Clinical Utility and Potential Cost Savings of Pharmacologic Monitoring of Eculizumab for Complement-Mediated Thrombotic Microangiopathy.

Abstract

One of the treatment options for complement-mediated thrombotic microangiopathy (CM-TMA), also known as atypical hemolytic uremic syndrome, is the administration of the C5 complement inhibitor eculizumab. In vivo studies have reported a complete complement blockade with eculizumab serum concentrations above 50 μg/mL in the case of atypical hemolytic uremic syndrome. The eculizumab trough levels and C5 functional activity were monitored in patients with CM-TMA being treated with eculizumab. For those with eculizumab trough concentrations of more than 100 μg/mL, the frequency of eculizumab 1200-mg doses was decreased. In this article, we describe the pharmacologic monitoring data with the use of C5 functional activity and mass spectrometric assessments of eculizumab to allow for a tailored eculizumab schedule for 10 patients with CM-TMA. In 9 out of 10 (90%) patients with a standard administration schedule, eculizumab trough concentrations were more than 100 μg/mL. At the time of the last eculizumab follow-up (median, 250 days; range, 85-898 days), the interval between eculizumab infusions was extended to every 3-6 weeks for 8 patients; no disease relapse was found with the modified dosing interval. Altering the administration of maintenance eculizumab from every 2-3 weeks to 3-6 weeks yields a savings of $78,185 per patient for a 6-month eculizumab treatment course. Although larger standardized cohorts are necessary to confirm these findings, our data suggest that monitoring eculizumab levels in conjunction with C5 assessment allows for safe modification of eculizumab dosing and results in considerable cost savings.