PB1265 - Switching prophylaxis during an immune tolerance induction evolving with failure: a case report from a Brazilian Hemophilia Treatment Center

Background: Factor VIII (FVIII) prophylaxis is recommended to prevent bleeds in people with hemophilia A (PwHA). However, up to 30% of severe PwHA (residual plasmatic FVIII activity < 1%) develop anti-FVIII (FVIII) neutralizing antibodies (i.e., inhibitors), leading to ineffectiveness of FVIII replacement and worse outcomes. Immune tolerance induction (ITI) is the treatment of choice to eradicate inhibitors, but it demands frequent intravenous infusions and a higher risk of bleeding. Bypassing agent (BpA) prophylaxis was recommended to avoid bleeding during ITI. Emicizumab is currently available as a prophylactic agent for PwHA and inhibitors, although its impact during ITI is not well described.

Aims: We reported the effect of changing the prophylactic agent during ITI in a child treated at a Brazilian Hemophilia Treatment Center.

Methods: Data were collected from the medical files.

Results: The male child was diagnosed with severe hemophilia A (non-identified mutation) at 1.3 year, starting primary prophylaxis with standard half-life recombinant FVIII soon after. A high-titer inhibitor was detected at 1.5 year and ITI was started within 0.2 year (50IU/kg, 3x/week) after 1 treated bleed. Both historic inhibitor peak and inhibitor titer immediately before ITI start were 4.9BU/mL. During ITI, inhibitor titers continuously rose to 104BU/mL, associated with 6 treated bleeds, despite regimen increment to 100IU/kg daily and BpA prophylaxis. BpA prophylaxis was switched to emicizumab prophylaxis at 0.9 year of ITI. Two bleeds were treated during emicizumab loading. No treated bleeds were reported after that. Inhibitor titers continuously decreased, and ITI was withdrawn after 2.8 of treatment (partial success due to abnormal FVIII pharmacokinetics). Emicizumab prophylaxis was maintained, and no treated bleeds were reported after 6 months of ITI withdrawal.

Conclusion(s): Switching to emicizumab prophylaxis was associated with ITI partial success in a predefined good-outcome risk child with hemophilia A and inhibitor evolving with ITI failure.