A literature review has failed to provide new insights regarding the burden of mild hemophilia A.
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In the 17 studies reviewed, mean annual bleeding rates (ABRs) were largely unreported. Data on joint pain and damage, quality of life (QOL), societal impacts, and costs of care were limited and inconsistent across the studies.
The review “revealed a lack of evidence” in adults with mild hemophilia A, Flora Peyvandi, MD, PhD, of Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico in Milan and colleagues wrote in Haemophilia.
The researchers reviewed data from 10 studies conducted in Europe, 6 in North America, and 1 in Japan. Six studies were prospective cohort or registry studies, six were retrospective, and five studies were surveys or outcomes research.
The studies included 3,213 patients with mild hemophilia A aged 13 years or older. There were few details on treatment protocols, but patients received factor VIII concentrates, recombinant factor VIII, and desmopressin.
Most studies did not report mean ABRs. For the three that did, the mean ABRs were 0.44, 0.56, and 4.5. Six studies reported the percentage of patients with bleeding events, and those numbers ranged from 5.5% (1/18) to 90.7% (68/75).
Data on joint pain and damage were not standardized across studies, so the researchers were unable to draw any conclusions. One study showed no significant difference in Health Assessment Questionnaire pain score between patients with mild hemophilia A and control subjects. In another study, 5% of patients with mild hemophilia A reported having severe joint pain in the previous year, and 15% of patients reported moderate joint pain.
The researchers also found it difficult to draw conclusions about QOL. Three studies reported QOL data, and all used a different instrument.
In a study using the SF-36, general health and emotional role functioning were both significantly lower for patients with mild hemophilia A than for age-matched healthy control subjects (P less than .05). In a study using the SF-12, the physical component summary was significantly higher for patients with mild hemophilia A than for those with severe disease (P = .014).
In a study using the Haemo-QOL-A, there were no significant differences between patients with mild and severe hemophilia A. However, Dr. Peyvandi and colleagues noted that this study required long-term use of factor VIII concentrate, so the mild hemophilia A patients in this group were “probably not representative” of the overall mild hemophilia A population.
Societal impacts were difficult to assess because of a lack of standardization across studies. One study showed no significant difference in employment between patients with mild hemophilia A and healthy controls. In a U.S.-based study, patients with mild hemophilia A missed an average of 6.2 workdays per year, and 4.7 days were caused by their hemophilia. A study in Italy showed that patients with mild hemophilia A missed an average of 3.4 workdays per year.
Just two studies included data on health care costs for patients with mild hemophilia A. The mean cost of care was €793 per year in a study from Portugal published in 2015. In a U.S. study published in 1995, the annual cost of care was $22,182.
“Considering the limitations of the current body of evidence, higher-quality studies in this area are needed,” Dr. Peyvandi and colleagues wrote. “Such studies would report both bleeding and other clinical outcomes based on common definitions and for a representative population of mild [hemophilia A] adults. Areas for further research include more robust comparison to healthy controls or population norms, especially for QOL and other patient-reported outcomes.”
Seven of the eight researchers reported relationships, including employment, with BioMarin. Dr. Peyvandi reported relationships with Sanofi, Grifols, Novo Nordisk, Roche, Takeda, Sobi, Bioverativ, Spark Therapeutics, Sysmex, and CSL Behring.
SOURCE: Peyvandi F et al. Haemophilia. 2019 Jul 11. doi: 10.1111/hae.13777.