Effect of PK Assessment on clinical outcomes for patients with moderate to severe Hemophilia A

G. Young¹, M. Callaghan², V. Balasa³, A. Soni⁴, S. Ahuja⁵, J. Roberts⁶, M. Simpson⁷, A. Frick⁸, A. Mokdad⁹, S. Xing¹⁰, J. Caicedo¹⁰

¹Children’s Hospital Los Angeles, University of Southern California Keck School of Medicine, Los Angeles, CA, USA, Los Angeles, California, United States, ²Children’s Hospital of Michigan, Detroit, MI, USA, Detroit, Michigan, United States, ³Valley Children's Healthcare, Madera, CA, USA, Madera, California, United States, ⁴Center for Inherited Blood Disorders, Orange, CA, USA, Orange, California, United States, ⁵Rainbow Babies and Children's Hospital, Cleveland, OH, USA, Cleveland, Ohio, United States, ⁶Bleeding and Clotting Disorders Institute, Peoria, IL, USA, Peoria, Illinois, United States, ⁷Rush University Medical Center, Chicago, IL, USA, Chicago, Illinois, United States, ⁸Trio Health Inc., Louisville, CO, USA, Louisville, Colorado, United States, ⁹Takeda, Sudbury, Massachusetts, United States, ¹⁰Takeda Development Center Americas, Inc., Cambridge, MA, Cambridge, Massachusetts, United States

Abstract Number: PB0688

Meeting: ISTH 2022 Congress

Theme: Hemophilia and Rare Bleeding Disorders » Hemophilia - Clinical

Background: Individualized pharmacokinetic (PK)-guided prophylaxis has been shown to improve outcomes in patients with hemophilia A (PWHA) in clinical trials; however, PK-guided testing in real-world settings is poorly understood.

Aims: This retrospective chart review examined clinical outcomes for patients before and after PK testing in US hemophilia treatment centers (HTC).

Methods: This study included 132 male PWHA from 7 HTCs with moderate or severe disease, ≥3 months prior FVIII prophylaxis and up to 12 months FVIII prophylaxis after PK-guided prescription change (index date), no inhibitors prior to index date, and no concurrent participation in clinical trials. Change in mean annualized bleed rate (ΔABR) and confidence intervals (CIs) were calculated using patient bleed logs.

Results: Of the 132 patients (age: median = 13, range: 2-43; severe disease: 93.2%), 58 (44%) remained on the same FVIII (non-switchers) and 74 (56%) switched FVIII therapy (switchers) after PK assessment. The majority (95%) of switchers had transitioned from a standard half-life (SHL) to extended half-life (EHL) product. ABR decreased for the entire cohort post-index [-0.97 (95% CI:-1.54,-0.42)], driven by a decrease in joint bleeds [-0.77 (-1.23,-0.34)]. Decrease in ABR was larger among non-switchers [-1.93 (-3.14, -0.78)], similarly driven by a decrease in joint bleeds [-1.43 (-2.45, -0.54)]. Although switchers did not have a significant decrease in ABR [-0.35 (-0.78, 0.06)], switchers had lower ABRs before PK-guided prophylaxis vs non-switchers (1.23 vs 3.85, respectively) and maintained lower ABRs after index date (0.88 vs 1.93).

Conclusion(s): Individualized pharmacokinetic-guided prophylaxis was associated with an overall reduction in ABR in both FVIII switchers and non-switchers, with results more pronounced among non-switchers. Dose adjustments based on PK testing could be a useful strategy for optimizing treatment for those remaining on same SHL or EHL therapy and maintaining proper trough levels in patients switching from SHL to EHL.

Table

Table 1: Patient Characteristics at Index Date

Table 2

Change in Annualized Bleed Rate -95% CI- in All Patients and Stratified by Switching Status

To cite this abstract in AMA style:

Young G, Callaghan M, Balasa V, Soni A, Ahuja S, Roberts J, Simpson M, Frick A, Mokdad A, Xing S, Caicedo J. Effect of PK Assessment on clinical outcomes for patients with moderate to severe Hemophilia A [abstract]. https://abstracts.isth.org/abstract/effect-of-pk-assessment-on-clinical-outcomes-for-patients-with-moderate-to-severe-hemophilia-a/. Accessed November 30, 2023.

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