Sensitive, reliable and easy-performed laboratory monitoring of eculizumab therapy in atypical hemolytic uremic syndrome

Elena B Volokhina; Nicole C A J van de Kar; Grethe Bergseth; Thea J A M van der Velden; Dineke Westra; Jack F M Wetzels; Lambertus P van den Heuvel; Tom Eirik Mollnes

doi:10.1016/j.clim.2015.05.018

Sensitive, reliable and easy-performed laboratory monitoring of eculizumab therapy in atypical hemolytic uremic syndrome

Clin Immunol. 2015 Oct;160(2):237-43. doi: 10.1016/j.clim.2015.05.018. Epub 2015 Jun 23.

Authors

Elena B Volokhina¹, Nicole C A J van de Kar¹, Grethe Bergseth², Thea J A M van der Velden¹, Dineke Westra¹, Jack F M Wetzels³, Lambertus P van den Heuvel⁴, Tom Eirik Mollnes⁵

Affiliations

¹ Department of Pediatric Nephrology (774), Radboud University Medical Center, P. O. Box 9101, 6500 HB Nijmegen, The Netherlands.
² Research Laboratory, Nordland Hospital, P. O. Box 1480, 8092 Bodø, Norway.
³ Department of Nephrology (464), Radboud University Medical Center, P. O. Box 9101, 6500 HB, Nijmegen, The Netherlands.
⁴ Department of Pediatric Nephrology (774), Radboud University Medical Center, P. O. Box 9101, 6500 HB Nijmegen, The Netherlands; Department of Laboratory Medicine (774), Radboud University Medical Center, P. O. Box 9101, 6500 HB Nijmegen, The Netherlands; Department of Pediatrics, University Hospitals Leuven, Herestraat 49, 3000 Leuven, Belgium.
⁵ Research Laboratory, Nordland Hospital, P. O. Box 1480, 8092 Bodø, Norway; Faculty of Health Sciences, K.G. Jebsen TREC, University of Tromsø, P. O. Box 6050 Langnes, 9037 Tromsø, Norway; Centre of Molecular Inflammation Research, Norwegian University of Science and Technology, NO-7491 Trondheim, Norway; Department of Immunology, Oslo University Hospital, and K.G Jebsen IRC, University of Oslo, P.B. 4950 Nydalen, NO-0424 Oslo, Norway. Electronic address: t.e.mollnes@medisin.uio.no.

PMID: 26111482
DOI: 10.1016/j.clim.2015.05.018

Abstract

Complement C5 inhibitor eculizumab treatment in atypical hemolytic uremic syndrome is effective, but associated with high costs. Complement inhibition monitoring in these patients has not been standardized. In this study we evaluated novel functional assays for application in routine follow-up. We documented that the Wieslab® complement screen assay showed a sensitivity of 1-2% of C5 activity by adding purified C5 or normal human serum to a C5 deficient serum. All the patient samples obtained during the treatment course, were completely blocked for terminal complement pathway activity for up to four weeks after the eculizumab infusion. Levels of complexes between eculizumab and C5 were inversely correlated to the complement activity (p=0.01). Moreover, titrating serum from eculizumab-treated patients into normal serum revealed that eculizumab was present in excess up to four weeks after infusion. Thus, we demonstrate sensitive, reliable and easy-performed assays which can be used to design individual eculizumab dosage regimens.

Keywords: Complement; Eculizumab; Hemolytic uremic syndrome; Personalized therapy.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Adult
Antibodies, Monoclonal, Humanized / therapeutic use*
Atypical Hemolytic Uremic Syndrome / drug therapy*
Atypical Hemolytic Uremic Syndrome / immunology
Child
Child, Preschool
Complement Activation / immunology
Complement Inactivating Agents / therapeutic use*
Dose-Response Relationship, Drug
Drug Monitoring / instrumentation*
Drug Monitoring / methods
Female
Humans
Male
Reagent Kits, Diagnostic*
Reproducibility of Results
Young Adult

Substances

Antibodies, Monoclonal, Humanized
Complement Inactivating Agents
Reagent Kits, Diagnostic
eculizumab