Prophylaxis in children with haemophilia in an evolving treatment landscape

Abstract

Introduction For children with haemophilia, early initiation of prophylaxis is crucial to prevent life‐threatening bleeds and maintain joint health throughout life. Options for prophylaxis have recently increased from replacement therapy with standard or extended half‐life coagulation factor products to include other haemostasis products, such as the non‐replacement therapy emicizumab. Aim To review key factors that determine the choice of prophylaxis in young children. Methods Key clinical questions on the implementation of prophylaxis for haemophilia in children were identified and PubMed was searched for evidence supporting guidance on the implementation of prophylaxis. Results The results of the literature search and the practical experience of the authors were used to build consensus on when to start prophylaxis, the pros and cons of the products available to guide the choice of product, and practical aspects of starting prophylaxis to guide the choice of regimen. Conclusions In this era of increasing therapeutic choices, available information about the range of treatment options must be considered when initiating prophylaxis in young children. Parents or care givers must be sufficiently informed to allow informed shared decision making. Although plentiful data and clinical experience have been gathered on prophylaxis with clotting factor replacement therapy, its use in young children brings practical challenges, such as the need for intravenous administration. In contrast, our relatively brief experience and limited data with subcutaneously administered non‐replacement therapy (i.e., emicizumab) in this patient group imply that starting emicizumab prophylaxis in young children requires careful consideration, despite the more convenient route of administration.

Emicizumab state‐of‐the‐art update

“…Prevention is the recommended standard of care for patients with haemophilia A, aiming to prevent life‐threatening bleeds, mitigate the risk of chronic joint damage and improve quality of life 48 Emicizumab is administered subcutaneously, which makes it especially beneficial for treating paediatric populations.…”

Emicizumab for All Pediatric Patients with Severe Hemophilia A

“…45 In PWHA, it is recommended to start prophylaxis as soon as possible, ideally within the first 2 years of life and before the first joint bleed. 1,2 The frequent intravenous injections are the largest burden of prophylaxis, especially in very small children due to the requirement of a CVAD. Thus, the benefit of bleeding prevention has to be balanced against the need and risks of a CVAD implementation.…”

“…The median age of the diagnosis of severe HA is 15 months. [1][2][3] The median age of the first joint bleeding is reported to be in the range of 18 to 20 months. [1][2][3] In these patients, standard of care is a regular prophylaxis with intravenous FVIII concentrates (clotting factor concentrates [CFC]) to prevent joint damage.…”

“…start prophylaxis as soon as possible, ideally within the first 2 years of life, and before occurrence of the first joint bleeding. 1,2 Prophylaxis with CFC can be started with a full prophylaxis (three times per week, or every other day), or with a frequency of only once weekly. This schedule can then be increased to a full prophylaxis regimen, depending on the frequency of bleeding events.…”

“…However, this reduced schedule may be insufficient in younger children due to the shorter half-life, and higher physical activity, as well as injury level of children. 1 Another rare, but serious and potentially life-threatening, complication of severe HA is the intracranial hemorrhage (ICH). The incidence of ICH beyond neonatal period was reported with up to 7 per 1,000 patient-years.…”