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; Yeu Chin Chen; Gillian Lowe; Charles Percy; Huyen Tran; Annette von Drygalski; Marc Trossaërt; Mark Reding; Johannes Oldenburg; Maria Eva Mingot-Castellano; Young Shil Park; Flora Peyvandi; Margareth C. Ozelo; Johnny Mahlangu; Jennifer Quinn; Mei Huang; Divya B. Reddy; Benjamin Kim

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, Yeu Chin Chen, Gillian Lowe, Charles Percy, Huyen Tran, Annette von Drygalski, Marc Trossaërt, Mark Reding, Johannes Oldenburg, Maria Eva Mingot-Castellano, Young Shil Park, Flora Peyvandi, Margareth C. Ozelo, Johnny Mahlangu, Jennifer Quinn, Mei Huang, Divya B. Reddy, Benjamin Kim

Medicine - Hematology, Oncology, Transplant

Research output: Contribution to journal › Article › peer-review

17 Scopus citations

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.

Original language	English (US)
Article number	5959
Journal	Journal of Clinical Medicine
Volume	10
Issue number	24
DOIs	https://doi.org/10.3390/jcm10245959
State	Published - Dec 1 2021

Bibliographical note

Funding Information:
Funding: This study was sponsored by BioMarin Pharmaceutical Inc. (Novato, CA, USA).

Funding Information:
Acknowledgments: We thank the study participants, study site personnel, and investigators contributing to the 270-902 study. Assistance in medical writing and editorial support were provided by Kathleen Pieper and Elisabetta Lauretti of AlphaBioCom, LLC, and funding was provided by BioMarin Pharmaceutical Inc. Project management support was provided by Sara Hawley of BioMarin Pharmaceutical Inc.

Funding Information:
Conflicts of Interest: 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.

Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Keywords

FVIII prophylaxis
Noninterventional study
haemophilia A

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10.3390/jcm10245959

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Kenet, G., Chen, Y. C., Lowe, G., Percy, C., Tran, H., von Drygalski, A., Trossaërt, M., Reding, M., Oldenburg, J., Mingot-Castellano, M. E., Park, Y. S., Peyvandi, F., Ozelo, M. C., Mahlangu, J., Quinn, J., Huang, M., Reddy, D. B., & Kim, B. (2021). 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. Journal of Clinical Medicine, 10(24), Article 5959. https://doi.org/10.3390/jcm10245959

Kenet, G, Chen, YC, Lowe, G, Percy, C, Tran, H, von Drygalski, A, Trossaërt, M, Reding, M, Oldenburg, J, Mingot-Castellano, ME, Park, YS, Peyvandi, F, Ozelo, MC, Mahlangu, J, Quinn, J, Huang, M, Reddy, DB & Kim, B 2021, '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', Journal of Clinical Medicine, vol. 10, no. 24, 5959. https://doi.org/10.3390/jcm10245959

@article{b9956adf5e744f7f8089d7ab99e835ae,

title = "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",

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, Noninterventional study, haemophilia A",

author = "Gili Kenet and Chen, {Yeu Chin} and Gillian Lowe and Charles Percy and Huyen Tran and {von Drygalski}, Annette and Marc Trossa{\"e}rt and Mark Reding and Johannes Oldenburg and Mingot-Castellano, {Maria Eva} and Park, {Young Shil} and Flora Peyvandi and Ozelo, {Margareth C.} and Johnny Mahlangu and Jennifer Quinn and Mei Huang and Reddy, {Divya B.} and Benjamin Kim",

note = "Funding Information: Funding: This study was sponsored by BioMarin Pharmaceutical Inc. (Novato, CA, USA). Funding Information: Acknowledgments: We thank the study participants, study site personnel, and investigators contributing to the 270-902 study. Assistance in medical writing and editorial support were provided by Kathleen Pieper and Elisabetta Lauretti of AlphaBioCom, LLC, and funding was provided by BioMarin Pharmaceutical Inc. Project management support was provided by Sara Hawley of BioMarin Pharmaceutical Inc. Funding Information: Conflicts of Interest: 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 Trossa{\"e}rt 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. Publisher Copyright: {\textcopyright} 2021 by the authors. Licensee MDPI, Basel, Switzerland.",

year = "2021",

month = dec,

day = "1",

doi = "10.3390/jcm10245959",

language = "English (US)",

volume = "10",

journal = "Journal of Clinical Medicine",

issn = "2077-0383",

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}

TY - JOUR

T1 - 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

AU - Kenet, Gili

AU - Chen, Yeu Chin

AU - Lowe, Gillian

AU - Percy, Charles

AU - Tran, Huyen

AU - von Drygalski, Annette

AU - Trossaërt, Marc

AU - Reding, Mark

AU - Oldenburg, Johannes

AU - Mingot-Castellano, Maria Eva

AU - Park, Young Shil

AU - Peyvandi, Flora

AU - Ozelo, Margareth C.

AU - Mahlangu, Johnny

AU - Quinn, Jennifer

AU - Huang, Mei

AU - Reddy, Divya B.

AU - Kim, Benjamin

N1 - Funding Information: Funding: This study was sponsored by BioMarin Pharmaceutical Inc. (Novato, CA, USA). Funding Information: Acknowledgments: We thank the study participants, study site personnel, and investigators contributing to the 270-902 study. Assistance in medical writing and editorial support were provided by Kathleen Pieper and Elisabetta Lauretti of AlphaBioCom, LLC, and funding was provided by BioMarin Pharmaceutical Inc. Project management support was provided by Sara Hawley of BioMarin Pharmaceutical Inc. Funding Information: Conflicts of Interest: 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. Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

PY - 2021/12/1

Y1 - 2021/12/1

N2 - 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.

AB - 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.

KW - FVIII prophylaxis

KW - Noninterventional study

KW - haemophilia A

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UR - http://www.scopus.com/inward/citedby.url?scp=85121327979&partnerID=8YFLogxK

U2 - 10.3390/jcm10245959

DO - 10.3390/jcm10245959

M3 - Article

C2 - 34945255

AN - SCOPUS:85121327979

SN - 2077-0383

VL - 10

JO - Journal of Clinical Medicine

JF - Journal of Clinical Medicine

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M1 - 5959

ER -

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

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