PB0688 - Effect of PK Assessment on clinical outcomes for patients with moderate to severe Hemophilia A

Monday, July 11, 2022

6:30 PM – 7:30 PM

Location: Exhibition

Presentation Format: In-Person

Presenting Author(s)

Guy Young, MD

Director, Hemostasis and Thrombosis Center
Children's Hospital Los Angeles
Los Angeles, California, United States

Co-Author(s)

MC

Michael Callaghan

Physician
Children’s Hospital of Michigan, Detroit, MI, USA
Detroit, Michigan, United States
VB

Vinod Balasa

Division Chief and Medical Director
Valley Children's Healthcare, Madera, CA, USA
Madera, California, United States
AS

Amit Soni

Medical Director
Center for Inherited Blood Disorders, Orange, CA, USA
Orange, California, United States
SA

SANJAY AHUJA

Director - Hemophilia Program
University Hospitals Health System, Cleveland, OH
Cleveland, Ohio, United States
JR

Jonathan C. Roberts

Associate Medical Director and Associate Research Director
Bleeding and Clotting Disorders Institute, Peoria, IL, USA
Peoria, Illinois, United States
MS

Mindy L. Simpson

Pediatric Hematologist-Oncologist
Rush University medical Center
chicago, Illinois, United States
AF

Andrew Frick

Analyst
Trio Health Inc., Louisville, CO, USA
Louisville, Colorado, United States
Ali G. Mokdad, MD, PhD, MBA

Medical Director
Takeda
Sudbury, Massachusetts, United States
SX

Shan Xing

Director, US Medical New Product Planning
Takeda Development Center Americas, Inc., Cambridge, MA
Cambridge, Massachusetts, United States
JC

Jorge Caicedo

Senior Medical Director Hematology, US Medical
Takeda Development Center Americas, Inc., Cambridge, MA
Cambridge, Massachusetts, United States

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.