title: Eculizumab Dosing Regimen in Atypical HUS: Possibilities for Individualized Treatment.
abstract: Recent studies indicate that eculizumab is often given in excess to atypical hemolytic uremic syndrome (aHUS) patients. Individualization of treatment is thus highly requested; however, data on the pharmacokinetics and pharmacodynamics of eculizumab remain limited. We analyzed 11 patients during induction (weekly), maintenance (2-weekly), and tapering (every 3-8 weeks) phases of treatment. 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 adequate complement blockade. Our data provide essential insight for optimization of eculizumab dosing schemes and lessening of therapy burden for the patients and cost of the treatment.
authors.affiliation: Department of Pediatric Nephrology, Amalia Children's Hospital, Radboud University Medical Center, Nijmegen, The Netherlands.|Department of Laboratory Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: E
authors.initials: E
authors.lastname: Volokhina
authors.affiliation: Department of Pediatric Nephrology, Amalia Children's Hospital, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: K
authors.initials: K
authors.lastname: Wijnsma
authors.affiliation: Department of Laboratory Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: R
authors.initials: R
authors.lastname: van der Molen
authors.affiliation: Department of Pediatric Nephrology, Amalia Children's Hospital, Radboud University Medical Center, Nijmegen, The Netherlands.|Department of Health Evidence, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: N
authors.initials: N
authors.lastname: Roeleveld
authors.affiliation: Department of Pediatric Nephrology, Amalia Children's Hospital, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: T
authors.initials: T
authors.lastname: van der Velden
authors.affiliation: Department of Laboratory Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: Goertz
authors.affiliation: Department of Laboratory Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: F
authors.initials: F
authors.lastname: Sweep
authors.affiliation: Department of Pharmacy, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: R J
authors.initials: RJ
authors.lastname: Brüggemann
authors.affiliation: Department of Nephrology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: Wetzels
authors.affiliation: Department of Pediatric Nephrology, Amalia Children's Hospital, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: N
authors.initials: N
authors.lastname: van de Kar
authors.affiliation: Department of Pediatric Nephrology, Amalia Children's Hospital, Radboud University Medical Center, Nijmegen, The Netherlands.|Department of Laboratory Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.|Department of Pediatrics, University Hospitals Leuven, Leuven, Belgium.
authors.forename: L
authors.initials: L
authors.lastname: van den Heuvel
mesh_terms: D000328:Adult; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage* / Q000493:pharmacokinetics; D065766:Atypical Hemolytic Uremic Syndrome / Q000188:drug therapy*; D002648:Child; D002675:Child, Preschool; D051056:Complement Inactivating Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D057285:Precision Medicine; D013997:Time Factors; D055815:Young Adult
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D051056:Complement Inactivating Agents; C481642:eculizumab