Emicizumab prophylaxis in haemophilia patients older than 50 years with cardiovascular risk factors: Real‐world data

Abstract

Introduction: Emicizumab (Hemlibra™) is approved for prophylaxis of Haemophilia A (HA) patients with and without inhibitors. However, real-world data on emicizumab use in the elderly HA patients with concomitant cardiovascular risk factors are lacking. Aim: To evaluate the safety and efficacy of emicizumab in a real-world cohort of elderly HA patients. Methods: A prospective longitudinal observational study on HA patients over 50 years old treated, followed and monitored during emicizumab prophylaxis was conducted. We documented any bleeding or adverse events and collected plasma samples for emicizumab levels, aPTT and thrombin generation (TG). Results: Seventeen HA patients (2 with inhibitor), whose median age was 62.4 years (range: 51.5-77.1) composed the cohort, including 9/17 with multiple cardiovascular risk factors (high risk group). Seven patients had chronic HIV infection. The median follow-up of our cohort was 400 days (range 89-805, IQR 211-479 days). The median annualized bleeding rate (ABR) significantly decreased for all patients. Among patients who displayed significant bleeding tendencies, emicizumab steady state levels as well as TG were lower as compared with the group. The ABR of four patients concomitantly treated by antiplatelet agents was significantly higher compared with the rest of the cohort. Neither thrombosis nor thrombotic microangiopathy (TMA) was encountered. Conclusions: Emicizumab prophylaxis for HA patients older than 50 years including those with cardiovascular risk factors was well tolerated. As lower emicizumab and TG levels were observed among bleeding patients, we suggest that monitoring laboratory assays could be of value within this age group.

Emicizumab prophylaxis: Prospective longitudinal real‐world follow‐up and monitoring

“…In the very young infants, reduced levels of FIX and FX as well as increased emicizumab clearance may account for the low levels encountered 17 . Interestingly, TG of both adults was within the expected range, possibly due to the presence of cardiovascular risk factors, 23 while both children displayed extremely reduced TG. As both paediatric patients were young infants, further investigation into overall emicizumab's safety is warranted in the very young age and studies aimed at evaluating emicizumab's role in prevention of intracranial and major bleeds during infancy are underway 38 .…”

“…Unlike children, our adult patients tended to experience spontaneous target joint bleeds (Figure 1). The vicious cycle of haemorrhage‐synovitis in adult HA patients may lead to arthropathy that persists despite adequate haemostasis and is especially disabling in the ageing population 22,23 …”

“…The vicious cycle of haemorrhage-synovitis in adult HA patients may lead to arthropathy that persists despite adequate haemostasis and is especially disabling in the ageing population. 22,23 Past reports disclosed that adolescent and adult HA patients experienced thrombotic events, while concomitant BPA therapy was administered during emicizumab prophylaxis. 12,24 The second interim analysis results from the STASEY Trial described STelevation myocardial infarction due to coronary artery thrombosis in a 55-year-old patient who was treated by emicizumab alone, yet the event was considered unrelated to his prophylaxis.…”

Real-World Data on Bleeding Patterns of Hemophilia A Patients Treated with Emicizumab

“…Interestingly, all of the spontaneous joint bleeds of our patients occurred into target joints, which are defined as joints experiencing hemarthroses threeor moretimes in a period of 6 months [ 18 ] due to the vicious cycle of hemorrhage–synovitis. That vicious cycle in adult HA patients may lead to arthropathy that persists despite adequate hemostasis, and it is especially disabling in the aging population [ 15 , 20 ]. The pooled analysis of the HAVEN studies showed that a large proportion of patients did not bleed into previously existing target joints, and that some “lost” their target joint definition due to reduced ABR.…”

“…In their pooled analyses of HAVEN 1–4 studies, Callaghan et al [ 12 ] demonstrated an increase in the percentage of patients with zero treated bleeds throughout the study period (from 70.8% in weeks 1–24 to 83.7% in weeks 73–96). Real-world data that addressed the reduction in the annual bleeding rate (ABR) among emicizumab-treated patients are available [ 13 , 14 , 15 ], but comparable data on bleeding patterns during emicizumab therapy (specifically, spontaneous vs. traumatic, location of the bleed, and requirement of additional hemostatic therapy) are scarce. Moreover, there are none on the incidence of bleeding among HA patients during different time periods starting from the initiation of emicizumab therapy and continuing over time.…”