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Abstract: SA-PO458

CH50 Result Variability by Methodology in Eculizumab-Treated Patients with Atypical Hemolytic Uremic Syndrome

Session Information

  • Pediatric Nephrology - II
    October 27, 2018 | Location: Exhibit Hall, San Diego Convention Center
    Abstract Time: 10:00 AM - 12:00 PM

Category: Pediatric Nephrology

  • 1600 Pediatric Nephrology

Authors

  • Cody, Ellen, University of Colorado School of Medicine, Aurora, Colorado, United States
  • Frazer-Abel, Ashley, University of Colorado School of Medicine, Aurora, Colorado, United States
  • Dixon, Bradley P., University of Colorado School of Medicine, Aurora, Colorado, United States
Background

The advent of complement-targeted therapy for the treatment of atypical hemolytic uremic syndrome (aHUS) has led to an increasing use of pharmacodynamic monitoring in patients to ensure adequate complement blockade to suppress disease activity. Measurement of terminal pathway activity and functionality with plasma sC5b-9 and CH50, respectively, have gained wide acceptance as means to assess the adequacy of complement blockade in such patients. However, methodologies for the CH50 assay may vary widely among institutions, and some methodologies may be insufficiently sensitive to determine such adequacy of blockade.

Methods

In patients treated with eculizumab for aHUS and other forms of thrombotic microangiopathy, CH50 was clinically measured at regular intervals during the induction phase of treatment by a laboratory-developed standard hemolytic assay. We compared these results to results obtained by two additional methods, the Wieslab CP assay and an instrument-based liposomal assay for CH50. Adequate complement blockade was defined as a CH50 value less than 10% of the lower limit of normal for each assay.

Results


We identified that in a number of patients treated with eculizumab, breakthrough of complement blockade prior to the next scheduled dose of eculizumab was noted by an upward trend of CH50 results obtained by hemolytic methodology, whereas values obtained by both Wieslab CP and instrument-based methodologies suggested ongoing suppression and did not detect this breakthrough in blockade. Breakthrough of complement blockade in several instances influenced therapeutic decision making, in which supplemental doses were administered to ensure sufficiency of suppression of disease activity.

Conclusion

These findings suggest that the sensitivity of CH50 to detect small but clinically meaningful changes in complement suppression may differ by assay methodology, and that care must be taken in the interpretation of the results of these assays for pharmacodynamic monitoring of patients on eculizumab.