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The preventive treatment of hemophilia patients with fixed infusion mode does not achieve the optimal effect

Recently, the Chinese Hemophilia Collaborative Group, combined with relevant evidence-based medicine at home and abroad and the latest guidelines, officially issued the "Chinese Expert Consensus on Pharmacokinetics Guiding the Treatment of Hemophilia A", which is FⅧ in the clinical practice of hemophilia A in China.

Point 1: FⅧ Clinical significance and influencing factors of PK parameters

The PK designated amount of FⅧ is used to study the distribution, metabolism and elimination of exogenous FⅧ in the human body

Main PK parameters and clinical significance (Figure 1, Table 1)

Figure 1 PK parameters of FⅧ

Table 1 Clinical significance of PK parameters of FⅧ

Factors affecting FⅧ PK parameters

The influence of FⅧ:C detection: As the stability of FⅧ:C in plasma is easily affected by many factors, the collection, transportation, storage, inspection and other links of specimens can affect the experimental results.

The influence of individual differences: The PK parameters of FⅧ are affected by factors such as age, weight, blood type, von Willebrand factor (vWF) and inhibitors

Point 2: FⅧ PK evaluation model/software

Based on population (pop) PK model + Bayesian probability algorithm is currently recognized and effective individualized drug delivery method, which can predict individual PK parameters relatively accurately and reliably

In addition, domestic scholars have also proposed an improved one-room model method based on the classic PK model to obtain individual PK parameters

Table 2 Comparison of different PK analysis methods

Point 3: PK-guided individualized treatment of hemophilia A

• If the trough level reaches 1% , but there is still frequent bleeding: develop a targeted plan for a higher trough level
  
  Step2: Assist in determining the target trough level Step2: Assist in determining the target trough level Different patients, different bleeding phenotypes, different activity states, different joint conditions, the needs of trough levels are different: different patients, different bleeding phenotypes, different activity states, and different Under the condition of joints, the needs of the valley level are different:

  • Patients with target joints, the target valley level is higher than those without target joints;

  • The target valley level demand in the exercise state is higher than that in the no exercise state

    
    

• Patients with target joints, the target valley level is higher than those without target joints;

Patients with target joints, the target valley level is higher than those without target joints;

Patients with target joints, the target valley level is higher than those without target joints;

• The target valley level demand in the exercise state is higher than that in the no exercise state

  
  

The target valley level demand in the exercise state is higher than that in the no exercise state


The target valley level demand in the exercise state is higher than that in the no exercise state

Step3: Formulate and optimize the dosing plan Step3: Formulate and optimize the dosing plan

Comprehensive formulation of PK characteristics + treatment cost + patient life>+ acceptable treatment frequency: clinically, it is possible to combine the patient's individual PK characteristics, objective needs and different treatment goals to choose a preventive treatment plan that suits the patient's frequency and dosage of drugs as much as possible , in order to achieve The best cost-benefit ratio


PK PK characteristic features + + treatment costs treatment costs + + patient life> patient life>+ + acceptable treatment frequency synthesizer to develop: Acceptable treatment frequency synthesizer developed: can be combined with individual patient clinical PK characteristics, objective and demand different treatment The goal is to choose a preventive treatment plan that is suitable for the frequency and dose of the patient's medication

Step4: Predict subclinical bleeding Step4: Predict subclinical bleeding
• AUC is of great significance to the judgment of subclinical bleeding: AUC value is reduced but no clinical bleeding symptoms: It indicates that there may be subclinical bleeding, which needs to be further confirmed by imaging examination
  .
  
• PK Monitoring frequency: recommended 12 pediatric patients under the age of, at least once every six months PK monitoring , adolescents and adults is recommended once a year
  .
  
• AUC is of great significance to the judgment of subclinical bleeding: AUC value is reduced but no clinical bleeding symptoms: It indicates that there may be subclinical bleeding, which needs to be further confirmed by imaging examination
  .
  
AUC AUC is of great significance for the judgment of subclinical bleeding: the judgment of subclinical bleeding is of great significance: AUC value is reduced but no clinical bleeding symptoms: It indicates that there may be subclinical bleeding, and imaging examination is needed for further confirmation
.

• PK Monitoring frequency: recommended 12 pediatric patients under the age of, at least once every six months PK monitoring , adolescents and adults is recommended once a year
  .
  
PK PK monitoring frequency: Monitoring frequency: It is recommended that children under the age of 12 undergo PK monitoring at least once every six months , and adolescents and adults are recommended to perform PK monitoring once a year
.
PK monitoring is carried out every six months and once a year

2.
On-demand treatment and perioperative treatment

2.
On-demand treatment and perioperative treatment 2.
On-demand treatment and perioperative treatment 2.
On-demand treatment and perioperative treatment
• PK software help: by PK help develop individualized on-demand computing or perioperative treatment plan software
  .
  
• Treatment principle: In order to ensure the hemostasis of breakthrough bleeding and the safety of the operation, the factor activity must be maintained above a specific level for a certain period of time until the bleeding is completely stopped or the surgical wound is completely healed
  .
  
• Important PK parameters: Most dosing regimens are mainly determined based on IVR and t _1/2 .
  
  
• PK software help: by PK help develop individualized on-demand computing or perioperative treatment plan software
  .
  
PK PK Software help: Software help: by PK help develop individualized on-demand computing or perioperative treatment plan software
.

• Treatment principle: In order to ensure the hemostasis of breakthrough bleeding and the safety of the operation, the factor activity must be maintained above a specific level for a certain period of time until the bleeding is completely stopped or the surgical wound is completely healed
  .
  
Treatment principle: Treatment principle: In order to ensure the hemostasis of breakthrough bleeding and the safety of the operation, the factor activity must be maintained above a certain level for a certain period of time until the bleeding is completely stopped or the surgical wound is completely healed
.
It is necessary to maintain the factor activity above a certain level for a certain period of time until the bleeding is completely stopped or the surgical wound is completely healed
.

• Important PK parameters: Most dosing regimens are mainly determined based on IVR and t _1/2 .
  
  
Important important PK PK parameters: Parameters: Most dosing regimens are mainly determined based on IVR and t _{1/2 1/2} .



3.
Evaluation of the efficacy of immune tolerance induction (ITI)

3.
Evaluation of the efficacy of immune tolerance induction (ITI) 3.
3.
Evaluation of the efficacy of immune tolerance induction (ITI)
• PK parameters evaluate the efficacy of ITI in patients: specific criteria require that inhibitors continue to be negative (<0.
  6 BU/mL) , and F Ⅷ IVR>66 %, t _1/2 >6 hours
  .
  If the Bethesda detection result of the female sex, recommend regular (at least .
  3 months) for a PK detection, of order F effective monitoring Ⅷ inhibitor
  .
  
• PK parameters evaluate the efficacy of ITI in patients: specific criteria require that inhibitors continue to be negative (<0.
  6 BU/mL) , and F Ⅷ IVR>66 %, t _1/2 >6 hours
  .
  If the Bethesda detection result of the female sex, recommend regular (at least .
  3 months) for a PK detection, of order F effective monitoring Ⅷ inhibitor
  .
  
PK PK parameters to evaluate patient parameters to evaluate the efficacy of ITI ITI : efficacy: specific criteria require that inhibitors continue to be negative (<0.
6 BU/mL) , and F Ⅷ IVR>66 %, t _1/2 >6 _1/2 hours
.
If the Bethesda detection result of the female sex, sex, recommend regular (at least .
3 months) for a PK detection, of order F effective monitoring Ⅷ inhibitor
.
It is recommended to conduct a PK test regularly (at least every 3 months) to effectively monitor F Ⅷ inhibitors .
Point 4: PK-guided hemophilia A treatment benefits Point 4: PK-guided hemophilia A treatment benefits

• lannazzo other studies : compared to the standard treatment, using software PK-directed individualized treatment plan can be patient in joint bleeding rate from 1.
  012 to reduce times to 0.
  845 times , and for each patient annually save 5197 pounds
  .
  
• Pasca et al.
  study : The individualized treatment guided by PK software can specifically adjust the frequency and dose of FⅧ infusion, reduce bleeding, and improve the quality of life
  .
  
• Brekkan et al.
  study : Compared with the standard dosage regimen, adult patients using PK-guided preventive treatment reduced the dosage of FⅧ by 75%, suggesting that PK- guided preventive treatment can significantly reduce the dosage of F Ⅷ and save the cost of F Ⅷ
  .
  
• Domestic research : Compared with low-dose preventive treatment, PK-adjusted preventive treatment reduces the annual joint bleeding rate from 7.
  8 to 1.
  4 times, which significantly improves the therapeutic effect
  .
  
• lannazzo other studies : compared to the standard treatment, using software PK-directed individualized treatment plan can be patient in joint bleeding rate from 1.
  012 to reduce times to 0.
  845 times , and for each patient annually save 5197 pounds
  .
  
lannazzo other studies : compared to the standard treatment, using software PK-directed individualized treatment plan can be patient in joint bleeding rate from 1.
012 to reduce times to 0.
845 times , and for each patient annually save 5197 pounds
.
Lannazzo and other studies : The annual joint bleeding rate was reduced from 1.
012 to 0.
845 , saving 5197 pounds
.

• Pasca et al.
  study : The individualized treatment guided by PK software can specifically adjust the frequency and dose of FⅧ infusion, reduce bleeding, and improve the quality of life
  .
  
Pasca et al.
study : The individualized treatment guided by PK software can specifically adjust the frequency and dose of FⅧ infusion, reduce bleeding, and improve the quality of life
.
Pasca and other studies : reduce bleeding and improve quality of life
.

• Brekkan et al.
  study : Compared with the standard dosage regimen, adult patients using PK-guided preventive treatment reduced the dosage of FⅧ by 75%, suggesting that PK- guided preventive treatment can significantly reduce the dosage of F Ⅷ and save the cost of F Ⅷ
  .
  
Brekkan et al.
study : Compared with the standard dosage regimen, adult patients using PK-guided preventive treatment reduced the dosage of FⅧ by 75%, suggesting that PK- guided preventive treatment can significantly reduce the dosage of F Ⅷ and save the cost of F Ⅷ
.
Brekkan et al.
study : It is suggested that PK- guided preventive treatment can significantly reduce the dosage of F Ⅷ and save the cost of F Ⅷ
.

• Domestic research : Compared with low-dose preventive treatment, PK-adjusted preventive treatment reduces the annual joint bleeding rate from 7.
  8 to 1.
  4 times, which significantly improves the therapeutic effect
  .
  
Domestic research : Compared with low-dose preventive treatment, PK-adjusted preventive treatment reduces the annual joint bleeding rate from 7.
8 to 1.
4 times, which significantly improves the therapeutic effect
.
Domestic research : significantly improve the treatment effect
.


In summary, PK parameters can help clinicians better formulate individualized treatment plans and improve the treatment effect and quality of life of patients with hemophilia
.
Hemophilia doctors need to fully understand the concept of PK analysis , apply PK guidance in clinical practice and combine the comprehensive assessment of the needs of patients with various factors to realize the true personalization of hemophilia treatment
.


In summary, PK parameters can help clinicians better formulate individualized treatment plans and improve the treatment effect and quality of life of patients with hemophilia
.
Hemophilia doctors need to fully understand the concept of PK analysis , apply PK guidance
in clinical practice and combine the comprehensive assessment of the needs of patients with various factors to realize the true personalization of hemophilia treatment .
In summary, PK parameters can help clinicians better formulate individualized treatment plans and improve the treatment effect and quality of life of patients with hemophilia
.
Hemophilia doctors need to fully understand the concept of PK analysis , apply PK guidance
in clinical practice and combine the comprehensive assessment of the needs of patients with various factors to realize the true personalization of hemophilia treatment .
In summary, PKparameters can help clinicians better formulate individualized treatment plans and improve the treatment effect and quality of life of patients with hemophilia
.
Hemophilia doctors need to fully understandthe concept ofPKanalysis, applyPKguidance
in clinical practiceand combine the comprehensive assessment of the needs of patients with various factors to realize the true personalized treatment of hemophilia.


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