Emicizumab initiation and bleeding outcomes in people with hemophilia A with and without inhibitors: A single‐center report

Abstract

Background Emicizumab, a bispecific antibody factor VIII mimetic, is approved for prophylaxis in hemophilia, and has different risks and side effects compared to factor VIII products. Objective To better understand the early impact of emicizumab on our patients at the University of Colorado Hemophilia and Thrombosis Center (UCHTC), we evaluated adverse reactions, factor prophylaxis overlap, and bleeding rates after starting emicizumab through a quality improvement project. Patients/Methods A retrospective chart review and structured phone interview were conducted from June to September 2019 for all patients who had started emicizumab at the UCHTC. Data about emicizumab dosing, reactions, bleeding events, and bleeding treatment were collected in 68 children and adults (aged 0.55‐79.8 years, on emicizumab a median 213 days; range, 51‐1229 days) with hemophilia A (35.3% with past or current inhibitor). Results Adverse reactions were primarily skin reactions, with no anaphylactic reactions or thrombosis. Bleeding events, defined as pain or swelling treated with factor or supportive measures, demonstrated wide variability, with 25 of 68 experiencing zero bleeds and 5 of 68 experiencing >8 bleeds per year. The most prevalent bleed type was traumatic musculoskeletal bleeding. Bleeding events occurred more often in the first 10 weeks after starting emicizumab, but no time period was without bleeding events. The majority of patients were prescribed every‐week or every‐2‐week dosing, but some had alternative dosing frequency. Conclusions Real‐world emicizumab use in our center was characterized by variations in prescribing practices and bleeding outcomes and lack of severe adverse reactions.

Emicizumab state‐of‐the‐art update

“…Beyond the clinical trials, emicizumab safety has been documented in multiple real‐world experiences in patients with and without inhibitors 13–19 . In these studies, the emicizumab safety profile was similar to that seen in clinical trials.…”

“…Yet, paediatric data and data regarding emicizumab's potential use in PUPs were not specified. 13 The most extensive prospective paediatric study reported to date is the Israeli cohort that sought to evaluate safety, efficacy, and laboratory monitoring of emicizumab prophylaxis in a cohort of 40 children with severe HA, including 22 non-inhibitor patients and nine infants younger than one year. Bleeding, trauma, adverse events, and surgeries were documented during a median follow-up of 45 weeks.…”

“…Sixteen surgical interventions were performed in 12 patients, with no thrombotic complications or thrombotic microangiopathy. Elevation in the thrombin generation was observed following emicizumab prophylaxis, with lower values recorded in younger infants, yet as all bleedings were trauma‐related, laboratory monitoring could not predict bleeding risk 13 . Further longitudinal follow–up of the mixed Israeli cohort (107 patients with severe HA, including 58 children whose median (IQR) age was 6 1–11 years), followed for a median of 67 weeks (up to 144 weeks) disclosed zero bleeds in half of the patients.…”

“…Elevation in the thrombin generation was observed following emicizumab prophylaxis, with lower values recorded in younger infants, yet as all bleedings were trauma-related, laboratory monitoring could not predict bleeding risk. 13 Further longitudinal follow-up of the mixed Israeli cohort (107 patients with severe HA, including 58 children whose median (IQR) age was 6 1-11 years), followed for a median of 67 weeks 54 Emicizumab prophylaxis is becoming the standard of care for paediatric patients with HA and inhibitors. Using emicizumab in place of ITI has been described in paediatric patients.…”

The bleeding phenotype in people with nonsevere hemophilia

“…The ABR reported in our cohort is comparable to the ABR of previous study populations on emicizumab. 22,23 …”