Stones from Other Mountains | Experience Sharing of the Latest Approved PK Software (1): Spanish Experience

Because there are individual differences in the pharmacokinetic (PK) characteristics, bleeding phenotypes, exercise patterns, and life goals of different patients with hemophilia1, different patients need to achieve different levels of factors.
Traditional standard dose preventive treatment (25-40IU/kg, 3 times a week) There are certain limitations1, and individualized preventive treatment plans need to be developed.

Among the many individualized preventive treatment plans, PK-guided individualized preventive treatment is the most effective plan for successful preventive treatment2.

Through the Bayesian algorithm, the PK detection sampling is reduced from at least 11 points in the past to 2-3 sampling points now2.

Recently, a web-based medical application-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 National Medical Products Administration (NMPA) Approved, applicable to hemophilia A patients 16 years and older (45kg and above) receiving rAHF-PFM treatment.
Estimate individual PK parameters based on their coagulation factor VIII laboratory data and personal information, and calculate the preventive treatment dose based on this parameter, For use by healthcare professionals (HCP) 3.

In order to better explore and summarize the clinical practice experience of PK software, in this issue, we will share the usage from Spain.

PK software clinical use background 4PK-guided individualized preventive treatment limitations: traditional PK parameter detection requires at least 6 time points (children) or 10 time points (adults) to collect blood samples, and the waiting time is long, usually for adults It brings troubles to children and their caregivers.
Therefore, although HCP prefers PK-guided individualized preventive treatment, the complexity of traditional PK testing makes PK-guided individualized preventive treatment unable to be widely and practically applied.PK software came into being: Based on the above situation, PK tools/software came into being, and only need at least 2 time points (the first one is between 3-4 hours ± 30 minutes after the infusion, and the second one is 24 hours after the infusion.
-32 hours ± 1 hour) to detect PK parameters.

Therefore, Mingot-Castellano ME and others used PK software in clinical practice for patients with severe hemophilia A in three hemophilia centers in Spain, and adjusted the preventive treatment according to the estimated PK parameters, individual joint state and physical activity.
The treatment outcome and factor dosage after the protocol were evaluated.

PK software clinical use method 4 A prospective and observational study involving 36 patients with severe hemophilia A who received rAHF-PFM preventive treatment from three hemophilia centers in Spain.
The specific study design is shown in Figure 1: Figure 1 Study design PK software clinical use Outcome 4 Bleeding was significantly reduced: Compared with the PK software-assisted, after the PK software-assisted, the bleeding of patients was reduced after the rAHF-PFM individualized preventive treatment (average ABR=2.
2 vs.
1.
5; P=0.
018, Average AJBR=1.
3 vs.
0.
7; P=0.
012).

The bleeding situation before and after PK software assistance is shown in Figure 2: Figure 2 Individualized rAHF-PFM prevention and treatment bleeding outcome changes after PK software assistance There is no significant difference in total factor dosage: compared with the preventive treatment factor dosage before PK software assistance After the PK software assisted, the FVIII dosage of most patients changed.
Among them, the annual factor dosage of 18 patients decreased, and the annual factor dosage of 14 patients increased.
There was no significant difference in the total annual factor dosage (199466±103670 vs.
198784±110387) IU/year).

Spanish PK software use experience sharing 4PK software can optimize the utilization of medical resources: According to Spanish experience, PK-guided individualized preventive treatment assisted by PK tools can improve clinical outcomes and optimize factor dosages.

Individualized preventive treatment under the guidance of PK, patients who may have been over-treated in the past can appropriately reduce the dosage of factors, and patients who are under-treated can appropriately increase the dosage of factors.

When the overall factor dosage is almost unchanged, the bleeding of patients is reduced, and the application of medical resources is more reasonable.

The clinical use of PK software is convenient and quick: 29 of the 36 patients (81%) only need 2 time points to sample to estimate the PK parameters, which reduces the number of sampling time points for the daily life and work of patients and medical staff Impact.

For patients who need more than 2 time points to sample, it may be because one of the two samples is closer to the extreme value of the population PK parameter simulated in the software, which affects the accuracy of the results, so combined with the software's operating manual and experts It is recommended that a sampling plan with more than 2 points is adopted.

Summary Spanish experience shows that individualized preventive treatment aided by PK software can improve bleeding without increasing the dosage of factors, and is effective in both children and adults with severe hemophilia A.

In addition, PK software only needs 2 time points to sample and estimate PK parameters, which brings more convenience to patients and medical staff in routine clinical practice.

References: 1.
Valentino LA,et al.
Haemophilia.
2009;15(Suppl 2):5-182.
Álvarez-Román MT,et al.
Haemophilia 2017 Jan;23(1)3.
Recombinant human coagulation factor VIII for injection Instructions for use of dose calculation software.
Revised 3.
04 in December 2020.
Mingot-Castellano ME,et al.
Haemophilia 2018 Sep;24(5):e338-e343VV-MEDMAT-43591 Learn about the latest developments in the field of related diseases.

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