Sensitive, reliable and easy-performed laboratory monitoring of eculizumab therapy in atypical hemolytic uremic syndrome
AuthorVolokhina, 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
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.
Published version also available at http://dx.doi.org/10.1016/j.clim.2015.05.018