ArticleNephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association2023
Proposal for individualized dosing of eculizumab in atypical haemolytic uraemic syndrome: patient friendly and cost-effective.
Article in Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 1 of them a synthesis that pooled it.
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Who cites it
11 citing papers in PubMed, 1 synthesis or guideline pooled it, 14 citations in OpenAlex.
- Recommendations for diagnosis and treatment of Atypical Hemolytic Uremic Syndrome (aHUS): an expert consensus statement from the Rare Diseases Committee of the Brazilian Society of Nephrology (COMDORA-SBN).Jornal brasileiro de nefrologiaGuideline
- Exploring individualized crovalimab dosing in PNH through in silico modelling: Potential for improved convenience and cost efficiency.British journal of clinical pharmacology · 2026Article
- Biologics in Kidney Transplantation: Why and How Should We Personalize Their Dosage?BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2026Review
- Therapeutic advances in eculizumab for atypical hemolytic uremic syndrome: a narrative review.Frontiers in pharmacology · 2026Review
- Eculizumab-Induced Acute Heart Failure Decompensation in a Patient with Clinically Suspected Complement-Mediated Thrombotic Microangiopathy: A Case Report.Infection and drug resistance · 2026Article
- Model-Informed Precision Dosing of Eculizumab in Patients with Paroxysmal Nocturnal Hemoglobinuria.Clinical pharmacokinetics · 2025Observational
- Differential effects of C5 inhibition, C3 inhibition, and alternative pathway inhibition on bacterial killing in vitro.Blood advances · 2025Article
- Kidney Transplantation in Patients With aHUS: A Comparison of Eculizumab Prophylaxis Versus Rescue Therapy.Transplantation · 2025Article
- Prospective validation of initial eculizumab dosing in adults with atypical hemolytic uremic syndrome.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2025Article
- Outcomes from the International Society of Nephrology Hemolytic Uremic Syndromes International Forum.Kidney international · 2024Article
- Eculizumab Rescue Therapy in Patients With Recurrent Atypical Hemolytic Uremic Syndrome After Kidney Transplantation.Kidney international reports · 2023Article
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundEculizumab is a lifesaving yet expensive drug for atypical haemolytic uraemic syndrome (aHUS). Current guidelines advise a fixed-dosing schedule, which can be suboptimal and inflexible in the individual patient.
methodsWe evaluated the pharmacokinetics (PK) and pharmacodynamics (PD) [classical pathway (CP) activity levels] of eculizumab in 48 patients, consisting of 849 time-concentration data and 569 CP activity levels. PK-PD modelling was performed with non-linear mixed-effects modelling. The final model was used to develop improved dosing strategies.
resultsA PK model with parallel linear and non-linear elimination rates best described the data with the parameter estimates clearance 0.163 L/day, volume of distribution 6.42 L, maximal rate 29.6 mg/day and concentration for 50% of maximum rate 37.9 mg/L. The PK-PD relation between eculizumab concentration and CP activity was described using an inhibitory Emax model with the parameter estimates baseline 101%, maximal inhibitory effect 95.9%, concentration for 50% inhibition 22.0 mg/L and Hill coefficient 5.42. A weight-based loading dose, followed by PK-guided dosing was found to improve treatment. On day 7, we predict 99.95% of the patients to reach the efficacy target (CP activity <10%), compared with 94.75% with standard dosing. Comparable efficacy was predicted during the maintenance phase, while the dosing interval could be prolonged in ∼33% of the population by means of individualized dosing. With a fixed-dose 4-week dosing interval to allow for holidays, treatment costs will increase by 7.1% and we predict 91% of the patients will reach the efficacy target.
conclusionsA patient-friendly individualized dosing strategy of eculizumab has the potential to improve treatment response at reduced costs.
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