Recently, the pharmacokinetic (PK)-guided hemophilia A management tool (recombinant human coagulation factor VIII dose calculation software for injection, hereinafter referred to as "PK software") has been approved by the State Drug Administration (NMPA) for hemophilia A patients aged 16 years and older (weighing 45 kg and above) receiving rAHF-PFM therapy.
The excitement is uninterrupted, and the knowledge is not stopped. In this issue, we bring you the British experience of PK software, and "add bricks and tiles" to the experience of PK software use, let's take a look!
UK Experience Sharing – Background on clinical use of the PK tool
Preventive therapy is the standard of care for patients with severe hemophilia A1. Due to differences in the bleeding phenotype of patients, maintaining only FVIII trough concentrations >1 IU/dL will still be at risk of bleeding under standard dose prophylaxis1. Therefore, individualized prophylaxis is required to adapt the patient's hemorrhagic phenotype and lifestyle1.
PK-guided individualized preventive therapy can reduce the risk of bleeding in patients with hemophilia, reduce the frequency and dose of coagulation factor infusion, increase the concentration of factor valley, and reduce medical costs, so that patients can expect to live an ideal life. However, the traditional detection and calculation of PK parameters is very cumbersome and the waiting time is long, and it cannot be widely used in practice2. The approval of PK software makes up for the lack of traditional PK detection.
UK Experience Sharing - PK Software Clinical Use Study Design 1
A prospective multicentre study of 59 patients from 16 centers, of whom 16 patients dropped out of the study and 8 patients did not undergo PK testing.
The patient's PK curve was modeled using PK software, and the FVIII trough concentration of the preventive treatment regimen (which changed in treatment) before and after the PK software-assisted was estimated. Patients were grouped according to trough concentrations and bleeding rates at the beginning, middle, and end of the study.
UK Experience Sharing – PK Software Clinical Use Outcome 1
PK software-assisted preventive treatment reduces bleeding
Compared with the pre-PK software- assisted, the proportion of patients with 0 bleeding increased from 36% to 50% after individualized prophylaxis treatment assisted by PK software, as shown in Figure 1.
Figure 1 Ratio of 0 bleeding patients before PK software aid vs PK software aid
At 12 months, the total median bleeding rate decreased (from 1 to 0.5, P=0.044) (Figure 2) with similar weekly median factor uses of 86 IU/kg and 82 IU/kg, respectively.
Figure 2 Bleeding before PK software assistance vs. PK software assistance
PK software-aided prophylactic treatment of patients with elevated FVIII trough concentrations
Among the patients who adjusted the prophylactic regimen with the assistance of PK software, 13 (81%) had higher trough concentrations (median >2 IU/dL) and a reduced bleeding rate (median bleeding rate from 2 to 1).
Of the patients who adjusted the preventive treatment regimen with the assistance of PK software, 15 (94%) had an increased frequency of treatment, and 5 patients received daily treatment for at least a specific period of time for a week.
With the aid of PK software, the proportion of patients with the optimal prophylactic regimen increased from 33% to 44% at 12 months (i.e., trough concentrations > 1, bleeding 0-1), the proportion of patients with trough concentrations <1 decreased from 34% to 23%, and the proportion of patients with trough concentrations >1 increased from 66% to 77%.
UK Experience Sharing – Patient Self-Reported PK Software Uses Outcome 1
Through the online Haemtrack system, patients self-documented treatment and bleeding, with 52/54 patients entering data at 6 months before trial enrollment and 12 months after trial start.
At the start of the study, 21 (40%) patient data met the Haemtrack system data entry criteria, and 40 (76%) and 35 (67%) patient data met the entry criteria in the middle and end of the study, respectively.
According to patient self-reported data, the amount of median factor remained unchanged, and the number of bleeding after preventive treatment with PK software was reduced (the median bleeding was from 4 to 2 at 6 months), as shown in Table 1:
Table 1 Patients who met the Criteria for Data Entry in the Haemtrack System in the trial were treated for prophylaxis and bleeding
brief summary
From the British experience, it can be seen that the assistance of PK software increases the concentration of FVIII trough and the proportion of patients with 0 bleeding. PK-guided preventive therapy can develop individualized preventive treatment regimens for patients. Group PK-guided preventive therapy is an important step in individualized therapy.
bibliography:
1. Saket Badle,et al. UKPK trial interim analysis: Use of Pharmacokinetic intervention to optimise Factor VIII prophylaxis in severe haemophilia A.WFH 2018.
2. https://www.advate.com/mypkfit.
Approval number: VV-MEDMAT-55300
Approval time: 10/22/2021
Expiry date: 10/22/2023
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