics were well balanced after weighting at baseline. At 26 weeks, clinical outcomes (including renal function, hematological markers and dialysis prevalence) and fatigue and quality of life measures were improved with eculizumab and ravulizumab treatment. No differences between treatment groups reached statistical significance, although confidence intervals were wide. Sensitivity and subgroup analysis results were consistent with those of the primary analysis. Using appropriate methodology for indirect comparison of studies, no differences in outcomes were seen between ravulizumab and eculizumab although, owing to small sample sizes, confidence intervals were wide.

Publication metadata

Author(s): Tomazos I, Hatswell AJ, Cataland S, Chen P, Freemantle N, Lommele A, Deighton K, Knowles E, Sheerin NS, Rondeau E

Publication type: Article

Publication status: Published

Journal: Clinical Nephrology

Year: 2022

Volume: 97

Pages: 261-272

Print publication date: 01/05/2022

Online publication date: 21/12/2021

Acceptance date: 15/09/2021

Date deposited: 28/09/2021

ISSN (electronic): 0301-0430

Publisher: Dustri-Verlag


DOI: 10.5414/CN110516


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