Acquired haemophilia A (AHA) is a severe bleeding disorder caused by neutralising autoantibodies against coagulation factor VIII. The presented phase 2 study evaluated the efficacy of emicizumab, a factor VIIIa mimetic antibody, in preventing bleeding episodes in patients with AHA. The findings, recently published in The Lancet Haematology, suggest that prophylaxis with emicizumab offers an effective protection against bleeding and show that the initiation of immunosuppressive therapy can be delayed while receiving this treatment.
Acquired haemophilia A (AHA) is a severe disorder caused by neutralising autoantibodies against coagulation factor VIII, leading to severe bleeding. Standard treatment with immunosuppressive therapy is associated with adverse events and mortality, underscoring the urgent clinical need for improved therapeutic strategies in these patients. Emicizumab is a bispecific antibody that mimics the cofactor function of activated FVIII and is not affected by FVIII inhibitors because of its unique molecular structure. This study aimed to investigate the efficacy of emicizumab in the prevention of bleeding episodes and its potential to delay the initiation of immunosuppression within the initial 12 weeks post-diagnosis.
The phase 2 GTH-AHA-EMI trial enrolled adult patients with AHA from 16 haemophilia treatment centres in Germany and Austria who did not receive previous immunosuppressive therapy. A total of 47 patients received subcutaneous emicizumab (6 and 3 mg/kg on days 1 and 2, followed by 1.5 mg/kg weekly until week 12) without concurrent immunosuppression. Follow-up extended to week 24, with the primary endpoint being the number of clinically relevant bleeding episodes per patient-week until week 12. The efficacy of emicizumab was determined based on achieving a mean bleeding rate significantly below 0.15 bleeds per patient-week.
The study revealed a mean breakthrough bleeding rate of 0.04 bleeds per patient-week. In total, 33 (70%) patients did not experience any bleeding events, seven patients (15%) had one bleed, six patients (13%) had two bleeds, and one patient (2%) suffered three bleeding episodes. Adverse events of grade ≥3 included COVID-19 (n=2), acute kidney injury (n=2), and stroke (n=1). Four out of 47 patients died on study, including two deaths related to bleeding, one from COVID-19, and one from cardiac arrest. Importantly, none of these deaths were associated with the emicizumab treatment.
In conclusion, this study suggests that emicizumab prophylaxis effectively prevents bleeding in patients with AHA and that the initiation of immunosuppressive therapy can be delayed while receiving this treatment. The low number of thromboembolic events, severe infections, and fatalities observed in this study are promising.
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