دورية أكاديمية
Pharmacodynamics Monitoring of Emicizumab in Patients with Hemophilia A.
| العنوان: | Pharmacodynamics Monitoring of Emicizumab in Patients with Hemophilia A. |
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| المؤلفون: | Bertaggia Calderara D; Division of Hematology and Central Hematology Laboratory, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), Lausanne, Switzerland., Marchi Cappelletti R; Department of Genetic Medicine and Development, Faculty of Medicine, University of Geneva, Geneva, Switzerland., Batista Mesquita Sauvage AP; Division of Hematology and Central Hematology Laboratory, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), Lausanne, Switzerland., Durual S; Biomaterials Laboratory, University Clinics of Dental Medicine, University of Geneva, Switzerland., Gomez FJ; Division of Hematology and Central Hematology Laboratory, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), Lausanne, Switzerland., Zermatten MG; Division of Hematology and Central Hematology Laboratory, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), Lausanne, Switzerland., Aliotta A; Division of Hematology and Central Hematology Laboratory, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), Lausanne, Switzerland., Casini A; Department of Medicine, University of Geneva, Geneva, Switzerland.; Division of Angiology and Hemostasis, University Hospitals of Geneva, Geneva, Switzerland., Alberio L; Division of Hematology and Central Hematology Laboratory, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), Lausanne, Switzerland. |
| المصدر: | Thrombosis and haemostasis [Thromb Haemost] 2023 Oct; Vol. 123 (10), pp. 955-965. Date of Electronic Publication: 2023 Jun 19. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Thieme Country of Publication: Germany NLM ID: 7608063 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2567-689X (Electronic) Linking ISSN: 03406245 NLM ISO Abbreviation: Thromb Haemost Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2018- : Stuttgart : Thieme Original Publication: Stuttgart, Schattauer. |
| مواضيع طبية MeSH: | Hemophilia A* , Antibodies, Bispecific*/pharmacology , Antibodies, Bispecific*/therapeutic use , Hemostatics*/therapeutic use, Adult ; Humans ; Factor VIII ; Thrombin ; Fibrin |
| مستخلص: | Background: Emicizumab is a bispecific antibody mimicking coagulation factor VIII (FVIII) employed to treat patients with hemophilia A (PwHA) regardless of FVIII inhibitor status. The identification of biological markers reflecting the hemostatic competence of patients under emicizumab therapy would have a great clinical value. Unfortunately, emicizumab over-corrects standard coagulation assays, precluding their use for evaluating the hemostatic correction achieved in vivo . Here, we investigated whether global coagulation assays (GCA) would allow monitoring the biological response to non-factor replacement therapy with emicizumab. Materials and Methods: Six adults PwHA received a weekly dose of emicizumab of 3 mg/kg during weeks (W) 1 4 and 1.5 mg/kg from W5 onwards. Response to treatment was monitored weekly by emicizumab plasma concentration, thrombin generation (TG), and fibrin clot formation (FCF) and structure. TG and FCF results were compared to patient baseline, FVIII replacement, and healthy donors. Results: TG and FCF significantly increased in PwHA after the loading period, reaching a plateau that lasted until the end of monitoring. Similarly, fibrin clot network became denser with thinner fibrin fibers. However, TG contrary to FCF remained at the lower limits of reference values. Remarkably, despite having similar plateau concentrations of emicizumab some patients showed markedly different degrees of TG and FCF improvement. Conclusion: Our study enriches the knowledge on the use of GCA to monitor non-factor replacement therapy, indicating that TG and FCF could act as direct markers of emicizumab biological activity. GCA allow to capture and visualize the individually variable response to emicizumab, leading a step forward to the personalization of patient treatment. Competing Interests: D.B.C. declares financial support from the Swiss Hemophilia Network for this study; in addition she declares financial support from Bayer and CSL Behring for lectures; from Bayer, NovoNordisk, and SOBI for attending scientific meetings. L.A. declares financial support from Roche for this study; in addition he declares financial support from Bayer, CSL Behring, NovoNordisk, Octapharma, Roche, and SOBI for the clinical haemophilia program; from Bayer, CSL Behring, Sanofi, Takeda/Shire, and Werfen for lectures; from Biotest, NovoNordisk, and SOBI for attending scientific meeting; from Novartis, NovoNordisk, Sanofi, SOBI, and Werfen for participation in Advisory Boards. (Thieme. All rights reserved.) |
| معلومات مُعتمدة: | SNF 320030-197392 Switzerland SNSF_ Swiss National Science Foundation |
| المشرفين على المادة: | 7NL2E3F6K3 (emicizumab) 9001-27-8 (Factor VIII) 0 (Antibodies, Bispecific) 0 (Hemostatics) EC 3.4.21.5 (Thrombin) 9001-31-4 (Fibrin) |
| تواريخ الأحداث: | Date Created: 20230619 Date Completed: 20230928 Latest Revision: 20230928 |
| رمز التحديث: | 20240628 |
| DOI: | 10.1055/s-0043-1769788 |
| PMID: | 37336473 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 2567-689X |
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| DOI: | 10.1055/s-0043-1769788 |