A risk-based scoring approach to individualize prophylaxis in patients with Hemophilia A: Results from the predict study

Abstract

Abstract To date, there is no consensus on what constitutes optimal prophylaxis in hemophilia A. In the absence of pharmacokinetic data, FVIII-based prophylactic regimens are often determined based on local clinical practice. Healthcare professionals (HCPs) often rely on patient characteristics, bleeding history and reported clinical information. The PREDICT study assessed the predictive value of a baseline clinical risk score, based on participant's phenotypic and biologic variables, to guide selection of the most appropriate prophylaxis regimen for achieving a favorable outcome when transitioning from a standard half-life (SHL) clotting factor concentrate to damoctocog alfa pegol. Twenty-one previously treated participants, ≥12 years of age with congenital hemophilia A and receiving SHL prophylaxis for ≥6 consecutive months in the year prior to screening, were enrolled. At baseline, each participant was assigned a total risk score (low, medium and high risk) based on five individually weighted variables: pre-study bleeding phenotype, prior treatment frequency, number of active target joints, von Willebrand Factor antigen levels, and physical activity. All participants initiated a 2x/week regimen with damoctocog alfa pegol for 4 weeks. Thereafter, regimen was modified according to their risk category: 2x/week for high-risk participants, Q5D for those with a medium risk score, throughout the 6-month study duration; and for low-risk participants, Q5D for 4 weeks was followed by a switch to a less frequent regimen (e.g. Q7D). A favorable outcome was defined when a participant remained on the score-assigned regimen with at least one of the following intra-individual improvements: (1) reduced annualized bleed rate (ABR) and decreased frequency of administration; (2) reduced ABR with similar frequency of administration, or (3) decreased frequency of administration with stable ABR. Data from 17/21 patients, with ≥4 months of bleed data, were included in the modified Intent to Treat analysis. When treated and untreated bleeds were considered, 12/17 (71%) participants achieved a favorable outcome. All 12 participants demonstrated improved ABR (defined as a reduction from pre-study ABR of ≥1); and 11/12 reduced their infusion frequency (≥2 fewer infusions per month). One participant maintained their 2x/week prophylaxis regimen with an improved ABR. When considering only treated bleeds, 13/17 (77%) participants achieved a favorable outcome. Across all 17 participants, the overall mean (SD) reduction in ABR was 8.0 (15.2). In the high-risk group, which maintained a 2x/week regimen throughout the study, the mean (SD) reduction was 16.2 (22.2). Regarding administration frequency, 19/21 participants who completed the full study period had a mean (SD) reduction of 6.9 (4.8) infusions/month. High-risk participants experienced an even greater reduction, averaging 8.5 (7.0) fewer infusions/month. At baseline, participants had a total of 25 target joints (per ISTH criteria); by study end, 96% of these had resolved. The PREDICT scoring system helped to guide individualized prophylaxis regimens with damoctocog alfa pegol, leading to favorable outcomes in 77% and 71% of participants, based on treated and total ABRs, respectively. Although limited by a small sample size, these findings provide early evidence that a risk-based scoring approach, incorporating patients' clinical and intrinsic characteristics, may support HCPs and patients globally as a valuable clinical guide in personalizing their prophylaxis regimen when transitioning from an SHL to an extended-half-life (EHL)-based regimen, like damoctocog alfa pegol.