Background & aims: Untreated atypical haemolytic syndrome (aHUS) leads to ESRD and may recur after renal transplantation. Eculizumab (Ecu), a humanized antibody inhibiting terminal C5 complement, is an expensive drug ($400,000,-/yr/pat) approved for treatment of aHUS and prevention of recurrence of aHUS posttransplant. At a serum level of Ecu > 50 ug/mL C5 complement is totally blocked¹ and this is reflected in a suppressed functional complement assay (CH50<10%, AP50<10%)².

We present a renal transplant patient treated by Eculizumab in whom Ecu dose could safely be reduced by monitoring Ecu pre-dose levels and functional complement assays.

Methods: Our patient had aHUS postpartum (Factor H mutation) and received a kidney transplantation 3 years later. Ecu was started for prevention of recurrence at the recommended dosing schedule (maintenance dose 1200mg q14days). After 6 months, the patient repeatedly experienced during and shortly after the infusion of Ecu 1200mg complaints of nausea, headache, and upper legs pain. To monitor the possibility and safety of dose reduction, pre-dose Ecu level, CH50/AP50 were measured. Dose-adjustments were made, guided by pre-dose Ecu level, CH50/AP50<10%. Adjustments were checked in steady state after at least 4 dose intervals.

Results: At 1200mg q14days, Ecu pre-dose level was >250 ug/mL with suppressed CH50 (1%) and AP50 (2%) . Dose reduction by 25% (to 900mg q14days) resulted in disappearance of her complaints with still 'elevated' pre-dose level and suppressed CH50 and AP50. Further dose reduction was performed by increasing dosing interval. Ecu 900mg q21days still resulted in a “high pre-dose level+ (± 180 ug/ml). At an Ecu dose of 900mg q28days, the pre-dose level was 62 mg/ml, with still suppressed CH50 (1%)/AP50 (3%) without any clinical or laboratory sign of aHUS activity. This 63.5% Ecu dose reduction (1200mg q14days to 900mg q28days) results for this patient into a saving of $250,000.- pro year on Ecu medication costs!

Conclusion: 1. Ecu has dose-related reversible side-effects. 2. Dose reduction improves patients QoL (no side-effects, larger dosing interval). 3. Dose reduction >60% is possible under monitoring of Ecu pre-dose level and safety/efficacy parameters reducing costs by $250,000.- pro year.

1. Legendre CM, et al. N Engl J Med 2013; 368:2169

2. Peffault de Latour R, et al. Blood. 2015 Jan 29;125(5):775.

CITATION INFORMATION: Gelens M, Havenith T, Damoiseaux J, Christiaans M. Eculizumab Dose Reduction Is Safe by Monitoring Eculizumab Pre-Dose Level and Functional Complement Assays. Am J Transplant. 2017;17 (suppl 3).

« Back to 2017 American Transplant Congress