Key questions in the new hemophilia era: update on concomitant use of FVIII and emicizumab in hemophilia A patients with inhibitors

ABSTRACT

Introduction: Immune tolerance induction (ITI) is the primary therapeutic strategy and only proven method to eradicate inhibitors to coagulation factor VIII (FVIII) in hemophilia A. Emicizumab, a humanized bispecific monoclonal antibody that mimics the function of activated FVIII, has expanded options to treat hemophilia A. The availability of emicizumab necessitates a revisit of recommendations for managing patients with inhibitors.

Areas covered: Current evidence is reviewed about the concomitant use of emicizumab and FVIII concentrates during and after ITI. Areas where data are lacking are highlighted and ongoing studies designed to address these issues are described.

Expert opinion: Inhibitor eradication remains a desirable goal. All patients with inhibitors should be offered at least one attempt at ITI. Emicizumab monotherapy is an option for inhibitor patients who are not candidates for ITI. Evidence is emerging about the use of emicizumab during ITI to prevent bleeds. Studies are currently addressing the safety, efficacy, and feasibility of concomitant emicizumab and FVIII in ITI. As evidence regarding the risk of inhibitor recurrence and need for continued FVIII to maintain immune tolerance post-ITI is limited, the role of emicizumab alone or in combination with FVIII after ITI is the subject of an upcoming study.

KEYWORDS:

• Hemophilia A
• inhibitor
• immune tolerance induction
• FVIII
• emicizumab

Article highlights

• Eradication of inhibitors to coagulation factor VIII (FVIII) remains a desirable goal. All patients with hemophilia A and inhibitors should be offered at least one attempt at immune tolerance induction (ITI). Emicizumab monotherapy is an option for inhibitor patients who must delay or are unable/unwilling to undergo ITI or those who fail ITI.

• Evidence is emerging about the use of emicizumab to prevent bleeds during ITI. Results of ongoing studies are expected to answer unresolved questions about the safety, efficacy, and feasibility of concomitant emicizumab and FVIII in ITI.

• Evidence about the risk of inhibitor recurrence after successful ITI and the need for continued FVIII to maintain immune tolerance post-ITI is limited. The potential role of emicizumab alone or in combination with FVIII post-ITI is to be evaluated in the upcoming PRIORITY (PReventing InhibitOR Recurrence IndefiniTelY) study.

Acknowledgments

Editorial assistance was provided by Robert Furlong and Kerry Dechant on behalf of Content Ed Net (Madrid, Spain) with funding from Grifols (Barcelona Spain).

Declaration of interest

M Carcao has received research support from Bayer, CSL-Behring, Novo Nordisk, Octapharma, Pfizer, Sanofi, and Shire/Takeda; and honoraria from Bayer, Biotest, CSL Behring, Grifols, Novo Nordisk, Octapharma, Pfizer, Roche, Sanofi, Sobi, and Shire/Takeda.

ME Mancuso has received honoraria/consultation and speaker fees from Bayer, Biomarin, CSL Behring, Catalyst, Grifols, Kedrion, Novo Nordisk, Octapharma, Pfizer, Roche, Sobi and Takeda.

G Young has received research support from Genentech, Grifols, Takeda; is a consultant for Genentech/Roche, Novo Nordisk, Sanofi Genzyme, and UniQure; has received honoraria from BioMarin, Genentech/Roche, Freeline, Grifols, Novo Nordisk, Sanofi Genzyme, Spark, Takeda, and UniQure; and is on Scientific Advisory Boards for BioMarin, Genentech/Roche, Freeline, Grifols, Novo Nordisk, Sanofi Genzyme, Spark, Takeda, and UniQure.

V Jimenez-Yuste has received grants/research support from Bayer, Grifols, Novo Nordisk, Octapharma, Pfizer, Roche, Sobi, and Takeda; and has received honoraria or consultation fees from Bayer, CSL Behring, Grifols, NovoNordisk, Octapharma Pfizer, Roche, Sobi, and Takeda.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This review is based on presentations from a Grifols-sponsored symposium at the International Society on Thrombosis and Haemostasis 2020 Virtual Congress. The paper is otherwise not funded.