Sensitive, reliable and easy-performed laboratory monitoring of eculizumab therapy in atypical hemolytic uremic syndrome
Volokhina, Elena B.; van de Kar, Nicole C.A.J.; Bergseth, Grethe; van der Velden, Thea J.A.M.; Westra, Dineke; Wetzels, Jack F.M.; van den Heuvel, Lambertus P.; Mollnes, Tom Eirik
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 C5were inversely correlated
to the complement activity (p=0.01).Moreover, titrating serumfromeculizumab-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.