Real-World Experience Using Emicizumab Prophylaxis for Hemophilia a: Single-Center Experience

Abstract

INTRODUCTION: Emicizumab is a recombinant humanized bispecific antibody that mimics Factor VIII by bridging Factor IXa and X. It is an important breakthrough in the therapeutic armamentarium for Hemophilia A. Recently concluded Phase III HAVEN trials demonstrated that prophylaxis with emicizumab is superior to recombinant Factor VIII (rFVIII). Patients with Hemophilia A with inhibitors had a 79% reduction in the Annualized Bleeding Rate (ABR) while on emicizumab prophylaxis vs other bypassing agents. Patients without inhibitors had a 68% reduction in ABR on emicizumab vs rFVIII prophylaxis. However, there is limited data on its use in the post-marketing era. METHODS: We report our experience with emicizumab in children and adults with Hemophilia A with and without inhibitors at a single Hemophilia Treatment Center. This Northwell IRB approved retrospective analysis (Jan 2017 - Jun 2020) included data from 12 months prior to starting emicizumab prophylaxis RESULTS: A total of 38 patients on emicizumab prophylaxis were included. 35 patients (92.1%) had severe and 3 (7.9%) had moderate Hemophilia A. 11 patients (28.9%) had a FVIII inhibitor. The mean age was 16.4 yrs with 18 patients (47%) below the age of 12 (age limit used in HAVEN trials). 54.1% of patients were Caucasian, 18.9% were Asian and 16.2% were African American. Thirty patients (78.9%) were on prophylaxis with either rFVIII (71.5%) or FEIBA (21.4%) before starting emicizumab. All 38 patients were started on emicizumab with a loading dose of 3 mg/kg once weekly for 4 weeks followed by a maintenance dose of 1.5 mg/kg weekly. The ABR decreased by 52% for inhibitor patients (3.6 events before and 1.7 events after starting emicizumab). Similarly, there was a dramatic 70.6% reduction for non-inhibitor patients (1.5 events before and 0.44 events after starting emicizumab). Patients on emicizumab prophylaxis experienced 35 bleeding events over 24 months. Nine out of these 35 events occurred in one patient alone with a high titer FVIII inhibitor. 56.5% of these events were joint bleeds, 26.1% (muscle bleeds), 13% (soft tissue bleeds) and 4.4% were mucocutaneous bleeds. Barring 2 events, all episodes (93.9%) were managed outpatient. A majority of these bleeds (72.1%) in inhibitor patients were treated with recombinant Factor VIIa (rVIIa, 16-24 doses for documented hemarthroses) and 3.4% were treated with FEIBA after nonresponse to rVIIa (9-15 doses) due to delayed treatment. Remaining non -inhibitor patients were treated with rFVIII (2-5 doses) with a good response. 52 % of these bleeds were trauma-related. Five surgeries were conducted in the inhibitor patients while on emicizumab prophylaxis and none experienced perioperative bleeding. RVIIa was used as a bypassing agent for 2 of these surgeries - a hemispherectomy and a port removal. No bypassing agent was used for the remaining 3 port removals. Five surgeries (1 total knee arthroplasty and 4 port removals) were performed in patients without a FVIII inhibitor. Recombinant Factor VIII was used as the replacement agent and the patient with knee arthroplasty experienced post-operative bleeding. There were no thrombotic episodes or deaths and all but one continued on emicizumab. The patient post knee arthroplasty discontinued emicizumab after recurrent bleeds into the replaced joint despite aggressive replacement with rFVIII and absence of an inhibitor. DISCUSSION: We report a real-world experience on the use of emicizumab prophylaxis for Hemophilia A with and without inhibitors in children and adults with 78.9% of our cohort below the age of 21 years. Our study demonstrated a similar decrease in ABR for non-inhibitor patients comparable to the HAVEN clinical trials. However, our inhibitor patients experienced a lower bleed reduction rate on emicizumab and all patients still experienced a considerable number of trauma-related bleeds (likely due to increased participation of inhibitor patients in sports). Two patients with traumatic muscle/joint bleeds were treated with aPCC due to non-response to rVIIa suggesting the need for early treatment of suspected bleeds on emicizumab. No thrombotic events or thrombotic microangiopathy was observed in our patient cohort. Our data suggest the need for ongoing patient education for early bleed recognition on emicizumab prophylaxis, prompt treatment of breakthrough bleeds and pre-sports prophylaxis with FVIII or bypassing agents. Disclosures Acharya: BPL: Membership on an entity's Board of Directors or advisory committees; Novonordisk: Membership on an entity's Board of Directors or advisory committees; Bayer Pharma Inc.: Research Funding.