Physical and Psychological Burden on People with Hemophilia: Global Real-World Data

Background: Although current and emerging prophylactic treatments can reduce bleeding risk for people with hemophilia (PWH), a residual physical and psychological burden associated with treatment may persist (Barry V et al. Haemophilia. 2021;27(3):375-382).

Aims: This study investigated the remaining clinical needs of people with hemophilia A (HA) and B (HB) receiving prophylaxis, from a global perspective. The current analysis assessed the physical and psychological burden reported by PWH.

Methods: This cross-sectional real-world survey captured patient-reported outcomes, experiences, and clinical data from PWH and parents/guardians of PWH (PPWH) in eight countries (Canada, France, Germany, India, Italy, Saudi Arabia, Spain and the US). Participants were recruited via interaction with treating healthcare professionals, social media, online panels and patient groups. Eligible participants were ≥1 year of age with HA and ≥6 months of prophylaxis or HB who were on prophylactic and/or on-demand treatment. Exclusions included mental incapacity, language barriers, clinical trial participation, or receipt of investigative/compassionate treatments.

Between December 2023 and March 2024, participants completed a 30-minute online survey. Disease impact on physical and psychological health was measured using the Patient-Reported Outcomes Measurement Information System 29+2 version 2.1 (PROMIS®-29+2 Profile v2.1 [PROMIS-29]), a validated questionnaire covering eight domains (physical functioning, ability to participate in social roles and activities, cognitive function, fatigue, sleep disturbance, pain interference, anxiety, and depressive symptoms). PROMIS-29 scores were transformed into T-scores using a reference sample from the general population with a mean of 50.

Lower scores for physical, social, and cognitive domains reflect higher burden, while higher scores for the other domains indicate greater burden. This analysis focuses on results for people with severe hemophilia without inhibitors (woI) by treatment class: standard half-life (SHL) and extended half-life (EHL) for factor VIII in HA or factor IX in HB, and non-factor therapy (NFT) in HA.

Results: Of 495 PWH/PPWH who completed the survey, most were self-completing PWH (n=323, 65%). Mean age (standard deviation, SD) of PWH was 27.1 (17.1) years. Of the 229 people with severe HAwoI 26% (n=59) received SHL, 28% (n=64) EHL, 40% (n=91) NFT and 6% (n=15) unknown. Of the 46 people with severe HBwoI 20% (n=9) received SHL, 78% EHL (n=36), and 2% (n=1) unknown.

Adult PROMIS-29 scores indicated that burden of disease for people with severe HAwoI in all domains was similar regardless of treatment class. Median scores (interquartile range) by treatment class, SHL (n=46)/EHL (n=36)/NFT (n=62), were 44 (38-57)/46 (41-57)/44 (39-57) for physical functioning, 48 (44-56)/52 (49-64)/52 (46-58) for social roles and activities, 56 (54-58)/56 (54-58)/58 (54-60) for sleep disturbance, and 59 (52-64)/56 (50-60)/56 (42-61) for pain interference. Similar results were observed for people with severe HBwoI, SHL (n=5)/EHL (n=21), at 46 (42-51)/48 (39-57) for physical functioning, 54 (50-60)/56 (46-64) for social roles and activities, 58 (57-60)/56 (54-58) for sleep disturbance, and 56 (53-57)/52 (42-61) for pain interference.

In response to two independent survey questions, people with severe HAwol (SHL [n=59]/EHL [n=64]/NFT [n=91]) reported feeling anxious (39%/38%/30%) or worried (34%/34%/26%), at least sometimes, that their treatment might not adequately protect them from bleeds. Corresponding responses for 45 people with severe HBwoI (SHL [n= 9]/EHL [n=36]) were 22%/22% (anxious) and 33%/31% (worried). The mean [SD] number of self-reported bleeds from people with severe HAwoI in the 12 months before the survey or since therapy switch was 6.8 [6.1] (SHL, n=59), 6.6 [9.7] (EHL, n=64), and 2.3 [4.2] (NFT, n=91). Corresponding mean [SD] self-reported bleeds from people with severe HBwoI were 3.2 [2.8] (SHL, n=9) and 4.8 [5.8] (EHL, n=36).

Conclusion: Assessing treatment burden using standard tools is an important part of comprehensive care to individually optimize care and outcomes. Irrespective of treatment class, individuals with severe hemophilia woI continue to experience physical burden from the disease, manifested as pain, sleep disturbances and psychological burden of anxiety, and worry about breakthrough bleeds.

Castaman:Bayer, BioMarin, Bioverativ, CSL Behring, LFB, Novo Nordisk, Pfizer, Roche, Sobi, Takeda: Honoraria; BioMarin, Bioviiix, CSL Behring, LFB, Novo Nordisk, Roche, Sobi, Takeda: Speakers Bureau. Percier:Novo Nordisk: Current Employment, Other: Shareholder. Shridhar:Novo Nordisk: Current Employment, Other: Shareholder. Reynolds:AbbVie, Bristol Myers Squibb, Eisai, Takeda, GlaxoSmithKline, ViiV, Novo Nordisk, Pfizer, Takeda, Plus Ultra Pharma (EU): Research Funding. Rajkovic-Hooley:AbbVie, Bristol Myers Squibb, Eisai, GlaxoSmithKline, Novo Nordisk, Novartis, Amgen, AstraZeneca, MSD, Kyowa Kirin: Research Funding; Adelphi Real World: Current Employment. Dewar:AbbVie, Astellas, AstraZeneca, Bristol Myers Squibb, Eli Lilly and Company, Gilead, Merck & Co, Novartis, Novo Nordisk.: Research Funding. Jiménez-Yuste:Novo Nordisk, Pfizer, Takeda, Sobi, Roche, CSL Behring, Bayer, Octapharma, BioMarin, Spark: Honoraria; Novo Nordisk, Pfizer, Takeda, Sobi, Roche, CSL Behring, Bayer, Octapharma, BioMarin, Spark: Consultancy; Pfizer, Takeda, Novo Nordisk, Sobi, Octapharma, Roche, Grifols, CSL Behring, Bayer: Research Funding.