Using pharmacokinetics for tailoring prophylaxis in people with hemophilia switching between clotting factor products: A scoping review

Yu, Jacky K.; Iorio, Alfonso; Edginton, Andrea N.; co‐investigators, Wapps

doi:10.1002/rth2.12204

Cited by 19 publications

(18 citation statements)

References 60 publications

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“…PWHs on prophylaxis with standard FVIII concentrates, two to three times per week, have usually a FVIII trough level of 1 to 2%. 31 The same FIX trough level is obtained with standard FIX concentrates administered once or twice per week. These trough levels are certainly insufficient to effectively protect against bleeding events during antithrombotic treatments, and should be increased at least above 5% or even 10%, depending on the antithrombotic treatment type.…”

Section: Discussionmentioning

confidence: 86%

“…FVIII/FIX EHL concentrates could help to achieve these trough target levels without increasing the number of infusions. 31 32 33 In the recent guidelines for antithrombotic treatments in PWHs, the minimum FVIII/FIX trough levels for SAPT range from 1 to 5%. 13 14 15 For AC (and DAPT), the recommended FVIII/FIX trough level is ≥30%.…”

Section: Discussionmentioning

confidence: 99%

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Long-Term Antithrombotic Treatments Prescribed for Cardiovascular Diseases in Patients with Hemophilia: Results from the French Registry

Guillet

Cayla

Lebreton³

et al. 2020

Thromb Haemost

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Cardiovascular diseases (CVDs) are a major issue in aging patients with hemophilia (PWHs). Antithrombotic agents are widely used in the general population for CVD treatment, but this recommendation is not fully applicable to PWHs. To improve treatment strategies, a prospective case–control study (COCHE) that analyzed CVD management and follow-up (2 years/patient) in PWHs was performed in France from 2011 to 2018. In total, 68 PWHs (median age: 65 years [39–89]; 48 mild, 10 moderate, and 10 severe hemophilia) were included (n = 50 with acute coronary syndrome, n = 17 with atrial fibrillation, n = 1 with both). They were matched with 68 control PWHs without antithrombotic treatment. In our series, bleeding was significantly influenced by (1) hemophilia severity, with a mean annualized bleeding ratio significantly higher in COCHE patients than in controls with basal clotting factor level up to 20%, (2) antihemorrhagic regimen (on-demand vs. prophylaxis) in severe (hazard ratio [HR] = 16.69 [95% confidence interval, CI: 8.2–47.26]; p < 0.0001) and moderate hemophilia (HR = 42.43 [95% CI: 1.86–966.1]; p = 0.0028), (3) type of antithrombotic treatment in mild hemophilia, with a significantly higher risk of bleeding in COCHE patients than in controls for dual-pathway therapy (HR = 15.64 [95% CI: 1.57–115.8]; p = 0.019), anticoagulant drugs alone (HR = 9.91 [95% CI: 1.34–73.47]; p = 0.0248), dual antiplatelet therapy (HR = 5.31 [95% CI: 1.23–22.92]; p = 0.0252), and single antiplatelet therapy (HR = 3.76 [95% CI: 1.13–12.55]; p = 0.0313); and (4) HAS-BLED score ≥3 (odds ratio [OR] = 33 [95% CI: 1.43–761.2]; p = 0.0065). Gastrointestinal bleeding was also significantly higher in COCHE patients than in controls (OR = 15 [95% CI: 1.84–268]; p = 0.0141). The COCHE study confirmed that antithrombotic treatments in PWHs are associated with increased bleeding rates in function of hemophilia-specific factors and also of known factors in the general population.

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Section: Discussionmentioning

confidence: 86%

Section: Discussionmentioning

confidence: 99%

Long-Term Antithrombotic Treatments Prescribed for Cardiovascular Diseases in Patients with Hemophilia: Results from the French Registry

Guillet

Cayla

Lebreton³

et al. 2020

Thromb Haemost

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“…Systematic reviews, on the other hand, require specific study types, such as randomized control trials, that must meet certain quality standards in order to be included 13 . Scoping reviews have been useful in providing clinical guidance in the management of disorders on which individual studies may be insufficient to suggest therapeutic approaches, while a summation of available data may be used to provide useful recommendations 15‐17 . For a rare disorder such as AVWS‐MGUS where there is a paucity of large studies, and data are limited to case reports or small series of different designs, a scoping review was the more appropriate approach for our study.…”

Section: Introductionmentioning

confidence: 99%

Acquired von Willebrand syndrome in monoclonal gammopathy – A scoping review on hemostatic management

Abou‐Ismail

Rodgers

Bray

et al. 2021

Research and Practice in Thrombosis and Haemostasis

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Background Acquired von Willebrand syndrome (AVWS) has been associated with monoclonal gammopathy of undetermined significance (MGUS), with limited data on its management. Methods We conducted a systematic literature search in Medline (Ovid), Embase, and Scopus up to September 11, 2019, for studies reporting on the management of AVWS associated with MGUS (AVWS‐MGUS). Data on patient characteristics, laboratory parameters at presentation, and clinical and laboratory outcomes were extracted. Objectives To describe the clinical presentation and outcomes of different therapeutic approaches. Results Seventy‐five studies were included in the final review, for a total of 137 patients. Most patients had von Willebrand factor ristocetin cofactor activity <30 IU/dL (86.6%) and factor VIII levels <50 IU/dL (91.8%). Bleeding severity ranged from no bleeding (16.1%) to minor bleeding (46.4%) and major bleeding (37.5%). The overall clinical success rates for 1‐deamino‐8‐D‐arginine vasopressin (DDAVP), factor replacement therapy, and intravenous immunoglobulin (IVIG) were 43.8%, 33.3%, and 85.4%, respectively. The laboratory response rates for DDAVP, factor replacement therapy, and IVIG were 39.0%, 62.9%, and 88.6%, respectively. Several other treatments were also reported in small numbers, out of which myeloma‐directed therapies, plasma exchange, recombinant factor VIIa, and antifibrinolytics appeared most successful, while immunosuppressive agents were largely ineffective. Conclusion IVIG appears to be an effective treatment for AVWS‐MGUS bleeding, conferring a high clinical success rate with measurable laboratory outcomes; albeit temporary. DDAVP and factor replacement therapy may be partially successful in controlling minor bleeds, but not major bleeds. Other less commonly used agents may be effective in certain cases, although data are limited.

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“…As biopharmaceuticals, FVIII concentrates may be biosimilar, but they are not bioequivalent 19 . Several hemophilia studies have demonstrated that when individuals switch from one factor concentrate to another, the average PK parameters can be similar, but individuals can have very different concentration‐time profiles on the two products 19‐21 .…”

Section: Discussionmentioning

confidence: 99%

Extended half‐life factor VIII concentrates in adults with hemophilia A: Comparative pharmacokinetics of two products

Teitel

Sholzberg

Iorio

2021

Research and Practice in Thrombosis and Haemostasis

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Background The use of pharmacokinetic (PK) studies to help design personalized prophylaxis regimens for factor VIII (FVIII) concentrate in individuals with hemophilia A has been recognized for many years but only became practical for routine clinical use with the availability of web‐accessible population PK applications based on Bayesian analysis. Objective To compare PK variables using population PK studies done on 2 extended half‐life recombinant FVIII concentrates in 23 individuals with hemophilia A after switching from one product to the other. Methods We retrospectively analyzed PK parameters derived from the Web‐Accessible Population Pharmacokinetic Service‐Hemophilia (WAPPS‐HEMO) application on 23 individuals with severe or moderately severe hemophilia A who were required to switch from recombinant FVIII Fc (Eloctate; Biogen, Cambridge, MA, USA) to recombinant antihemophilic factor PEGylated (Adynovate; Takeda Pharmaceutical Company, Osaka, Japan) between 2016 and 2017. Results There were minor PK differences between Eloctate and Adynovate, but some parameters did reach statistical significance, namely in vivo recovery (mean, 2.73 IU/dL per IU/kg vs 2.41 IU/dL per IU/kg), clearance (mean, 0.163 mL/h vs 0.194 mL/h), and volume of distribution at steady state (mean, 42.5 ml/kg vs 49.8 mL/kg). Smaller nonsignificant trends toward higher values for Adynovate were seen in terminal half‐life, area under the curve, and predicted times to 5% and 1% residual FVIII after infusion. Conclusion Population PK analysis revealed differences between the two extended half‐life FVIII concentrates, reaching significance for in vivo recovery, clearance, and volume of distribution.

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Using pharmacokinetics for tailoring prophylaxis in people with hemophilia switching between clotting factor products: A scoping review

Cited by 19 publications

References 60 publications

Long-Term Antithrombotic Treatments Prescribed for Cardiovascular Diseases in Patients with Hemophilia: Results from the French Registry

Long-Term Antithrombotic Treatments Prescribed for Cardiovascular Diseases in Patients with Hemophilia: Results from the French Registry

Acquired von Willebrand syndrome in monoclonal gammopathy – A scoping review on hemostatic management

Extended half‐life factor VIII concentrates in adults with hemophilia A: Comparative pharmacokinetics of two products

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