Dilemmas on emicizumab in children with haemophilia A: A survey of strategies from PedNet centres

Abstract

IntroductionHaemophilia A care has changed with the introduction of emicizumab. Experience on the youngest children is still scarce and clinical practice varies between haemophilia treatment centres.AimWe aimed to assess the current clinical practice on emicizumab prophylaxis within PedNet, a collaborative research platform for paediatricians treating children with haemophilia.MethodsAn electronic survey was sent to all PedNet members (n = 32) between October 2022 and February 2023. The survey included questions on the availability of emicizumab, on the practice of initiating prophylaxis in previously untreated or minimally treated patients (PUPs or MTPs) and emicizumab use in patients with or without inhibitors.ResultsAll but four centres (28/32; 88%) responded. Emicizumab was available in clinical practice in 25/28 centres (89%), and in 3/28 for selected patients only (e.g. with inhibitors). Emicizumab was the preferred choice for prophylaxis in PUPs or MTPs in 20/25 centres; most (85%) started emicizumab prophylaxis before 1 year of age (30% before 6 months of age) and without concomitant FVIII (16/20; 80%). After the loading dose, 13/28 centres administered the recommended dosing, while the others adjusted the interval of injections to give whole vials. In inhibitor patients, the use of emicizumab during ITI was common, with low‐dose ITI being the preferred protocol.ConclusionMost centres choose to initiate prophylaxis with emicizumab before 12 months of age and without concomitant FVIII. In inhibitor patients, ITI is mostly given in addition to emicizumab, but there was no common practice on how to proceed after successful ITI.

Haemophilia in the era of novel therapies: Where do inhibitors feature in the new landscape?

“…For those individuals with HTIs, the current treatment plan typically consists of emicizumab prophylaxis for bleeding prevention with or without ITI for inhibitor eradication. In 2019 the Atlanta Protocol reported the feasibility of concomitant use of emicizumab with ITI at 50−100 IU/kg three times per week, and in a recent survey of PedNet centers the majority of centers using emicizumab during ITI typically chose a similar low dose ITI regimen 43,44 . The combination of emicizumab with low dose ITI takes advantage of the haemostatic efficacy of emicizumab prophylaxis while minimizing the cost and treatment burden of ITI and potentially avoiding CVAD placement.…”

Single centre experience of the use of emicizumab in previously untreated and minimally treated patients under 18 months of age

“…In the studied cohort, the median age for initiating emicizumab prophylaxis was 8.2 months, and all patients received weight‐adjusted maintenance dose of 3 mg/kg administered fortnightly. A recent survey 19 conducted internationally across several paediatric haemophilia‐treating centres found that 85% of centres initiated emicizumab prophylaxis before the age of 12 months, with the majority starting between 6 and 12 months. This survey also revealed the wide variation in clinical practice regarding dosing.…”

Bleeding control improves after switching to emicizumab: Real‐world experience of 177 children in the PedNet registry

“…Inhibitors were defined as ≥2 consecutive positive inhibitor tests with reduced recovery. 18 As many centres start FVIII prophylaxis with once weekly infusions, the start of prophylaxis was defined as infusion of CFCs at regular intervals, in the absence of bleeding, at least three times within 15 days for at least two consecutive months. 19 In inhibitor patients, ITI was defined as any regular FVIII infusion schedule given ≥3x/week and at a dose ≥45 IU/kg/infusion for ≥4 weeks.…”

“…Testing for ADAs against emicizumab was done indirectly (by APTT and/or emicizumab levels) in most centers. 18 During emicizumab prophylaxis, FVIII inhibitor testing was performed at least annually or after exposure to FVIII. Patients were receiving emicizumab dosing according to the label (i.e., 6 mg/kg/4wks, with varying intervals).…”