TY - JOUR
T1 - Inhibitors in haemophilia A and B
T2 - Management of bleeds, inhibitor eradication and strategies for difficult-to-treat patients
AU - Ljung, Rolf
AU - Auerswald, Guenter
AU - Benson, Gary
AU - Dolan, Gerry
AU - Duffy, Anne
AU - Hermans, Cedric
AU - Jiménez-Yuste, Victor
AU - Lambert, Thierry
AU - Morfini, Massimo
AU - Zupančić-Šalek, Silva
AU - Santagostino, Elena
PY - 2019
Y1 - 2019
N2 - The standard therapy for patients with haemophilia is prophylactic treatment with replacement factor VIII (FVIII) or factor IX (FIX). Patients who develop inhibitors against FVIII/FIX face an increased risk of bleeding, and the likelihood of early development of progressive arthropathy, alongside higher treatment-related costs. Bypassing agents can be used to prevent and control bleeding, as well as the recently licensed prophylaxis, emicizumab, but their efficacy is less predictable than that of factor replacement therapy. Antibody eradication, by way of immune tolerance induction (ITI), is still the preferred management strategy for treating patients with inhibitors. This approach is successful in most patients, but some are difficult to tolerise and/or are unresponsive to ITI, and they represent the most complicated patients to treat. However, there are limited clinical data and guidelines available to help guide physicians in formulating the next treatment steps in these patients. This review summarises currently available treatment options for patients with inhibitors, focussing on ITI regimens and those ITI strategies that may be used in difficult-to-treat patients. Some alternative, non-ITI approaches for inhibitor management, are also proposed.
AB - The standard therapy for patients with haemophilia is prophylactic treatment with replacement factor VIII (FVIII) or factor IX (FIX). Patients who develop inhibitors against FVIII/FIX face an increased risk of bleeding, and the likelihood of early development of progressive arthropathy, alongside higher treatment-related costs. Bypassing agents can be used to prevent and control bleeding, as well as the recently licensed prophylaxis, emicizumab, but their efficacy is less predictable than that of factor replacement therapy. Antibody eradication, by way of immune tolerance induction (ITI), is still the preferred management strategy for treating patients with inhibitors. This approach is successful in most patients, but some are difficult to tolerise and/or are unresponsive to ITI, and they represent the most complicated patients to treat. However, there are limited clinical data and guidelines available to help guide physicians in formulating the next treatment steps in these patients. This review summarises currently available treatment options for patients with inhibitors, focussing on ITI regimens and those ITI strategies that may be used in difficult-to-treat patients. Some alternative, non-ITI approaches for inhibitor management, are also proposed.
KW - coagulation disorders
KW - paediatric haematology
KW - quality of life
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U2 - 10.1111/ejh.13193
DO - 10.1111/ejh.13193
M3 - Article
AN - SCOPUS:85057991589
VL - 102
SP - 111
EP - 122
JO - European Journal of Haematology
JF - European Journal of Haematology
SN - 0902-4441
IS - 2
ER -