Eculizumab Dosing Regimen in Atypical HUS: Possibilities for Individualized Treatment

Clin Pharmacol Ther. 2017 Oct;102(4):671-678. doi: 10.1002/cpt.686. Epub 2017 May 26.

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.

MeSH terms

  • Adult
  • Antibodies, Monoclonal, Humanized / administration & dosage*
  • Antibodies, Monoclonal, Humanized / pharmacokinetics
  • Atypical Hemolytic Uremic Syndrome / drug therapy*
  • Child
  • Child, Preschool
  • Complement Inactivating Agents / administration & dosage*
  • Complement Inactivating Agents / pharmacokinetics
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Female
  • Humans
  • Infant
  • Male
  • Middle Aged
  • Precision Medicine
  • Time Factors
  • Young Adult

Substances

  • Antibodies, Monoclonal, Humanized
  • Complement Inactivating Agents
  • eculizumab