Introduction Treatment of hemophilia A in Brazil is offered to all patients at no cost. However, several unmet medical needs exist. Method In this study, we applied the Delphi method to discuss with seven hemophilia A specialists the challenges that patients and the health system face regarding hemophilia A treatment and opportunities for improvement. Results A consensus was obtained regarding the number of weekly infusions and patient adherence to treatment. The bleeding profile, unfavourable pharmacokinetics (PKs), low adherence and high daily activity were patient profiles that would benefit from using the extended half-life (EHL) recombinant factor VIII (rFVIII). The advantages of treatment with the EHL rFVIII were the lower number of infusions per week, which could increase patient adherence and decrease the risk of bleeds, due to a more constant plasma level, a lower value. Additionally, the EHL rFVIII could improve quality of life, especially in patients with high daily activity, such as adolescents and young adults. The panelists mentioned that EHL rFVIII, if available, could be offered first to the priority group (adolescents between 12 and 19 years old), followed by adults (20 to 64 years old) and elderly people (over 65 years old). Conclusion In summary, the EHL rFVIII offers the optimal prophylaxis by decreasing the dose frequency, increasing the treatment adherence and improving the QoL, without compromising safety and efficacy. cost However exist study improvement profile PKs, PKs , (PKs) halflife half life (EHL rFVIII. . (rFVIII) week bleeds level value Additionally available 1 old, old 20 (2 6 over old. summary frequency QoL efficacy (PKs (rFVIII 2 (

RESUMO Objetivo: Descrever o uso da viscossuplementação com ácido hialurônico em pacientes com artropatia hemofílica (HA), sua eficácia na dor, a funcionalidade do membro e a qualidade de vida após sua aplicação. Métodos: Revisão sistemática da literatura (RSL) que seguiu as diretrizes PRISMA, sem limitação de idioma ou ano de publicação. A pesquisa foi realizada em abril de 2020 nas seguintes bases de dados médicas: PubMed, Cochrane Library, EMBASE, BVS/BIREME, Scopus, Web of Science, EBSCOhost e ProQuest. A estratégia de pesquisa foi: (hemofilia AND joint disease) OR (artropatia hemofílica OU artropatia hemofílica) E viscossuplementação. Resultados: A RSL identificou 127 artigos, dos quais 10 foram selecionados para extração de dados e análise qualitativa. Os 10 artigos selecionados incluíram 297 articulações com AH em 177 indivíduos hemofílicos. Nossa revisão mostrou resultados positivos na melhora da dor, na capacidade funcional e na qualidade de vida. Não foram observados efeitos adversos importantes. Conclusão: A evidência científica atual a respeito da viscossuplementação com ácido hialurônico é escassa, mas os resultados apresentados nesta pesquisa sugerem que é uma opção terapêutica eficaz e segura para diminuir a dor e melhorar a capacidade funcional em pacientes com AH. Nível de Evidência II, Revisão Sistemática. Objetivo HA, HA , (HA) aplicação Métodos (RSL PRISMA publicação 202 médicas PubMed Library EMBASE BVSBIREME BVS BIREME BVS/BIREME Scopus Science ProQuest hemofilia disease Resultados 12 1 qualitativa 29 17 hemofílicos importantes Conclusão escassa II Sistemática (HA 20 2

ABSTRACT Objective: To describe the efficacy of using viscosupplementation in patients with hemophilic arthropathy (HA), on pain, limb functionality, and quality of life. Methods: A systematic review of the literature was performed following the PRISMA guidelines without limitations of language or year of publication. The search was performed on the following medical databases: PubMed, Cochrane Library, EMBASE, BVS/BIREME, Scopus, Web of Science, EBSCOhost, and PROQUEST in April 2020. The search used the following word: (hemophilia AND joint diseases) OR (haemophilic arthropathy OR hemophilic arthropathy) AND viscosupplementation. Results: The systematic review identified 127 articles, 10 of which were selected for data extraction and qualitative analysis. The 10 selected articles included 297 joints with HA in 177 hemophilic subjects. Our review showed positive results in alleviating pain and improving functional capacity, and quality of life. No major adverse effects were observed. Conclusion: There is a lack of scientific evidence regarding viscosupplementation with hyaluronic acid, but the results presented in this research suggest that it is an effective and safe therapeutic option to alleviate pain and improve functional capacity in patients with HA. Level of Evidence II, Systematic Review. Objective HA, , (HA) functionality life Methods publication databases PubMed Library EMBASE BVSBIREME BVS BIREME BVS/BIREME Scopus Science EBSCOhost 2020 word hemophilia diseases haemophilic Results 12 1 analysis 29 17 subjects observed Conclusion acid II Review (HA 202 2 20

The Committee of Latin America on the Therapeutics of Inhibitor Groups (CLOTTING) is composed of a number of hemophilia specialists from Latin America. The group aims to encourage the adoption of a good standard of care for Latin American patients with hemophilia. The occurrence of inhibitors in patients with hemophilia poses clinical challenges, and it is estimated that between 1000 and 3 000 patients in Latin America are affected by hemophilia with inhibitors. There is an urgent need to establish a regional consensus and clinical guidelines for the diagnosis and treatment of these patients. We present an extensive review based on best current clinical practice and published literature, as seen from a Latin American perspective, taking into account the variable nature of hemophilia care available in the various countries in this Region.

El Comité Latinoamericano sobre la Terapéutica de Personas con Inhibidores (CLOTTING) está compuesto por un grupo de especialistas en hemofilia de Latinoamérica. El objetivo del grupo es promover la adopción de un estándar de tratamiento óptimo para los pacientes con hemofilia en Latinoamérica. La prevalencia de inhibidores en pacientes con hemofilia en Latinoamérica determina desafíos clínicos y se estima que de 1000 a 3000 pacientes en esta región están afectados con hemofilia e inhibidores. Existe una necesidad urgente de establecer un consenso regional y guías clínicas para el diagnóstico y tratamiento de estos pacientes. Nosotros presentamos una revisión exhaustiva basada en las mejores prácticas clínicas vigentes y en los datos publicados en la literatura, con una perspectiva latinoamericana, tomando en cuenta la variabilidad existente de los tratamientos de la hemofilia disponibles en los diferentes países de esta Región.