[Translated article] Pharmacokinetics of eculizumab in adult and pediatric patients with atypical hemolytic uremic syndrome and C3 glomerulopathy.

Publisher: Elsevier España Country of Publication: Spain NLM ID: 9440679 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2171-8695 (Electronic) Linking ISSN: 11306343 NLM ISO Abbreviation: Farm Hosp Subsets: MEDLINE

Publication: 2023- : Madrid : Elsevier España
Original Publication: Madrid : Editorial Garsi,

Atypical Hemolytic Uremic Syndrome*/drug therapy; Adult ; Humans ; Child ; Middle Aged ; Antibodies, Monoclonal, Humanized/therapeutic use ; Spain

Objective: The objective of the study was to analyze and describe the concentrations of eculizumab and the complement blockade in patients with atypical hemolytic uremic syndrome (aHUS) and C3 glomerulopathy, and to define a therapeutic margin where there is a high probability of achieving therapeutic efficacy.
Methods: Observational, ambispective, and multicenter study that included adult and pediatric patients diagnosed with aHUS and C3 glomerulopathy from September 2020 to October 2022 in 5 hospitals in Spain. Eculizumab was administered at the doses recommended by the data sheet according to the European Medicines Agency (EMA). Pre- and post-dose concentrations of eculizumab were determined, as well as blockade of the classical complement pathway (CH50). Sociodemographic and clinical data were collected, and pharmacokinetic parameters were calculated. To establish the cut-off point for eculizumab concentrations that predicted complement blockade, Receiver Operating Characteristic (ROC) curve analysis was performed. Lastly, the Kruskal-Wallis test was used to contrast the differences in different parameters according to eculizumab concentrations.
Results: Twenty-five patients were included, 19 adults (76.0%) and 6 pediatrics (24.0%), with median ages of 43.4 (interquartile range (IQR) 35.7-48.8) and 10.1 (IQR 9.6-11.3) years, respectively. Of these, 22 (88.0%) patients were diagnosed with aHUS and 3 (12.0%) with C3 glomerulopathy. A total of 111 eculizumab concentrations were determined. Mean pre- and post-dose concentration values detected during the maintenance phase were 243.8 (SD 240.6) μg/mL and 747.4 (standard deviation (SD) 444.3) μg/mL, respectively. Increased complement blockade was observed at higher pre-dose concentrations (P = .002) and decreased serum creatinine at both higher pre- and post-dose concentrations (P = .001 and P = .017, respectively). Using ROC curves, it was determined that a pre-dose concentration >149.0 μg/mL was optimal to achieve complement blockade, with an AUC of 0.87 (0.78-0.95). Finally, high inter-individual (48.9% variation coefficient (CV)) with low intra-individual variabilities (11.9% CV) in eculizumab clearance were observed.
Conclusions: The present study reports supratherapeutic concentrations of eculizumab in patients with aHUS, and defines higher concentrations than those described in the data sheet to achieve blockade, thus encouraging the personalization of treatment with eculizumab.
Competing Interests: Conflict of interest None declared.
(Copyright © 2023 Sociedad Española de Farmacia Hospitalaria (S.E.F.H). Publicado por Elsevier España, S.L.U. All rights reserved.)

Keywords: Anticuerpos monoclonales humanizados; Drug monitoring; Ecolizumab; Eculizumab; Farmacocinética; Farmacodinamia; Hemolytic uremic syndrome; Humanized monoclonal antibodies; Monitorización farmacocinética; Pharmacodynamics; Pharmacokinetics; Síndrome hemolítico urémico

A3ULP0F556 (eculizumab)
0 (Antibodies, Monoclonal, Humanized)

Date Created: 20231206 Date Completed: 20240109 Latest Revision: 20240201

20240202

10.1016/j.farma.2023.09.009

38057242