Real pandemic world results of pharmacokinetic-tailored personalized prophylaxis of bleeds in Polish children and adolescents with severe hemophilia A
IntroductionIn 2020, the new nationwide protocol of prophylaxis in Polish plasma-derived FVIII (pdFVIII) previously treated patients (PTPs) with severe hemophilia A (sHA) was introduced, resulting in the necessity of switching from pdFVIII to recombinant FVIII (octocog-alpha; rFVIII). The study aime...
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Frontiers Media S.A.
2023-02-01
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| Series: | Frontiers in Pediatrics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fped.2023.1084539/full |
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| author | Tomasz Urasiński Klaudia Paczóska Wanda Badowska Halina Bobrowska Łucja Dakowicz Grzegorz Dobaczewski Elżbieta Latos-Grażyńska Grażyna Karolczyk Anna Klukowska Andrzej Kołtan Magdalena Wojdalska Paweł Łaguna Maciej Niedźwiedzki Danuta Pietrys Julia Radoń-Proskura Monika Radwańska Iwona Rurańska Tomasz Szczepański Dariusz Wasiński Irena Woźnica-Karczmarz Karolina Zielezińska Aleksandra Królak Tomasz Ociepa |
| author_facet | Tomasz Urasiński Klaudia Paczóska Wanda Badowska Halina Bobrowska Łucja Dakowicz Grzegorz Dobaczewski Elżbieta Latos-Grażyńska Grażyna Karolczyk Anna Klukowska Andrzej Kołtan Magdalena Wojdalska Paweł Łaguna Maciej Niedźwiedzki Danuta Pietrys Julia Radoń-Proskura Monika Radwańska Iwona Rurańska Tomasz Szczepański Dariusz Wasiński Irena Woźnica-Karczmarz Karolina Zielezińska Aleksandra Królak Tomasz Ociepa |
| author_sort | Tomasz Urasiński |
| collection | DOAJ |
| description | IntroductionIn 2020, the new nationwide protocol of prophylaxis in Polish plasma-derived FVIII (pdFVIII) previously treated patients (PTPs) with severe hemophilia A (sHA) was introduced, resulting in the necessity of switching from pdFVIII to recombinant FVIII (octocog-alpha; rFVIII). The study aimed to: (1) assess the safety of switching from pdFVIII to rFVIII, (2) assess the safety and efficacy of pharmacokinetically based (PK-based) personalized prophylaxis in severe hemophilia A.Patients and methods151 children and adolescents receiving prophylaxis with a standard dose (40 U/kg 3 x weekly) of pdFVIII were included in this study. Annualized bleeding rate (ABR) and annualized joint bleeding rate (AJBR) were analyzed for all patients before enrollment. Using myPKFiT application, pharmacokinetic (PK) analysis followed by the selection of the optimal model of prophylaxis was performed in all patients. Two possible models of prophylaxis (standard-dose rFVIII versus PK-based rFVIII) were discussed, with parents leaving the choice to their decision. Parents reported all episodes of bleeds. Screening for inhibitor was performed every 3 months. ABR and AJBR were prospectively analyzed again after a minimum follow-up time of 26 weeks.Results141/151 (93.4%) patients completed the study. 34 patients decided to continue standard prophylaxis with rFVIII (Group I), whereas 107 were switched to PK-based prophylaxis (Group II). The risk of inhibitor development could be assessed in 137/151 (90.7%) patients. Only 2/137 (1.47%) patients (both on PK-based prophylaxis) developed low-titer inhibitor with its spontaneous elimination. The retrospective analysis of bleeds during the last 12 months of standard pdFVIII prophylaxis revealed that patients who decided to continue standard prophylaxis had historically lower ABR and AJBR than those who started PK-based personalized prophylaxis. After a minimum of 26 weeks, ABR and AJBR improved significantly in both groups. There was no significant difference in ABR and AJBR between Group I and Group II during the follow-up period. However, the rate of reduction of ABR and AJBR was higher in patients on PK-based personalized prophylaxis.Conclusion(1) Switching from pdFVIII to rFVIII (octocog-alpha) in PTPs with sHA is safe, (2) PK-based personalized prophylaxis may decrease ABR and AJBR in children and adolescents with sHA. |
| first_indexed | 2024-04-10T07:37:00Z |
| format | Article |
| id | doaj.art-b937e71489a94a3f929880c7587f2bdc |
| institution | Directory Open Access Journal |
| issn | 2296-2360 |
| language | English |
| last_indexed | 2024-04-10T07:37:00Z |
| publishDate | 2023-02-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Pediatrics |
| spelling | doaj.art-b937e71489a94a3f929880c7587f2bdc2023-02-23T12:40:48ZengFrontiers Media S.A.Frontiers in Pediatrics2296-23602023-02-011110.3389/fped.2023.10845391084539Real pandemic world results of pharmacokinetic-tailored personalized prophylaxis of bleeds in Polish children and adolescents with severe hemophilia ATomasz Urasiński0Klaudia Paczóska1Wanda Badowska2Halina Bobrowska3Łucja Dakowicz4Grzegorz Dobaczewski5Elżbieta Latos-Grażyńska6Grażyna Karolczyk7Anna Klukowska8Andrzej Kołtan9Magdalena Wojdalska10Paweł Łaguna11Maciej Niedźwiedzki12Danuta Pietrys13Julia Radoń-Proskura14Monika Radwańska15Iwona Rurańska16Tomasz Szczepański17Dariusz Wasiński18Irena Woźnica-Karczmarz19Karolina Zielezińska20Aleksandra Królak21Tomasz Ociepa22Department of Pediatrics, Hemato-Oncology and Gastroenterology, Pomeranian Medical University, Szczecin, PolandDepartment of Pediatrics, Hemato-Oncology and Gastroenterology, Pomeranian Medical University, Szczecin, PolandDepartment of Pediatric Oncology and Hematology, School of Medicine, University of Warmia Mazury, Olsztyn, PolandWielkopolska Child Health Center, Poznań, PolandDepartment of Pediatric Oncology and Hematology, Medical University of Białystok, Białystok, PolandDepartment of Bone Marrow Transplantation, Pediatric Oncology and Hematology, Wrocław Medical University, Wrocław, PolandDepartment of Bone Marrow Transplantation, Pediatric Oncology and Hematology, Wrocław Medical University, Wrocław, PolandII Department of Pediatrics, Collegium Medicum, Jan Kochanowski University, Kielce, PolandDepartment of Pediatric Oncology, Hematology and Transplantation, Medical University of Warsaw, Warszawa, PolandDepartment of Pediatrics, Hematology and Oncology, Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, PolandDepartment of Pediatrics, Oncology and Hematology, Medical University of Lodz, Łódź, PolandDepartment of Pediatric Oncology, Hematology and Transplantation, Medical University of Warsaw, Warszawa, Poland0Department of Pediatrics, Hematology and Oncology, Medical University of Gdańsk, Gdańsk, Poland1Department of Pediatric Oncology and Hematology, Collegium Medicum, Jagiellonian University, Kraków, Poland0Department of Pediatrics, Hematology and Oncology, Medical University of Gdańsk, Gdańsk, Poland2Department of Pediatric Oncology and Hematology, College of Medical Sciences, University of Rzeszów, Rzeszów, Poland3Department of Pediatrics, Hematology and Oncology, Medical University of Silesia, Katowice, Poland3Department of Pediatrics, Hematology and Oncology, Medical University of Silesia, Katowice, Poland4Department of Pediatric Hematology and Oncology, Collegium Medicum, University of Zielona Góra, Zielona Góra, Poland5Clinic of Pediatric Hematology and Oncology, Medical University of Lublin, Lublin, PolandDepartment of Pediatrics, Hemato-Oncology and Gastroenterology, Pomeranian Medical University, Szczecin, PolandDepartment of Pediatrics, Hemato-Oncology and Gastroenterology, Pomeranian Medical University, Szczecin, PolandDepartment of Pediatrics, Hemato-Oncology and Gastroenterology, Pomeranian Medical University, Szczecin, PolandIntroductionIn 2020, the new nationwide protocol of prophylaxis in Polish plasma-derived FVIII (pdFVIII) previously treated patients (PTPs) with severe hemophilia A (sHA) was introduced, resulting in the necessity of switching from pdFVIII to recombinant FVIII (octocog-alpha; rFVIII). The study aimed to: (1) assess the safety of switching from pdFVIII to rFVIII, (2) assess the safety and efficacy of pharmacokinetically based (PK-based) personalized prophylaxis in severe hemophilia A.Patients and methods151 children and adolescents receiving prophylaxis with a standard dose (40 U/kg 3 x weekly) of pdFVIII were included in this study. Annualized bleeding rate (ABR) and annualized joint bleeding rate (AJBR) were analyzed for all patients before enrollment. Using myPKFiT application, pharmacokinetic (PK) analysis followed by the selection of the optimal model of prophylaxis was performed in all patients. Two possible models of prophylaxis (standard-dose rFVIII versus PK-based rFVIII) were discussed, with parents leaving the choice to their decision. Parents reported all episodes of bleeds. Screening for inhibitor was performed every 3 months. ABR and AJBR were prospectively analyzed again after a minimum follow-up time of 26 weeks.Results141/151 (93.4%) patients completed the study. 34 patients decided to continue standard prophylaxis with rFVIII (Group I), whereas 107 were switched to PK-based prophylaxis (Group II). The risk of inhibitor development could be assessed in 137/151 (90.7%) patients. Only 2/137 (1.47%) patients (both on PK-based prophylaxis) developed low-titer inhibitor with its spontaneous elimination. The retrospective analysis of bleeds during the last 12 months of standard pdFVIII prophylaxis revealed that patients who decided to continue standard prophylaxis had historically lower ABR and AJBR than those who started PK-based personalized prophylaxis. After a minimum of 26 weeks, ABR and AJBR improved significantly in both groups. There was no significant difference in ABR and AJBR between Group I and Group II during the follow-up period. However, the rate of reduction of ABR and AJBR was higher in patients on PK-based personalized prophylaxis.Conclusion(1) Switching from pdFVIII to rFVIII (octocog-alpha) in PTPs with sHA is safe, (2) PK-based personalized prophylaxis may decrease ABR and AJBR in children and adolescents with sHA.https://www.frontiersin.org/articles/10.3389/fped.2023.1084539/fullhemophilia Aannualized bleeding rateannualized joint bleeding rateplasma-derived FVIIIrecombinant FVIIIbleeding prophylaxis |
| spellingShingle | Tomasz Urasiński Klaudia Paczóska Wanda Badowska Halina Bobrowska Łucja Dakowicz Grzegorz Dobaczewski Elżbieta Latos-Grażyńska Grażyna Karolczyk Anna Klukowska Andrzej Kołtan Magdalena Wojdalska Paweł Łaguna Maciej Niedźwiedzki Danuta Pietrys Julia Radoń-Proskura Monika Radwańska Iwona Rurańska Tomasz Szczepański Dariusz Wasiński Irena Woźnica-Karczmarz Karolina Zielezińska Aleksandra Królak Tomasz Ociepa Real pandemic world results of pharmacokinetic-tailored personalized prophylaxis of bleeds in Polish children and adolescents with severe hemophilia A Frontiers in Pediatrics hemophilia A annualized bleeding rate annualized joint bleeding rate plasma-derived FVIII recombinant FVIII bleeding prophylaxis |
| title | Real pandemic world results of pharmacokinetic-tailored personalized prophylaxis of bleeds in Polish children and adolescents with severe hemophilia A |
| title_full | Real pandemic world results of pharmacokinetic-tailored personalized prophylaxis of bleeds in Polish children and adolescents with severe hemophilia A |
| title_fullStr | Real pandemic world results of pharmacokinetic-tailored personalized prophylaxis of bleeds in Polish children and adolescents with severe hemophilia A |
| title_full_unstemmed | Real pandemic world results of pharmacokinetic-tailored personalized prophylaxis of bleeds in Polish children and adolescents with severe hemophilia A |
| title_short | Real pandemic world results of pharmacokinetic-tailored personalized prophylaxis of bleeds in Polish children and adolescents with severe hemophilia A |
| title_sort | real pandemic world results of pharmacokinetic tailored personalized prophylaxis of bleeds in polish children and adolescents with severe hemophilia a |
| topic | hemophilia A annualized bleeding rate annualized joint bleeding rate plasma-derived FVIII recombinant FVIII bleeding prophylaxis |
| url | https://www.frontiersin.org/articles/10.3389/fped.2023.1084539/full |
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