title: The principles of PK-tailored prophylaxis.
abstract: While prophylaxis with factor VIII (FVIII) is considered the first choice therapy for patients with severe haemophilia A the optimal prophylaxis regimen is still under scientific debate. A recent study demonstrated efficacy and safety of a PK-tailored prophylaxis regimen with rFVIII (ADVATE) aimed to maintain FVIII trough levels of ≥1% (19). The annual bleed rate (ABR) could be significantly reduced compared to the previous on-demand treatment period (p < 0.0001) and bodily pain, a health-related quality of life dimension of the SF-36v1 questionnaire also significantly improved (p = 0.0007). Thus PK-tailored prophylaxis with ADVATE might offer a valid alternative to standard prophylaxis. Open issues to be considered for implementation of PK-tailored prophylaxis are: What FVIII trough level is needed to prevent any bleed? Do patients with target joints need higher FVIII trough levels to stay bleed-free? Are there user-friendly tools available to calculate individualized PK-driven prophylaxis doses and frequency without the need for a full 9-sample PK curve? Current knowledge on these aspects as well as some considerations about the future of PK-tailored prophylaxis is discussed.
authors.affiliation: Prof. Dr. med. Armin J. Reininger, Baxter Innovations GmbH, Industriestr. 67, 1220 Vienna, Austria, Tel. +43/1/201 00-247 34 94 Fax +43/1/201 00-530, E-mail: armin_reininger@baxter.com.
authors.forename: A J
authors.initials: AJ
authors.lastname: Reininger
authors.forename: H E
authors.initials: HE
authors.lastname: Chehadeh
mesh_terms: D015415:Biomarkers / Q000097:blood; D004305:Dose-Response Relationship, Drug; D016903:Drug Monitoring / Q000379:methods*; D019317:Evidence-Based Medicine; D005169:Factor VIII / Q000008:administration & dosage* / Q000378:metabolism*; D006467:Hemophilia A / Q000097:blood* / Q000150:complications / Q000517:prevention & control*; D006470:Hemorrhage / Q000097:blood* / Q000209:etiology / Q000517:prevention & control*; D006801:Humans; D057285:Precision Medicine / Q000379:methods; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D011994:Recombinant Proteins; D005169:Factor VIII
keywords: ABR; FVIII trough level; Haemophilia A; PK tailored prophylaxis; annual bleed rate; individualized treatment; target joint