Factor VIII inhibitors in hemophilia A treated with emicizumab: longitudinal follow-up of outcomes

Levy-Mendelovich, Sarina; Atia, Nitzan; Budnik, Ivan; Barg, Assaf Arie; Avishai, Einat; Cohen, Omri; Brutman-Barazani, Tami; Livnat, Tami; Kenet, Gili

doi:10.1016/j.rpth.2023.100278

Cited by 2 publications

(3 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The observed decrease in inhibitor levels following the initiation of emicizumab is consistent with previous reports and stems from lack of exposure to FVIII. 28 This phenomenon highlights the potential for a 'therapeutic window' allowing for a 'a short-term on-demand FVIII administration for breakthrough bleeds or surgical interventions in emicizumab treated patients with historical FVIII inhibitors.…”

Section: Discussionmentioning

confidence: 98%

Emicizumab prophylaxis in infants: Single‐centre experience

Levy‐Mendelovich,

Greenberg‐kushnir,

Budnik

et al. 2024

Br J Haematol

Self Cite

View full text Add to dashboard Cite

SummaryThe hallmark of haemophilia A (HA) therapy is prophylaxis, aimed at spontaneous bleeding prevention. Emicizumab provides a viable alternative to intravenous factor replacement therapy. However, data on its use in infants are limited. This single‐centre open arm prospective study reports on emicizumab prophylaxis in infants. We included severe HA patients under 1 year who started emicizumab prophylaxis since 2018, with longitudinal follow‐up. The study collected data on demographics, clinical and laboratory variables, the occurrence of bleeding events, surgeries and treatment outcomes. Of the 27 enrolled infants, whose median age at prophylaxis initiation was 7 months, 24 primarily choose to start emicizumab therapy (3/27 switched from FVIII prophylaxis due to development of FVIII inhibitors). The median age for prophylaxis initiation decreased to 3 months in 2023. Following emicizumab initiation, the median calculated ABR decreased, and no intracranial haemorrhages were observed. Thrombin generation showed a significant improvement in peak height and endogenous thrombin potential at steady state after a loading period. Our study highlights a shift towards early prophylaxis in the era of non‐replacement therapies. It underscores the need for continuous evaluation and refinement of treatment approaches, emphasizing personalized care and diligent monitoring in the evolving field of paediatric haemophilia care.

show abstract

Section: Discussionmentioning

confidence: 98%

Emicizumab prophylaxis in infants: Single‐centre experience

Levy‐Mendelovich,

Greenberg‐kushnir,

Budnik

et al. 2024

Br J Haematol

Self Cite

View full text Add to dashboard Cite

show abstract

“…Levy‐Mendelovich et al. recently reported their national experience in treating 51 PWHAI on emicizumab 45 . The majority had undergone ITI and reached a defined endpoint (failure, partial tolerance, successful tolerance).…”

Section: Discussionmentioning

confidence: 99%

“…Four patients with LTIs (< 2 BU/mL) received 1−2 doses of FVIII around minor procedures, and no rise in inhibitor titer was seen. Eight of 15 successfully tolerized PWHAI received FVIII for breakthrough bleeds without an effect on inhibitor titer 45 . These examples illuminate some of the unknowns in this landscape, including how to predict if the inhibitor titer will fall to low or undetectable levels in the absence of FVIII, and thus, preserve the potential to use FVIII for life‐threatening bleeds or, as suggested here, can more PWHAI be treated intermittently with FVIII for bleeding events with transient to no increase in titer after 1−2 EDs?…”

Section: Discussionmentioning

confidence: 99%

Haemophilia in the era of novel therapies: Where do inhibitors feature in the new landscape?

Meeks,

Zimowski

2024

Haemophilia

View full text Add to dashboard Cite

IntroductionThe advent of therapeutic recombinant factor VIII (FVIII) and factor IX (FIX) protein infusions revolutionized the care of persons with haemophilia in the 1990s. It kicked off an era with the increasing use of prophylactic factor infusions for patients and transformed conversations around the ideal trough activity levels as well as the ultimate goals in tailored, individualized care. Our knowledge surrounding the immunologic basis of inhibitor development and treatment derives from a time when patients were receiving frequent factor infusions and focused on immune tolerance induction following inhibitor development.DiscussionMore recently, care was revolutionized again in haemophilia A with the approval of emicizumab, a bispecific antibody mimicking activated FVIII function, to prevent bleeding. The use of emicizumab prophylaxis has resulted in a significantly slower accumulation of factor exposure days and continued effective prophylaxis in the case of inhibitor development. While emicizumab is effective at reducing the frequency of bleeding events in patients with haemophilia A, management of breakthrough bleeds, trauma, and surgeries still requires additional treatment. Ensuring that FVIII is a therapeutic option, particularly for life‐threatening bleeding events and major surgeries is critical to optimizing the care of persons with haemophilia A. Other novel non‐factor concentrate therapies, including rebalancing agents, will dramatically change the landscape for persons with haemophilia B with inhibitors.ConclusionThis review discusses the changing landscape regarding the timing of inhibitor development and management strategies after inhibitor development, stressing the importance of education across the community to continue to vigilantly monitor for inhibitors and be prepared to treat persons with inhibitors.

show abstract

Factor VIII inhibitors in hemophilia A treated with emicizumab: longitudinal follow-up of outcomes

Cited by 2 publications

References 35 publications

Emicizumab prophylaxis in infants: Single‐centre experience

Emicizumab prophylaxis in infants: Single‐centre experience

Haemophilia in the era of novel therapies: Where do inhibitors feature in the new landscape?

Contact Info

Product

Resources

About