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DOI: 10.1055/a-1376-0970
A Practical, One-Clinic Visit Protocol for Pharmacokinetic Profile Generation with the ADVATE myPKFiT Dosing Tool in Severe Hemophilia A Subjects
Funding This research was funded by an Investigator Initiated Research Grant from Baxalta U.S. Inc., a Takeda company, Lexington, Massachusetts (Grant ID number: #IIRH15–27025), with The Hospital for Sick Children as the sponsor site.Abstract
Standard pharmacokinetic (PK) assessments are demanding for persons with hemophilia A, requiring a 72-hour washout and 5 to 11 timed blood samples. A no-washout, single-clinic visit, sparse sampling population PK (PPK) protocol is an attractive alternative. Here, we compared PK parameters obtained with a traditional washout, 6-sampling time point PPK protocol with a no-washout, single-clinic visit, reverse 2-sampling time point PPK protocol in persons with severe hemophilia A (SHA) receiving ADVATE. A total of 39 inhibitor-negative males with SHA (factor VIII activity [FVIII:C] < 2%) were enrolled in a prospective sequential design PK study. Participants completed a washout, 6-sampling time point PPK protocol as well as a no-washout, reverse 2-sampling time point protocol, with samples taken during a single 3-hour clinic visit 24 hours post home infusion of FVIII and then 3 hours post infusion in clinic. FVIII:C levels were analyzed by one-stage and chromogenic assays; blood group and von Willebrand factor antigen (VWF:Ag) were determined; and PK parameters were analyzed using the ADVATE myPKFiT dosing tool. There was moderate to almost perfect agreement for the PK parameters obtained with the 2- and the 6- point PPK protocols using a one-stage FVIII:C assay and a substantial to almost perfect agreement using a chromogenic FVIII:C assay. Significant associations between specific PK parameters and blood group and VWF:Ag were observed. The no-washout, single-clinic visit, reverse 2-sampling time point PPK protocol can be used in the routine clinical setting since it demonstrates sufficient accuracy compared with the more demanding and less practical washout, 6-sampling time point PPK protocol in persons with SHA receiving ADVATE.
Publication History
Received: 08 July 2020
Accepted: 23 January 2021
Accepted Manuscript online:
27 January 2021
Article published online:
14 April 2021
© 2021. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)
Georg Thieme Verlag KG
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References
- 1 Ljung R, Gretenkort Andersson N. The current status of prophylactic replacement therapy in children and adults with haemophilia. Br J Haematol 2015; 169 (06) 777-786
- 2 Collins PW, Blanchette VS, Fischer K. et al; rAHF-PFM Study Group. Break-through bleeding in relation to predicted factor VIII levels in patients receiving prophylactic treatment for severe hemophilia A. J Thromb Haemost 2009; 7 (03) 413-420
- 3 Björkman S, Folkesson A, Jönsson S. Pharmacokinetics and dose requirements of factor VIII over the age range 3-74 years: a population analysis based on 50 patients with long-term prophylactic treatment for haemophilia A. Eur J Clin Pharmacol 2009; 65 (10) 989-998
- 4 Lee M, Morfini M, Schulman S, Ingerslev J. The Factor VIII/Factor IX Scientific and Standardization Committee of the International Society for Thrombosis and Haemostasis: the design and analysis of pharmacokinetic studies of coagulation factors. 2001 . Accessed February 11, 2021 at: https://cdn.ymaws.com/www.isth.org/resource/group/d4a6f49a-f4ec-450f-9e0f-7be9f0c2ab2e/official_communications/fviiipharmaco.pdf
- 5 Morfini M, Lee M, Messori A. The design and analysis of half-life and recovery studies for factor VIII and factor IX. Factor VIII/Factor IX Scientific and Standardization Committee of the International Society for Thrombosis and Haemostasis. Thromb Haemost 1991; 66 (03) 384-386
- 6 Collins PW, Fischer K, Morfini M, Blanchette VS, Björkman S. International Prophylaxis Study Group Pharmacokinetics Expert Working Group. Implications of coagulation factor VIII and IX pharmacokinetics in the prophylactic treatment of haemophilia. Haemophilia 2011; 17 (01) 2-10
- 7 Mingot-Castellano ME, Parra R, Núñez R, Martorell M. Improvement in clinical outcomes and replacement factor VIII use in patients with haemophilia A after factor VIII pharmacokinetic-guided prophylaxis based on Bayesian models with myPKFiT® . Haemophilia 2018; 24 (05) e338-e343
- 8 Sheiner LB, Rosenberg B, Marathe VV. Estimation of population characteristics of pharmacokinetic parameters from routine clinical data. J Pharmacokinet Biopharm 1977; 5 (05) 445-479
- 9 Yu JK, Iorio A, Edginton AN. WAPPS co‐investigators. Using pharmacokinetics for tailoring prophylaxis in people with hemophilia switching between clotting factor products: a scoping review. Res Pract Thromb Haemost 2019; 3 (03) 528-541
- 10 Ette EI, Williams PJ. Population pharmacokinetics I: background, concepts, and models. Ann Pharmacother 2004; 38 (10) 1702-1706
- 11 Björkman S, Oh M, Spotts G. et al. Population pharmacokinetics of recombinant factor VIII: the relationships of pharmacokinetics to age and body weight. Blood 2012; 119 (02) 612-618
- 12 Iorio A, Blanchette V, Blatny J, Collins P, Fischer K, Neufeld E. Estimating and interpreting the pharmacokinetic profiles of individual patients with hemophilia A or B using a population pharmacokinetic approach: communication from the SSC of the ISTH. J Thromb Haemost 2017; 15 (12) 2461-2465
- 13 Hazendonk HCAM, van Moort I, Mathôt RAA. et al; OPTI-CLOT study group. Setting the stage for individualized therapy in hemophilia: What role can pharmacokinetics play?. Blood Rev 2018; 32 (04) 265-271
- 14 Toutain PL, Bousquet-Mélou A. Plasma terminal half-life. J Vet Pharmacol Ther 2004; 27 (06) 427-439
- 15 Blanchette VS, Shapiro AD, Liesner RJ. et al; rAHF-PFM Clinical Study Group. Plasma and albumin-free recombinant factor VIII: pharmacokinetics, efficacy and safety in previously treated pediatric patients. J Thromb Haemost 2008; 6 (08) 1319-1326
- 16 Tarantino MD, Collins PW, Hay CR. et al; RAHF-PFM Clinical Study Group. Clinical evaluation of an advanced category antihaemophilic factor prepared using a plasma/albumin-free method: pharmacokinetics, efficacy, and safety in previously treated patients with haemophilia A. Haemophilia 2004; 10 (05) 428-437
- 17 Fleiss JL, Cohen J. The equivalence of weighted kappa and the intraclass correlation coefficient as measures of reliability. Educ Psychol Meas 1973; 33: 613-619
- 18 Landis JR, Koch GG. The measurement of observer agreement for categorical data. Biometrics 1977; 33 (01) 159-174
- 19 Akoglu H. User's guide to correlation coefficients. Turk J Emerg Med 2018; 18 (03) 91-93
- 20 Björkman S, Blanchette VS, Fischer K. et al; Advate Clinical Program Group. Comparative pharmacokinetics of plasma- and albumin-free recombinant factor VIII in children and adults: the influence of blood sampling schedule on observed age-related differences and implications for dose tailoring. J Thromb Haemost 2010; 8 (04) 730-736
- 21 Pasca S, Milan M, Sarolo L, Zanon E. PK-driven prophylaxis versus standard prophylaxis: when a tailored treatment may be a real and achievable cost-saving approach in children with severe hemophilia A. Thromb Res 2017; 157: 58-63
- 22 Nagao A, Yeung CHT, Germini F, Suzuki T. Clinical outcomes in hemophilia A patients undergoing tailoring of prophylaxis based on population-based pharmacokinetic dosing. Thromb Res 2019; 173: 79-84
- 23 Stemberger M, Kallenbach F, Schmit E. et al. Impact of adopting population pharmacokinetics for tailoring prophylaxis in haemophilia A patients: a historically controlled observational study. Thromb Haemost 2019; 119 (03) 368-376
- 24 MyPKFiT for Healthcare Professionals-User Manual. 3th ed.. Bannockburn, IL: Baxalta U.S. Inc., an entity of Shire PLC; 2019: 29
- 25 Morfini M, Cinotti S, Bellatreccia A. et al; PMReFacto-AICE Study Group. A multicenter pharmacokinetic study of the B-domain deleted recombinant factor VIII concentrate using different assays and standards. J Thromb Haemost 2003; 1 (11) 2283-2289
- 26 Carcao MD, Chelle P, Clarke E. et al. Comparative pharmacokinetics of two extended half-life FVIII concentrates (Eloctate and Adynovate) in adolescents with hemophilia A: is there a difference?. J Thromb Haemost 2019; 17 (07) 1085-1096
- 27 O'Donnell J, Laffan MA. The relationship between ABO histo-blood group, factor VIII and von Willebrand factor. Transfus Med 2001; 11 (04) 343-351
- 28 Lunghi B, Bernardi F, Martinelli N. et al. Functional polymorphisms in the LDLR and pharmacokinetics of Factor VIII concentrates. J Thromb Haemost 2019; 17 (08) 1288-1296
- 29 Fischer K, Pendu R, van Schooten CJ. et al. Models for prediction of factor VIII half-life in severe haemophiliacs: distinct approaches for blood group O and non-O patients. PLoS One 2009; 4 (08) e6745
- 30 Kepa S, Horvath B, Reitter-Pfoertner S. et al. Parameters influencing FVIII pharmacokinetics in patients with severe and moderate haemophilia A. Haemophilia 2015; 21 (03) 343-350
- 31 Barnes C, Lillicrap D, Pazmino-Canizares J. et al. Pharmacokinetics of recombinant factor VIII (Kogenate-FS®) in children and causes of inter-patient pharmacokinetic variability. Haemophilia 2006; 12 (04) 40-49
- 32 Collins PW, Björkman S, Fischer K. et al. Factor VIII requirement to maintain a target plasma level in the prophylactic treatment of severe hemophilia A: influences of variance in pharmacokinetics and treatment regimens. J Thromb Haemost 2010; 8 (02) 269-275
- 33 Gringeri A, Wolfsegger M, Steinitz KN, Reininger AJ. Recombinant full-length factor VIII (FVIII) and extended half-life FVIII products in prophylaxis--new insight provided by pharmacokinetic modelling. Haemophilia 2015; 21 (03) 300-306
- 34 Carlsson M, Berntorp E, Björkman S, Lethagen S, Ljung R. Improved cost-effectiveness by pharmacokinetic dosing of factor VIII in prophylactic treatment of haemophilia A. Haemophilia 1997; 3 (02) 96-101
- 35 Matucci M, Messori A, Donati-Cori G. et al. Kinetic evaluation of four factor VIII concentrates by model-independent methods. Scand J Haematol 1985; 34 (01) 22-28
- 36 Björkman S. Comparative pharmacokinetics of factor VIII and recombinant factor IX: for which coagulation factors should half-life change with age?. Haemophilia 2013; 19 (06) 882-886
- 37 Hajducek DM, Chelle P, Hermans C. et al. Development and evaluation of the population pharmacokinetic models for FVIII and FIX concentrates of the WAPPS-Hemo project. Haemophilia 2020; 26 (03) 384-400