TY - JOUR
T1 - Occurrence of FVIII Inhibitors in Hemophilia A Patients Following an Institutional Switch to a Third Generation B-Domain-Deleted FVIII
AU - Hooimeijer, Louise H.
AU - Stein-Wit, Marjet A.
AU - Voskuilen, Marja A.J.
AU - Lukens, Michaël V.
AU - Meijer, Karina
AU - Mäkelburg, Anja B.U.
AU - Tamminga, Rienk Y.J.
N1 - Publisher Copyright:
© The Author(s) 2023.
PY - 2023/1
Y1 - 2023/1
N2 - In 2018, Refacto AFR, a B-domain-deleted third-generation FVIII concentrate, became our preferential product. After the introduction, the development of inhibitors was prospectively monitored; retrospectively, we sought for risk factors in the patients who developed a de-novo inhibitor. Over a period of 15 months, 4/19 adult patients with non-severe haemophilia who were treated on demand for surgery, developed high titer antibodies to FVIII after administration of Refacto AFR; 5/52 mostly severe patients on prophylaxis, developed an inhibitor (3 ≥ 0.1 BU; 1 > 0.6 BU, 1 high titre) after they switched to Refacto AFR; all were children <14 years of age and with >100 exposure days, none related to surgery or intensive treatment; all received KovaltryR before. In conclusion: inhibitors were encountered in on demand patients and previously treated prophylaxis patients; this observation might be a coincidental finding, but also risk factors like genotype and surgery and/or that Refacto AFR is more immunogenic should be considered. For the patients on prophylaxis we hypothesize that loss of tolerance by preceding KovaltryR might have contributed to inhibitor development.
AB - In 2018, Refacto AFR, a B-domain-deleted third-generation FVIII concentrate, became our preferential product. After the introduction, the development of inhibitors was prospectively monitored; retrospectively, we sought for risk factors in the patients who developed a de-novo inhibitor. Over a period of 15 months, 4/19 adult patients with non-severe haemophilia who were treated on demand for surgery, developed high titer antibodies to FVIII after administration of Refacto AFR; 5/52 mostly severe patients on prophylaxis, developed an inhibitor (3 ≥ 0.1 BU; 1 > 0.6 BU, 1 high titre) after they switched to Refacto AFR; all were children <14 years of age and with >100 exposure days, none related to surgery or intensive treatment; all received KovaltryR before. In conclusion: inhibitors were encountered in on demand patients and previously treated prophylaxis patients; this observation might be a coincidental finding, but also risk factors like genotype and surgery and/or that Refacto AFR is more immunogenic should be considered. For the patients on prophylaxis we hypothesize that loss of tolerance by preceding KovaltryR might have contributed to inhibitor development.
KW - antibodies
KW - factor VIII concentrate
KW - hemophilia A
KW - immunity
KW - therapeutics
UR - http://www.scopus.com/inward/record.url?scp=85151316349&partnerID=8YFLogxK
U2 - 10.1177/10760296231167416
DO - 10.1177/10760296231167416
M3 - Article
C2 - 36998198
AN - SCOPUS:85151316349
SN - 1076-0296
VL - 29
JO - Clinical and Applied Thrombosis/Hemostasis
JF - Clinical and Applied Thrombosis/Hemostasis
ER -