TY - JOUR
T1 - Patients with hemophilia A and inhibitors
T2 - prevention and evolving treatment paradigms
AU - Lillicrap, David
AU - Fijnvandraat, Karin
AU - Young, Guy
AU - Mancuso, Maria Elisa
PY - 2020/4/2
Y1 - 2020/4/2
N2 - Introduction: Novel non-replacement therapies (e.g. emicizumab) have improved the management of patients with hemophilia A with and without inhibitors while introducing new challenges and increasing the complexity of clinical decision-making. Areas covered: Use of emicizumab can substantially delay initial exposure to FVIII thereby altering the natural history of inhibitor development, but it remains unclear whether later exposure to FVIII might modify the incidence of inhibitor development. Moreover, decisions regarding initiation of immune tolerance induction (ITI) therapy in patients with newly diagnosed inhibitors have become more complicated since emicizumab was introduced. Using emicizumab in lieu of ITI has implications such as precluding the use of FVIII for breakthrough bleeds and surgery, and possibly impacting on patients’ future ability to receive gene therapy. Although bypassing agents are the mainstay of managing acute bleeds and surgery in inhibitor patients, their concomitant use with novel therapies can be difficult to manage/monitor. Evidence from the HAVEN clinical trials program suggests that minor surgeries in inhibitor patients can be performed with emicizumab alone, whereas major surgeries require the use of perioperative bypassing agents. Expert opinion: Until the long-term effects of non-replacement therapies become known, patients who develop inhibitors should continue to receive ITI.
AB - Introduction: Novel non-replacement therapies (e.g. emicizumab) have improved the management of patients with hemophilia A with and without inhibitors while introducing new challenges and increasing the complexity of clinical decision-making. Areas covered: Use of emicizumab can substantially delay initial exposure to FVIII thereby altering the natural history of inhibitor development, but it remains unclear whether later exposure to FVIII might modify the incidence of inhibitor development. Moreover, decisions regarding initiation of immune tolerance induction (ITI) therapy in patients with newly diagnosed inhibitors have become more complicated since emicizumab was introduced. Using emicizumab in lieu of ITI has implications such as precluding the use of FVIII for breakthrough bleeds and surgery, and possibly impacting on patients’ future ability to receive gene therapy. Although bypassing agents are the mainstay of managing acute bleeds and surgery in inhibitor patients, their concomitant use with novel therapies can be difficult to manage/monitor. Evidence from the HAVEN clinical trials program suggests that minor surgeries in inhibitor patients can be performed with emicizumab alone, whereas major surgeries require the use of perioperative bypassing agents. Expert opinion: Until the long-term effects of non-replacement therapies become known, patients who develop inhibitors should continue to receive ITI.
KW - bypassing agents
KW - emicizumab
KW - factor VIII
KW - fitusiran
KW - Hemophilia A
KW - inhibitors
UR - http://www.scopus.com/inward/record.url?scp=85082826517&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85082826517&partnerID=8YFLogxK
U2 - 10.1080/17474086.2020.1739518
DO - 10.1080/17474086.2020.1739518
M3 - Review article
C2 - 32186928
AN - SCOPUS:85082826517
VL - 13
SP - 313
EP - 321
JO - Expert Review of Hematology
JF - Expert Review of Hematology
SN - 1747-4086
IS - 4
ER -