Current and future approaches to inhibitor management and aversion

Charles Hay, Michael Recht, Manuel Carcao, Birgit Reipert

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Immune tolerance induction (ITI) is the most common approach used to eliminate inhibitors that develop in hemophilia A patients following exposure to factor (F) VIII therapy. ITI generally requires ongoing long-term exposure to factor replacement therapy using FVIII or FIX. Although plasma-derived products have been the mainstay of ITI therapy in the past, recent data indicate that high-purity (i.e., recombinant) rFVIII products are probably equally effective. For patients who have failed to respond to ITI treatment, or for those at high risk to do so, immunosuppressive therapy may be helpful. Rituximab has demonstrated a possible clinical benefit in hemophilic and nonhemophilic patients developing FVIII inhibitors, but benefit in those with congenital hemophilia and inhibitors has not been established and more extensive clinical studies are needed. More recently, research on reducing the incidence of inhibitor development has included mutagenizing key epitopes of the FVIII antigenic molecule to alter its immunogenicity without affecting biological activity, as well as induction of tolerance by gene therapy with immunodominant A2 and C2 domains of FVIII presented by B cells as immunoglobulin fusion proteins.

Original languageEnglish (US)
Pages (from-to)15-21
Number of pages7
JournalSeminars in Thrombosis and Hemostasis
Volume32
Issue numberSUPPL. 2
DOIs
StatePublished - Jun 2006
Externally publishedYes

Fingerprint

Immune Tolerance
Hemophilia A
Therapeutics
Immunodominant Epitopes
Factor VIII
Immunosuppressive Agents
varespladib methyl
Genetic Therapy
Immunoglobulins
Epitopes
B-Lymphocytes
Incidence
Research
Proteins

Keywords

  • Congenital hemophilia
  • Gene therapy
  • Immune tolerance induction (ITI)
  • Immunosuppressive therapy
  • Rituximab

ASJC Scopus subject areas

  • Hematology
  • Cardiology and Cardiovascular Medicine

Cite this

Current and future approaches to inhibitor management and aversion. / Hay, Charles; Recht, Michael; Carcao, Manuel; Reipert, Birgit.

In: Seminars in Thrombosis and Hemostasis, Vol. 32, No. SUPPL. 2, 06.2006, p. 15-21.

Research output: Contribution to journalArticle

Hay, Charles ; Recht, Michael ; Carcao, Manuel ; Reipert, Birgit. / Current and future approaches to inhibitor management and aversion. In: Seminars in Thrombosis and Hemostasis. 2006 ; Vol. 32, No. SUPPL. 2. pp. 15-21.
@article{fd067b0bfff04826a641b9a726012b9a,
title = "Current and future approaches to inhibitor management and aversion",
abstract = "Immune tolerance induction (ITI) is the most common approach used to eliminate inhibitors that develop in hemophilia A patients following exposure to factor (F) VIII therapy. ITI generally requires ongoing long-term exposure to factor replacement therapy using FVIII or FIX. Although plasma-derived products have been the mainstay of ITI therapy in the past, recent data indicate that high-purity (i.e., recombinant) rFVIII products are probably equally effective. For patients who have failed to respond to ITI treatment, or for those at high risk to do so, immunosuppressive therapy may be helpful. Rituximab has demonstrated a possible clinical benefit in hemophilic and nonhemophilic patients developing FVIII inhibitors, but benefit in those with congenital hemophilia and inhibitors has not been established and more extensive clinical studies are needed. More recently, research on reducing the incidence of inhibitor development has included mutagenizing key epitopes of the FVIII antigenic molecule to alter its immunogenicity without affecting biological activity, as well as induction of tolerance by gene therapy with immunodominant A2 and C2 domains of FVIII presented by B cells as immunoglobulin fusion proteins.",
keywords = "Congenital hemophilia, Gene therapy, Immune tolerance induction (ITI), Immunosuppressive therapy, Rituximab",
author = "Charles Hay and Michael Recht and Manuel Carcao and Birgit Reipert",
year = "2006",
month = "6",
doi = "10.1055/s-2006-946910",
language = "English (US)",
volume = "32",
pages = "15--21",
journal = "Seminars in Thrombosis and Hemostasis",
issn = "0094-6176",
publisher = "Thieme Medical Publishers",
number = "SUPPL. 2",

}

TY - JOUR

T1 - Current and future approaches to inhibitor management and aversion

AU - Hay, Charles

AU - Recht, Michael

AU - Carcao, Manuel

AU - Reipert, Birgit

PY - 2006/6

Y1 - 2006/6

N2 - Immune tolerance induction (ITI) is the most common approach used to eliminate inhibitors that develop in hemophilia A patients following exposure to factor (F) VIII therapy. ITI generally requires ongoing long-term exposure to factor replacement therapy using FVIII or FIX. Although plasma-derived products have been the mainstay of ITI therapy in the past, recent data indicate that high-purity (i.e., recombinant) rFVIII products are probably equally effective. For patients who have failed to respond to ITI treatment, or for those at high risk to do so, immunosuppressive therapy may be helpful. Rituximab has demonstrated a possible clinical benefit in hemophilic and nonhemophilic patients developing FVIII inhibitors, but benefit in those with congenital hemophilia and inhibitors has not been established and more extensive clinical studies are needed. More recently, research on reducing the incidence of inhibitor development has included mutagenizing key epitopes of the FVIII antigenic molecule to alter its immunogenicity without affecting biological activity, as well as induction of tolerance by gene therapy with immunodominant A2 and C2 domains of FVIII presented by B cells as immunoglobulin fusion proteins.

AB - Immune tolerance induction (ITI) is the most common approach used to eliminate inhibitors that develop in hemophilia A patients following exposure to factor (F) VIII therapy. ITI generally requires ongoing long-term exposure to factor replacement therapy using FVIII or FIX. Although plasma-derived products have been the mainstay of ITI therapy in the past, recent data indicate that high-purity (i.e., recombinant) rFVIII products are probably equally effective. For patients who have failed to respond to ITI treatment, or for those at high risk to do so, immunosuppressive therapy may be helpful. Rituximab has demonstrated a possible clinical benefit in hemophilic and nonhemophilic patients developing FVIII inhibitors, but benefit in those with congenital hemophilia and inhibitors has not been established and more extensive clinical studies are needed. More recently, research on reducing the incidence of inhibitor development has included mutagenizing key epitopes of the FVIII antigenic molecule to alter its immunogenicity without affecting biological activity, as well as induction of tolerance by gene therapy with immunodominant A2 and C2 domains of FVIII presented by B cells as immunoglobulin fusion proteins.

KW - Congenital hemophilia

KW - Gene therapy

KW - Immune tolerance induction (ITI)

KW - Immunosuppressive therapy

KW - Rituximab

UR - http://www.scopus.com/inward/record.url?scp=33745728702&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33745728702&partnerID=8YFLogxK

U2 - 10.1055/s-2006-946910

DO - 10.1055/s-2006-946910

M3 - Article

C2 - 16804831

AN - SCOPUS:33745728702

VL - 32

SP - 15

EP - 21

JO - Seminars in Thrombosis and Hemostasis

JF - Seminars in Thrombosis and Hemostasis

SN - 0094-6176

IS - SUPPL. 2

ER -