ESPN 50th Annual Meeting

ESPN 2017


 
Eculizumab dosing regimen in atypical HUS: possibilities for individualized treatment
ELENA VOLOKHINA 1 KIOA WIJNSMA 1 RENATE VAN DER MOLEN 1 NEL ROELEVELD 1 THEA VAN DER VELDEN 1 JOOP GOERTZ 1 FRED SWEEP 1 ROGER BRUGGEMANN 1 JACK WETZELS 1 NICOLE VAN DE KAR 1 LAMBERTUS VAN DEN HEUVEL 1

1- RADBOUDUMC
 
Introduction:

Recent studies indicate that eculizumab is often given in excess to aHUS patients. Individualization of treatment is thus highly requested, however, data on pharmacokinetics and pharmacodynamics of eculizumab remain limited.

Material and methods:

Serum eculizumab and complement activity (CH50) were measured by in-house ELISA-based methods. In total, 209 samples were taken from 11 patients before the eculizumab infusion in the induction (weekly), maintenance (2-weekly) and tapering (every 3, 4 and 5 weeks) phases of therapy. Statistical analysis was performed using linear mixed models.

Results:

The trough eculizumab levels increased with each additional dose during the induction phase (depending on body weight). During maintenance, high eculizumab concentrations of up to 772 µg/mL were observed. The levels decreased with each following dose during tapering (3- and 4-week intervals), however three patients maintained target eculizumab levels over long time periods (30-48 weeks). At intervals of 6-8 weeks target eculizumab levels were no longer attained. Serum samples with eculizumab concentrations ≥50 µg/mL showed full complement blockade.

Conclusions:

Our data provide essential insight for optimization of eculizumab dosing schemes and lessening of therapy burden for the patients and cost of the treatment.