Transition of Hemophilia A Patients with a History of Coagulation Factor Inhibitor to Emicizumab
During the World Federation of Hemophilia (WFH) conference, held virtually in June 2020, interesting results were presented for patients with Hemophilia A who had a history of FVIII inhibitor and are now using Emicizumab.
Introduction
The standard of care for patients with Hemophilia A (HA) and an inhibitor (neutralizing antibodies) of coagulation factor is currently immune tolerance induction (ITI). After successfully achieving tolerance, patients typically remain on prophylaxis with factor VIII concentrate (FVIII), maintaining long-term exposure to exogenous FVIII, which may contribute to sustaining a favorable immune response. The question remains what transitioning to Emicizumab and using FVIII concentrate only in case of bleeding or major surgery means for these patients.
Experience and Results from One Center
Researchers from Atlanta evaluated data from 8 patients with HA and a history of high-titer inhibitor (range 1.7–819 BU/ml). Successful immune tolerance was achieved in 3 patients through ITI, while 5 achieved only partial tolerance. Six patients transitioned to Emicizumab monotherapy, with 2 combining Emicizumab with intermittent FVIII administration.
In the Emicizumab monotherapy group, after 5 months of treatment, an inhibitor was detected at a low titer (2.5 BU/ml) in 1 patient. Interestingly, anti-FVIII IgG4 antibodies were detected in 3 out of 5 patients who were on sole Emicizumab and tested negative for the inhibitor.
Both patients receiving Emicizumab combined with FVIII initiated treatment with only partial tolerance and negative inhibitor tests but were positive for anti-FVIII IgG4 antibodies. No anti-FVIII IgG1 antibodies were detectable in any patient.
Conclusion and Discussion
Based on this observation of a small patient sample, it can be concluded that for the majority of HA patients with a history of inhibitor who underwent ITI before Emicizumab treatment, the inhibitor remained undetectable during Emicizumab therapy. However, the presence of anti-FVIII IgG4 antibodies might indicate that intense exposure to FVIII concentrates during severe bleeding or major surgery might provoke an anamnestic antibody response. Nevertheless, this experience is valuable as Emicizumab has introduced significant and revolutionary advancements in Hemophilia A treatment, naturally leading to questions regarding the management of ongoing care.
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Source: Batsuli G., Green A., Meeks S. L., Sidonio R. F. jr. Inhibitor status of patients with hemophilia A who transition to Emicizumab after immune tolerance induction. Abstracts of the World Federation of Hemophilia, Virtual Summit – Connecting the Global Bleeding Disorders Community, June 2020. Haemophilia 2020 Jun 1; 26 (S4): MED-FP-011 (139).
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