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. 2021 Dec 18;10(24):5959.
doi: 10.3390/jcm10245959.

Real-World Rates of Bleeding, Factor VIII Use, and Quality of Life in Individuals with Severe Haemophilia A Receiving Prophylaxis in a Prospective, Noninterventional Study

Gili Kenet  1 , Yeu-Chin Chen  2 , Gillian Lowe  3 , Charles Percy  3 , Huyen Tran  4 , Annette von Drygalski  5 , Marc Trossaërt  6 , Mark Reding  7 , Johannes Oldenburg  8 , Maria Eva Mingot-Castellano  9 , Young-Shil Park  10 , Flora Peyvandi  11   12 , Margareth C Ozelo  13 , Johnny Mahlangu  14 , Jennifer Quinn  15 , Mei Huang  16 , Divya B Reddy  16 , Benjamin Kim  16
Affiliations

Real-World Rates of Bleeding, Factor VIII Use, and Quality of Life in Individuals with Severe Haemophilia A Receiving Prophylaxis in a Prospective, Noninterventional Study

Gili Kenet et al. J Clin Med. .

Abstract

Regular prophylaxis with exogenous factor VIII (FVIII) is recommended for individuals with severe haemophilia A (HA), but standardised data are scarce. Here, we report real-world data from a global cohort. Participants were men ≥18 years old with severe HA (FVIII ≤ 1 IU/dL) receiving regular prophylaxis with FVIII. Participants provided 6 months of retrospective data and were prospectively followed for up to 12 months. Annualised bleeding rate (ABR) and FVIII utilisation and infusion rates were calculated. Differences between geographic regions were explored. Of 294 enrolled participants, 225 (76.5%) completed ≥6 months of prospective follow-up. Pre-baseline and on-study, the median (range) ABR values for treated bleeds were 2.00 (0-86.0) and 1.85 (0-37.8), respectively; the median (range) annualised FVIII utilisation rates were 3629.0 (1008.5-13541.7) and 3708.0 (1311.0-14633.4) IU/kg/year, respectively; and the median (range) annualised FVIII infusion rates were 120.0 (52.0-364.0) and 122.4 (38.0-363.8) infusions/year, respectively. The median (range) Haemo-QoL-A Total Score was 76.3 (9.4-100.0) (n = 289), ranging from 85.1 in Australia to 67.7 in South America. Physical Functioning was the most impacted Haemo-QoL-A domain in 4/6 geographic regions. Despite differences among sites, participants reported bleeding requiring treatment and impaired physical functioning. These real-world data illustrate shortcomings associated with FVIII prophylaxis for this global cohort of individuals with severe HA.

Keywords: FVIII prophylaxis; haemophilia A; noninterventional study.

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Conflict of interest statement

Gili Kenet reports research support from Alnylam, Bayer, Opko Biologics, Pfizer, and Shire, as well as honoraria for consultancy from Alnylam, Bayer, Novo Nordisk, Pfizer, Roche, and Takeda. Yeu-Chin Chen, Gillian Lowe, Charles Percy, Huyen Tran, and Young Shil Park report nothing to disclose. Marc Trossaërt reports research support from Takeda, CSL Behring, Novo Nordisk, and SOBI, as well as consulting honoraria from Takeda, CSL Behring, and Roche. Annette von Drygalski has received fees from BioMarin, Bioverativ/Sanofi Genzyme, Novo Nordisk, Pfizer, Takeda, and UniQure for participation in industry-sponsored education events and advisory boards. She is cofounder and a member of the board of directors of Hematherix Inc. She holds a patent for a super FVa and is the inventor and physician lead for the Joint Activity and Damage Examination (JADE) ultrasound measurement tool. The JADE measurement tool is copyrighted and is commercialised through a partnership between the University of California, the University of San Diego School of Medicine, and the Hemophilia and Thrombosis Treatment Center at the University of San Diego, California, of which she is medical director. Mark Reding reports receiving honoraria for participation on advisory boards and/or speakers bureaus from Bayer, CSL Behring, Novo Nordisk, Sanofi Genzyme, and Takeda, as well as grant funding from Bayer and BioMarin Pharmaceutical Inc. Johannes Oldenburg has received reimbursements for attending symposia/congresses, honoraria for speaking or for consulting, or funds for research from Bayer, Biogen Idec, Biotest, Chugai, CSL Behring, Grifols, Novo Nordisk, Octapharma, Pfizer, Roche, Shire, and SOBI. Maria Mingot-Castellano reports receiving honoraria for consulting or lecturing for Novo Nordisk, Grifols, Baxter, and Wyeth. Flora Peyvandi reports receiving honoraria as a speaker for educational symposia by Grifols, Sanofi, and Takeda and advisory member for Sanofi and Roche. Margareth C Ozelo reports consulting payments from Bayer, BioMarin Pharmaceutical Inc., Novo Nordisk, Pfizer, Roche, Sanofi, and Takeda; research grants from Pfizer, Roche, and Takeda; participation as a clinical trial investigator for BioMarin Pharmaceutical Inc., Novo Nordisk, Pfizer, Roche, Sanofi, and Takeda; speaker fees/payments from Bayer, BioMarin Pharmaceutical Inc., Novo Nordisk, Roche, and Takeda; travel support from Novo Nordisk, Roche, and Takeda; and participation in grant review for Grifols. Johnny Mahlangu reports consulting payments from Baxalta, Catalyst BioSciences, CSL Behring, Freeline, LFB, Novo Nordisk, and Spark; research grants from BioMarin Pharmaceutical Inc., CSL Behring, Novartis, Novo Nordisk, Pfizer, Roche, Sanofi, Sobi, and UniQure; participation as a clinical trial investigator for BioMarin Pharmaceutical Inc., CSL Behring, Novartis, Novo Nordisk, Pfizer, Roche, Sanofi, Sobi, and UniQure; receiving speaker fees/payments from Novo Nordisk, Pfizer, Roche, Sanofi, Shire, Sobi, Takeda, ISTH, and WFH; and travel support from ISTH, Novo Nordisk, Pfizer, Roche, Sanofi, Shire, Sobi, Takeda, and WFH. Jennifer Quinn and Divya B Reddy are employees and stockholders of BioMarin Pharmaceutical, Inc. Mei Huang and Benjamin Kim are former employees of BioMarin Pharmaceutical, Inc. and may hold stock.

Figures

Figure 1
Figure 1
Patient disposition. a Reasons for screen failure: no history of FVIII inhibitor and results from a Bethesda assay, n = 8; significant liver dysfunction with abnormal laboratory results, n = 3; active hepatitis C, n = 6; chronic or active hepatitis B, n = 1; concurrent enrolment in another clinical study, n = 2; ability to comply with protocol requirements per Investigator, n = 2; male ≥18 years of age with residual FVIII ≤1, n = 1; must have been on prophylaxis FVIII for ≥6 months prior, n = 4. b Completing 6 months on-study was not required for participants not rolling over into the interventional study. AAV5 TAb, adeno-associated virus vector total antibody; FVIII, factor VIII.
Figure 2
Figure 2
Median (range) overall transformed Haemo-QoL-A total and domain scores at baseline (A) for all participants globally (n = 298) and (B) for participants by region. Haemo-QoL-A scores range from 0 to 100, with higher scores indicating higher quality of life. a Belgium, Germany, Spain, France, UK, Israel, and Italy. For total score, n = 90; Physical functioning, n = 94; Role functioning, n = 94; Worry, n = 91; Consequences of bleeding, n = 93; Emotional impact, n = 91; Treatment concern, n = 94. b Brazil. c Korea and Taiwan. d US. e South Africa. Haemo-QoL-A, haemophilia-specific health-related quality of life questionnaire for adults; SD, standard deviation.
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