Management of haemophilia A with inhibitors: A regional cross‐talk

Abstract

Introduction The development of inhibitors with factor VIII (FVIII) replacement therapy is one of the most common and challenging complications of haemophilia A (HA) treatment, jeopardising treatment efficacy and predisposing patients to high risks of morbidity and mortality. The management of patients with inhibitors is particularly challenging in countries where resources are limited. Aim To provide a comprehensive summary of the management of HA with inhibitors while focusing on differences in practice between Western and non‐Western countries and how resource scarcity can impact HA management, leading to suboptimal outcomes in patients with inhibitors. Methods Summary of key evidence and regional expert opinion. Results We address, particularly, the diagnosis of and testing for inhibitors, as well as the epidemiology of inhibitors, including incidence, prevalence and disease burden. Secondly, we provide an overview of the current treatment landscape in HA with inhibitors regarding the eradication of inhibitors with immune tolerance induction and the treatment and prevention of bleeding with bypassing agents, non‐factor replacement agents and other experimental therapies. This is complemented with insights from the authors around the applicability of, and challenges associated with, such therapies in their settings of practice. Conclusions We conclude by proposing some key steps towards bridging the gaps in the management of HA with inhibitors in resource‐limited countries, including: (1) the collection of quality data that can inform healthcare reforms and policies; (2) improving disease knowledge among healthcare practitioners and patients with the aim of standardising disease management across centres and (3) working towards promoting equal access to HA care and therapies for everyone.

FVIII inhibitor surveillance in children with hemophilia A in Indonesia: a report from the Indonesian Pediatric Hematology-Oncology Working Group

“…However, the COVID-19 pandemic and difficult access to transportation resulted in a low number of patients participating in our study. The prevalence of FVIII inhibitors among patients with severe HA in our study (25/219, 12%) was considered relatively low compared to that in studies from Western countries conducted by the Research of Determinants of Inhibitor Development (PedNet study group) and the UK Hemophilia Centre Doctors' Organization (UKHCDO), with the most reported prevalence ranging between 20% and 30% of severe HA [9][10][11][12]. This result may be owing to the use of low-dose FVIII plasma-derived therapy in Indonesia.…”

“…In India, one study on patients with bleeding disorders also reported a slightly lower prevalence of inhibitors, which occurred in 6.1% of 1,285 patients with HA. This small number also reflects the undertreatment of patients with hemophilia, where only infrequent episodic treatment is applied, thus rarely resulting in peak treatment moments that subsequently lead to inhibitor development, especially in young patients [10].…”

“…Muscle and joint bleeding are the main clinical presentations of severe hemophilia, and their burden is greater in patients with inhibitors than in those without [ 2 , 10 ]. Some factors, including patient compliance, referral problems to hemophilia centers, and large-scale social restrictions during the COVID-19 pandemic in some provinces, affected the data collection in this study.…”

Budget impact and cost-utility analysis of prophylactic emicizumab versus on-demand bypassing agents for adolescent severe haemophilia A patients with inhibitors in India

“…This means that the patients on emicizumab prophylaxis gain additional QALYs and it costs the health system lesser than the existing on-demand bypassing agent treatment (i.e., less costly and more effective). Severe Haemophilia A patients with inhibitors are currently treated with on-demand bypassing agents (recombinant factor VIIa/APCC) across various public health hospitals of India [ 23 ]. Prophylactic emicizumab therapy, in addition to being a cost-saving intervention, has several other advantages such as prevention or reduction in the number of bleeding episodes, ease of compliance (given the once or twice monthly prophylactic regimen), reduction in healthcare system costs (subcutaneous administration of agent) and better quality of life for the patients [ 24 ].…”

The self-reactive FVIII T cell repertoire in healthy individuals relies on a short set of epitopes and public clonotypes

“…Although new hemostatic agents, bypassing the need for FVIII replacement, are now available, spontaneous bleeds may still occur in individuals under prophylaxis non-FVIII therapies, leading to the need for FVIII injections ( 3 , 4 ). However, the development of neutralizing anti-FVIII antibodies, known as “inhibitors”, can complicate or preclude effective FVIII replacement therapy ( 5 ). The immunological mechanisms behind the immunogenicity of pro-coagulant FVIII remain unclear ( 6 ).…”