Background: Complement-mediated thrombotic microangiopathy (aHUS) is treated with the C5-complement inhibitor eculizumab (ECU). For adults, the standard ECU administration schedule is four-900mg weekly infusions followed by 1200mg every two weeks. In-vivo studies have demonstrated complete complement blockade with ECU serum concentrations above 50 µg/mL for aHUS. We have been monitoring ECU trough levels (ECUT) and C5 functional activity (C5FA) for patients with aHUS. For those with ECUT > 100 µg/mL, frequency of ECU 1200mg doses has been decreased.

Aims: Review ECUT obtained according to institution ECU administration practices and perform cost-savings analysis for personalized ECU administration.

Methods: Laboratory database was queried for patients with ECUT and C5FA since the introduction of these assays in 2018. Inclusion criteria included patients with a clinical diagnosis of aHUS receiving medical care at Mayo Clinic. Only patients with clinically confirmed ECUT were included.

Results: 9 patients met inclusion criteria and ECUT ranged from 46- 518 µg/mL(Table 1). There was no uniform time when ECUT were obtained in relation to ECU initiation due to variability of patient referral to our institution. ECUT was > 100 µg/mL in 8/9 (89%) patients with the standard administration schedule. At the time of last ECU follow-up (147 (64-674) days, n=6), ECU infusions were prolonged to every three, four, and five weeks for three, one, and two patients, respectively. Nobody experienced a disease relapse with the modified dosing interval. Altering administration from every two to three weeks yields a savings of $110,244/patient every six months (Table 2).

Conclusions: In this study, the standard ECU administration schedule was not necessary for most patients. Use of ECUT over C5FA alone, allows for a more nuanced tailoring approach. Although larger standardized cohorts are necessary to confirm these findings, our preliminary data suggests that personalized dosing of eculizumab using ECUT and C5FA is safe and provides significant cost-saving.

[Table 1: Demographics and Eculizumab Trough Levels]

[Table 2: Cost-Savings Analysis of Tailored Eculizumab Administration]

« Back to ISTH 2020 Congress

ISTH Congress Abstracts - https://abstracts.isth.org/abstract/personalized-dosing-of-eculizumab-using-c5-functional-activity-and-eculizumab-level-in-complement-mediated-thrombotic-microangiopathy-a-safe-and-cost-saving-approach/