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Evaluation of FVIII Low-dose Prophylaxis using Pharmacometric Models: A Simulation Study
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences. (Pharmacometrics Group)
2017 (English)Independent thesis Advanced level (degree of Master (One Year)), 20 credits / 30 HE creditsStudent thesis
Abstract [en]

Introduction: Patients with severe hemophilia A have missing or defective clotting factor VIII (FVIII). Untreated, patients may bleed spontaneously into joints causing arthropathy and disability. The optimal treatment modality for hemophilia A is lifelong prophylaxis which is expensive and may not be implementable everywhere where FVIII availability is limited. A cheaper alternative to prophylaxis is low-dose prophylaxis (LDP). The efficacy of LDP compared to conventional prophylaxis can be evaluated using simulations from a pharmacometric model.

Aim: i) Ascertain whether the use of LDP is motivated where conventional prophylaxis is not implementable. ii) To investigate whether dose tailoring can decrease costs and improve the distribution of available FVIII based on individual patient pharmacokinetic (PK) parameters.

Methods: A population of 2000 hemophilia A patients were simulated given a previously developed 2-compartment population PK model in NONMEM. The simulated treatment regimens in the patients included very LDP (VLDP), LDP and conventional prophylaxis twice and thrice weekly. In addition, PK-based dose tailoring was evaluated to determine FVIII savings.

Results: A 5% increase in median probability of annual bleed gave a 75% decrease in costs. Dose tailoring proved cost-saving, however, depending on the activity goal, only a few additional patients would benefit.

Conclusion: According to the results, LDP and VLDP decrease costs at a small increase in risk. However, the results should be interpreted with caution due to the limitations regarding the PK model as well as the outcome model. Further, these results would need to be adapted to the needs of every clinic individually, which may vary greatly depending on the availability of FVIII. 

Place, publisher, year, edition, pages
2017. , 38 p.
Keyword [en]
pharmacometrics, simulation, hemophilia, fviii, low-dose prophylaxis, prophylaxis, population pharmacokinetics
National Category
Pharmaceutical Sciences
Identifiers
URN: urn:nbn:se:uu:diva-325906OAI: oai:DiVA.org:uu-325906DiVA: diva2:1117416
Subject / course
Pharmacokinetics
Educational program
Master of Science Programme in Pharmacy
Supervisors
Examiners
Available from: 2017-06-29 Created: 2017-06-28 Last updated: 2017-06-29Bibliographically approved

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CiteExportLink to record
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Citation style
  • apa
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