Burden of mild haemophilia A: Systematic literature review

Abstract

This is an open access article under the terms of the Creat ive Commo ns Attri butio n-NonCo mmerc ial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. Abstract Introduction: Although the clinical manifestations of severe haemophilia A (HA) are well studied, the challenges, if any, of living with mild HA are not clearly delineated to date. Aim: To assess available evidence of clinical risks and societal/economic impacts of disease in adult patients with mild HA using a systematic literature review. Methods: Prespecified study selection criteria were applied in a comprehensive literature search. Included studies varied in design and reported outcomes of interest for adults (≥13 years of age) with mild HA.Results: Seventeen studies with a total of 3213 patients met eligibility criteria (published or presented in English, 1966(published or presented in English, -2017. Most studies were observational, and the outcomes reported were too sparse and dissimilar to support a formal meta-analysis.Mean annual bleeding rates ranged from 0.44 to 4.5 episodes per patient per year.Quality of life (QoL; SF-36 General Health) was impacted compared to healthy controls. Health care costs and productivity were seldom assessed and no robust comparisons to healthy controls were available. Conclusion:Quantifying outcomes for adult patients with mild HA remains challenging, with estimates of key QoL and cost data often based on small data sets and without comparison to population norms. Therefore, the clinical impact of mild haemophilia may be under-represented and unmet needs may remain unaddressed. As paradigm-changing therapies for HA emerge, stronger knowledge of mild HA can guide the development of care options that minimize burden and enhance the QoL for this segment of the haemophilia community, and for the haemophilia community in totality. K E Y W O R D Sacute bleeding, disease burden, haemophilia, quality of life

Non‐severe haemophilia: Is it benign? – Insights from the PROBE study

“…The burden of mild haemophilia A was systematically reviewed by Peyvandi et al 10 and it highlighted the issue of bias in studies due to a variety of reasons. To address issues of bias in reporting the impact of mild and moderate haemophilia, multivariate analyses indicate there was a reduction in all health utility values in respondents with mild and moderate haemophilia keeping all other variables constant.…”

Impact of haemophilia on patients with mild‐to‐moderate disease: Results from the P‐FiQ and B‐HERO‐S studies

“…Multiple studies have been conducted to determine the psychosocial and physical impact of haemophilia on patients and their caregivers 1‐9 . Many of these studies focused only on men or severe haemophilia 1,3,4,6‐9 ; however, epidemiologic studies suggest that joint bleeding occurs in patients with mild‐to‐moderate haemophilia, 10‐12 including women and girls 13‐15 . Importantly, some bleeds result in impairments in joint function and significantly influence quality of life 16‐18 …”

Identified unmet needs and proposed solutions in mild‐to‐moderate haemophilia: A summary of opinions from a roundtable of haemophilia experts

“…Scientific publications focused on mild‐to‐moderate haemophilia are clearly lacking and are needed to better assess bleeding rates and consequences 8 . This is of importance given the debate on acceptable factor levels with prophylaxis, new non‐factor treatments and gene therapy.…”

“…Articles summarizing the impact of mild‐to‐moderate haemophilia in men and women should include issues with health‐related quality of life, including pain, anxiety and depression, and functional impairment over the long‐term. In addition, clinical burden, financial burden and societal impacts for this population have not been well‐studied 8 …”

“…There is a significant lack of data on patients with mild‐to‐moderate haemophilia. These patients are often not included in clinical trials 1 or studies concerning quality of life, outcomes, disease burden or financial impact of disease 8 . A meta‐analysis was recently attempted; however, the available information was so sparse that the analysis was not possible 8 …”