OBJECTIVES: While the advantages are well established for clotting factor replacement therapy in patients living with hemophilia, the degree of treatment adherence may impact these benefits. Treatment adherence may be challenging due to the mode of administration and frequency of self-administered injections or infusions, particularly among patients receiving prophylactic therapy. This systematic literature review aimed to investigate the effect of adherence to hemophilia treatment on clinical, humanistic, and economic outcomes.

METHODS: Literature searches were conducted in Embase, MEDLINE and MEDLINE In-Process, and Cochrane Library for English-language articles published from 22 June 2013 through 22 June 2023. Bibliographies of included studies were also searched for additional publications. Articles were screened for eligibility by two independent reviewers at abstract and full-text levels. This review included observational and qualitative studies.

RESULTS: Twenty articles were included after screening 722 citations. The studies examined relationships between treatment adherence and bleeding, joint health, inhibitor development, pain, quality of life, daily activity/work productivity, cognitive function, and healthcare resource use. Fourteen studies found that better adherence to hemophilia treatment in patients with hemophilia is associated with improved clinical, humanistic, and economic outcomes, including reduced bleeding risk, better joint structure and function, decreased chronic pain, improved health-related quality of life, reduced activity impairment, less school/work absenteeism, greater work productivity, and improved cognitive function. Significant differences in mean quality-of-life scores were observed between suboptimally adherent and adherent patients (74.1 vs. 81.2; P < 0.050). Heterogeneity across identified studies prevented the synthesis of results using meta-analysis.

CONCLUSIONS: This systematic literature review demonstrated associations between increased adherence to hemophilia treatment, specifically factor replacement therapy, and improved outcomes, suggesting that improvements in adherence would benefit patients. Future hemophilia treatment options that offer more convenience such as subcutaneous administration or less frequent dosing regimen may improve health outcomes by improving adherence.