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Eculizumab treatment in atypical hemolytic uremic syndrome: correlation between functional complement tests and drug levels

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Abstract

Background

Atypical hemolytic uremic syndrome (aHUS) is characterized by platelet consumption, hemolysis, and renal injury. Eculizumab, a humanized antibody that blocks complement activity, has been successfully used in aHUS, but the best treatment schedule has not yet been clearly defined.

Methods

Herein we report our experience with eculizumab maintenance treatment, in which the interval between subsequent doses was adjusted based on classical complement pathway (CCP) activity, targeted to < 30% for the prevention of relapses. Trough circulating levels of free eculizumab were determined by an immunoenzymatic method. Genetic and serologic characteristics of the patients were also assessed.

Results

We report on 38 patients with aHUS with a median age of 25.0 years (range 0.5–60.0 years) treated with eculizumab. Once stable disease remission was obtained, the interval between eculizumab doses was extended based on target CCP activity. With this approach, presently, 22 patients regularly receive eculizumab infusion every 28 days and 16 receive it every 21. During a median observation period of 32.3 months (range 4.0–92.4 months) and a cumulative period of 1295 months, no patient relapsed. An inverse correlation between CCP activity and eculizumab circulating levels was present (r = − 0.690, p = 0.0001), with CCP activity being inhibited as long as free eculizumab was measurable in serum.

Conclusions

In patients with aHUS on eculizumab maintenance treatment, complement activity measurement can be used as a proxy for circulating levels of the drug. Monitoring complement activity allows for safe tailoring of the frequency of eculizumab administration, thus avoiding excessive drug exposure while keeping the disease in remission.

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Availability of data and material

The datasets generated and/or analyzed during the current study are available from the corresponding author on reasonable request.

Code availability

Not applicable.

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Acknowledgements

The authors are grateful to “Progetto Alice Onlus, Associazione per la lotta alla Sindrome Emolitico Uremica” for the valuable support provided to perform this study.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Author information

Authors and Affiliations

  1. Medicina Interna, Dipartimento di Fisiopatologia Medico-Chirurgica e dei Trapianti, Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, Università Degli Studi di Milano, Via Pace, 9, 20122, Milano, Italy

    Massimo Cugno, Samantha Griffini & Elena Grovetti

  2. Center for HUS Prevention, Control and Management at Pediatric Nephrology, Dialysis and Transplant Unit, Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, Milano, Italy

    Valentina Capone & Gianluigi Ardissino

  3. Medical Genetics Laboratory, Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, Milano, Italy

    Giulia Pintarelli & Luigi Porcaro

  4. Department of Biomedical and Clinical Sciences “L. Sacco”, Unit of Clinical Pharmacology, Luigi Sacco University Hospital, ASST Fatebenefratelli-Sacco, Università Degli Studi di Milano, Milano, Italy

    Emilio Clementi

Authors
  1. Massimo Cugno
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  2. Valentina Capone
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  3. Samantha Griffini
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  4. Elena Grovetti
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  5. Giulia Pintarelli
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  6. Luigi Porcaro
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  7. Emilio Clementi
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  8. Gianluigi Ardissino
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Contributions

Designed the study MC and GA. Collected clinical data MC, VC and GA. Performed biological analyses SG, EG, GP, and LP. Designed and performed statistical analyses MC, EC and GA. Drafted the initial version of the manuscript MC and GA. Revised the manuscript critically for intellectual content MC, VC, SG, EG, GP, LP, EC and GA. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Massimo Cugno.

Ethics declarations

Conflict of interest

G. Ardissino reports consultancy agreements with Alexion and Alnylam; scientific advisory board membership with Alexion Inc. All remaining authors have no relevant financial or non-financial interests to disclose.

Ethical approval

The study was approved by the local review board and was conducted according to the ethical principles contained in the 2013 revision of the Declaration of Helsinki and the code of Good Clinical Practice.

Consent to participate

Written informed consent was obtained from all individual adult participants and from the parents of pediatric patients included in the study.

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Not applicable.

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Cugno, M., Capone, V., Griffini, S. et al. Eculizumab treatment in atypical hemolytic uremic syndrome: correlation between functional complement tests and drug levels. J Nephrol 35, 1205–1211 (2022). https://doi.org/10.1007/s40620-021-01187-8

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  • DOI: https://doi.org/10.1007/s40620-021-01187-8

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