The principles of PK-tailored prophylaxis

Summary

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 PKtailored 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.

Zusammenfassung

Prophylaxe mit Faktor VIII gilt als Therapie der Wahl für Patienten mit schwerer Hämophilie A, während das optimale Behandlungsregime weiterhin diskutiert wird. Vor kurzem wurde die Wirksamkeit und Sicherheit einer pharmakokinetisch (PK) gesteuerten Prophylaxe mit rFVIII (ADVATE) gezeigt mit dem Ziel den Faktor-VIII-Spiegel zu jeder Zeit über 1% zu halten (19). Die jährliche Blutungsrate konnte im Vergleich zur bedarfsgesteuerten Dosierung signifikant gesenkt werden (p < 0,0001), was mit einer Verbesserung der Lebensqualität verbunden war (SF-36v1 Schmerz-Score; p = 0,0007). Damit bietet die PK-gesteuerte Prophylaxe mit ADVATE eine wertvolle Alternative zur Standardprophylaxe. Offene Fragen, die für den Einsatz der PKgesteuerten Prophylaxe erwogen werden müssen, sind: Welcher Faktor-VIII-Spiegel darf zur Verhinderung von Blutungen nicht unterschritten werden? Haben Patienten mit Zielgelenken einen höheren Faktor-VIII-Spiegel Bedarf? Gibt es benutzerfreundliche Applikationen zur Berechnung einer individualisierten PK-gesteuerten Prophylaxe-Dosierung mit reduziertem Probenaufwand?

Der aktuelle Wissensstand sowie Erwägungen zur PK-gerichteten Prophylaxe werden im Folgenden diskutiert.

Keywords

Haemophilia A - PK tailored prophylaxis - annual bleed rate - ABR - individualized treatment - FVIII trough level - target joint

Schlüsselwörter

Hämophilie A - PK-gesteuerte Prophylaxe - Blutungsrate - individualisierte Behandlung - FVIII Plasmaspiegel - Zielgelenk

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