Abstract: FR-PO1049
Suboptimal Dosing of Initial Eculizumab Therapy in aHUS?
Session Information
- Glomerular Diseases: Immunology and Inflammation - II
October 26, 2018 | Location: Exhibit Hall, San Diego Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1202 Glomerular Diseases: Immunology and Inflammation
Authors
- Duineveld, Caroline, Radboudumc, Nijmegen, Netherlands
- Wijnsma, Kioa L., Amalia Children's Hospital, Nijmegen, Netherlands
- Volokhina, Elena, Radboudumc, Nijmegen, Netherlands
- Van De Kar, Nicole, Amalia Children's Hospital, Nijmegen, Netherlands
- Wetzels, Jack F., Radboudumc, Nijmegen, Netherlands
Background
Atypical hemolytic uremic syndrome (aHUS) is caused by dysregulation of the alternative complement pathway. With the introduction of the complement inhibitor eculizumab the prognosis of aHUS patients has significantly improved. Initiation of eculizumab immediately at disease onset is advised to prevent persistent kidney injury. For complete blockade of the terminal complement pathway eculizumab trough levels of 50-100 µg/ml are recommended. However, recent data suggested that the advised treatment protocol may be insufficient: low eculizumab levels in the induction phase were followed by eculizumab levels exceeding the recommended trough levels in the maintenance phase. (Volokhina, 2017).
Methods
We have extended previous observations and evaluated all adult aHUS patients who were treated with eculizumab in our center from 2013 to 2018.
Results
Eculizumab was used as induction therapy 23 times in 19 adult aHUS patients. Eculizumab trough levels after the first dose were measured in 12 patients. Five patients did not maintain eculizumab levels of >50 µg/ml after the first dose.This was paralleled by incomplete complement blockade. After the second infusion target levels were attained in all patients. No differences in gender, body-weight, CRP, creatinine-protein ratio and the presence of edema at presentation were found between the patients who did and did not reach target level. Eculizumab levels after the second dose increased far above target range and resulted in near complete blockade of the classical complement pathway (measured with Wieslab® Euro Diagnostica complement system screen) in all patients (reference value 69-129%, complete deficiency <1%) (Figure).
Conclusion
After the first dose of eculizumab trough levels were not reached in 41% of the patients. Subsequent eculizumab levels exceed the recommendation. Our results suggest that the current induction protocol is insufficient: the first dose should be increased or the interval shortened, later doses may be reduced.
Funding
- Commercial Support –