No immunological changes after factor VIII product switch: An in depth analysis in haemophilia A patients

Sarah J Schep; Kathelijn Fischer; Marianne Boes; Roger E G Schutgens

doi:10.1111/hae.14808

No immunological changes after factor VIII product switch: An in depth analysis in haemophilia A patients

Sarah J Schep, Kathelijn Fischer, Marianne Boes, Roger E G Schutgens

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Abstract

BACKGROUND: A challenging complication in the treatment of haemophilia A is the formation of neutralizing anti-FVIII antibodies (inhibitors). There is ongoing debate on the effect of FVIII product and inhibitor risk, rendering patients and physicians reluctant to switch FVIII-products.

AIM: This study aimed to evaluate changes in the immune profile of haemophilia A patients after switching FVIII products and their possible relation to inhibitor development. Secondary, FVIII efficacy after switching were assessed.

METHODS: Patients, who switched FVIII-products between 2017-2019, were included in this single centre cohort study. Prospective comparison of immunoregulatory cells and markers by flow-cytometry before and after the switch was performed in a subgroup. For the total cohort clinical data regarding inhibitor development and FVIII efficacy 1 year before and after switching were retrospectively collected.

RESULTS: One-hundred patients (including 39 with prospective immunological assessment) were analyzed, of which 31% switched from plasma-derived (pdFVIII) to recombinant standard half-life FVIII (SHL-rFVIII), 47% between different SHL-rFVIII, and 22% from pdFVIII/SHL-rFVIII to rFVIII-Fc. No remarkable changes in immunoregulatory cell functions were observed after switching, regardless the type of switch. None of the patients developed an inhibitor. FVIII efficacy, that is, FVIII usage, half-life and annual bleeding rate (ABR), was similar before and after switch for the SHL products, whereas rFVIII-Fc associated with a longer half-life (13.1 vs. 15.0 h) and lower ABR (3.0 vs. 1.0).

CONCLUSIONS: Switching to a different FVIII product was not associated with inhibitor development, nor with differences in the immune profile. Switching to rFVIII-Fc lead to lower ABR.

Original language	English
Pages (from-to)	1039-1048
Number of pages	10
Journal	Haemophilia
Volume	29
Issue number	4
Early online date	5 Jun 2023
DOIs	https://doi.org/10.1111/hae.14808
Publication status	Published - Jul 2023

Keywords

anti-FVIII antibodies
extended half-life factor VIII
factor VIII
haemophilia A
inhibitor
rFVIII-Fc

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@article{c1e410313cde40be926c00ece512c8bc,

title = "No immunological changes after factor VIII product switch: An in depth analysis in haemophilia A patients",

abstract = "BACKGROUND: A challenging complication in the treatment of haemophilia A is the formation of neutralizing anti-FVIII antibodies (inhibitors). There is ongoing debate on the effect of FVIII product and inhibitor risk, rendering patients and physicians reluctant to switch FVIII-products.AIM: This study aimed to evaluate changes in the immune profile of haemophilia A patients after switching FVIII products and their possible relation to inhibitor development. Secondary, FVIII efficacy after switching were assessed.METHODS: Patients, who switched FVIII-products between 2017-2019, were included in this single centre cohort study. Prospective comparison of immunoregulatory cells and markers by flow-cytometry before and after the switch was performed in a subgroup. For the total cohort clinical data regarding inhibitor development and FVIII efficacy 1 year before and after switching were retrospectively collected.RESULTS: One-hundred patients (including 39 with prospective immunological assessment) were analyzed, of which 31% switched from plasma-derived (pdFVIII) to recombinant standard half-life FVIII (SHL-rFVIII), 47% between different SHL-rFVIII, and 22% from pdFVIII/SHL-rFVIII to rFVIII-Fc. No remarkable changes in immunoregulatory cell functions were observed after switching, regardless the type of switch. None of the patients developed an inhibitor. FVIII efficacy, that is, FVIII usage, half-life and annual bleeding rate (ABR), was similar before and after switch for the SHL products, whereas rFVIII-Fc associated with a longer half-life (13.1 vs. 15.0 h) and lower ABR (3.0 vs. 1.0).CONCLUSIONS: Switching to a different FVIII product was not associated with inhibitor development, nor with differences in the immune profile. Switching to rFVIII-Fc lead to lower ABR.",

keywords = "anti-FVIII antibodies, extended half-life factor VIII, factor VIII, haemophilia A, inhibitor, rFVIII-Fc",

author = "Schep, {Sarah J} and Kathelijn Fischer and Marianne Boes and Schutgens, {Roger E G}",

note = "Funding Information: The authors are thankful to all participants of this study and the staff of the Van Creveldkliniek and Center for Translational Immunology. Publisher Copyright: {\textcopyright} 2023 The Authors. Haemophilia published by John Wiley & Sons Ltd.",

year = "2023",

month = jul,

doi = "10.1111/hae.14808",

language = "English",

volume = "29",

pages = "1039--1048",

journal = "Haemophilia",

issn = "1351-8216",

publisher = "Wiley-Blackwell",

number = "4",

}

TY - JOUR

T1 - No immunological changes after factor VIII product switch

T2 - An in depth analysis in haemophilia A patients

AU - Schep, Sarah J

AU - Fischer, Kathelijn

AU - Boes, Marianne

AU - Schutgens, Roger E G

N1 - Funding Information: The authors are thankful to all participants of this study and the staff of the Van Creveldkliniek and Center for Translational Immunology. Publisher Copyright: © 2023 The Authors. Haemophilia published by John Wiley & Sons Ltd.

PY - 2023/7

Y1 - 2023/7

N2 - BACKGROUND: A challenging complication in the treatment of haemophilia A is the formation of neutralizing anti-FVIII antibodies (inhibitors). There is ongoing debate on the effect of FVIII product and inhibitor risk, rendering patients and physicians reluctant to switch FVIII-products.AIM: This study aimed to evaluate changes in the immune profile of haemophilia A patients after switching FVIII products and their possible relation to inhibitor development. Secondary, FVIII efficacy after switching were assessed.METHODS: Patients, who switched FVIII-products between 2017-2019, were included in this single centre cohort study. Prospective comparison of immunoregulatory cells and markers by flow-cytometry before and after the switch was performed in a subgroup. For the total cohort clinical data regarding inhibitor development and FVIII efficacy 1 year before and after switching were retrospectively collected.RESULTS: One-hundred patients (including 39 with prospective immunological assessment) were analyzed, of which 31% switched from plasma-derived (pdFVIII) to recombinant standard half-life FVIII (SHL-rFVIII), 47% between different SHL-rFVIII, and 22% from pdFVIII/SHL-rFVIII to rFVIII-Fc. No remarkable changes in immunoregulatory cell functions were observed after switching, regardless the type of switch. None of the patients developed an inhibitor. FVIII efficacy, that is, FVIII usage, half-life and annual bleeding rate (ABR), was similar before and after switch for the SHL products, whereas rFVIII-Fc associated with a longer half-life (13.1 vs. 15.0 h) and lower ABR (3.0 vs. 1.0).CONCLUSIONS: Switching to a different FVIII product was not associated with inhibitor development, nor with differences in the immune profile. Switching to rFVIII-Fc lead to lower ABR.

AB - BACKGROUND: A challenging complication in the treatment of haemophilia A is the formation of neutralizing anti-FVIII antibodies (inhibitors). There is ongoing debate on the effect of FVIII product and inhibitor risk, rendering patients and physicians reluctant to switch FVIII-products.AIM: This study aimed to evaluate changes in the immune profile of haemophilia A patients after switching FVIII products and their possible relation to inhibitor development. Secondary, FVIII efficacy after switching were assessed.METHODS: Patients, who switched FVIII-products between 2017-2019, were included in this single centre cohort study. Prospective comparison of immunoregulatory cells and markers by flow-cytometry before and after the switch was performed in a subgroup. For the total cohort clinical data regarding inhibitor development and FVIII efficacy 1 year before and after switching were retrospectively collected.RESULTS: One-hundred patients (including 39 with prospective immunological assessment) were analyzed, of which 31% switched from plasma-derived (pdFVIII) to recombinant standard half-life FVIII (SHL-rFVIII), 47% between different SHL-rFVIII, and 22% from pdFVIII/SHL-rFVIII to rFVIII-Fc. No remarkable changes in immunoregulatory cell functions were observed after switching, regardless the type of switch. None of the patients developed an inhibitor. FVIII efficacy, that is, FVIII usage, half-life and annual bleeding rate (ABR), was similar before and after switch for the SHL products, whereas rFVIII-Fc associated with a longer half-life (13.1 vs. 15.0 h) and lower ABR (3.0 vs. 1.0).CONCLUSIONS: Switching to a different FVIII product was not associated with inhibitor development, nor with differences in the immune profile. Switching to rFVIII-Fc lead to lower ABR.

KW - anti-FVIII antibodies

KW - extended half-life factor VIII

KW - factor VIII

KW - haemophilia A

KW - inhibitor

KW - rFVIII-Fc

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U2 - 10.1111/hae.14808

DO - 10.1111/hae.14808

M3 - Article

C2 - 37276354

SN - 1351-8216

VL - 29

SP - 1039

EP - 1048

JO - Haemophilia

JF - Haemophilia

IS - 4

ER -

No immunological changes after factor VIII product switch: An in depth analysis in haemophilia A patients

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Keywords

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