Effect of late prophylaxis in hemophilia on joint status: a randomized trial

M. J. Manco-Johnson; B. Lundin; S. Funk; C. Peterfy; D. Raunig; M. Werk; C. L. Kempton; M. T. Reding; S. Goranov; L. Gercheva; L. Rusen; V. Uscatescu; M. Pierdominici; S. Engelen; J. Pocoski; D. Walker; W. Hong

doi:10.1111/jth.13811

Effect of late prophylaxis in hemophilia on joint status: a randomized trial

M. J. Manco-Johnson, B. Lundin, S. Funk, C. Peterfy, D. Raunig, M. Werk, C. L. Kempton, M. T. Reding, S. Goranov, L. Gercheva, L. Rusen, V. Uscatescu, M. Pierdominici, S. Engelen, J. Pocoski, D. Walker, W. Hong

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

98 Scopus citations

Abstract

Essentials High-quality data are lacking on use of prophylaxis in adults with hemophilia and arthropathy. SPINART was a 3-year randomized clinical trial of late/tertiary prophylaxis vs on-demand therapy. Prophylaxis improved function, quality of life, activity and pain but not joint structure by MRI. Prophylaxis improves function but must start before joint bleeding onset to prevent arthropathy. Summary: Background Limited data exist on the impact of prophylaxis on adults with severe hemophilia A and pre-existing joint disease. Objectives To describe 3-year bleeding, joint health and structure, health-related quality-of-life (HRQoL) and other outcomes from the open-label, randomized, multinational SPINART study. Patients/Methods Males aged 12–50 years with severe hemophilia A, ≥ 150 factor VIII exposure days, no inhibitors and no prophylaxis for > 12 consecutive months in the past 5 years were randomized to sucrose-formulated recombinant FVIII prophylaxis or on-demand therapy (OD). Data collected included total and joint bleeding events (BEs), joint structure (magnetic resonance imaging [MRI]), joint health (Colorado Adult Joint Assessment Scale [CAJAS]), HRQoL, pain, healthcare resource utilization (HRU), activity, and treatment satisfaction. Results Following 3 years of prophylaxis, adults maintained excellent adherence, with a 94% reduction in BEs despite severe pre-existing arthropathy; 35.7% and 76.2% of prophylaxis participants were bleed-free or had fewer than two BEs per year, respectively. As compared with OD, prophylaxis was associated with improved CAJAS scores (least squares [LS] mean, − 0.31 [n = 42] versus + 0.63 [n = 42]) and HAEMO-QoL-A scores (LS mean, + 3.98 [n = 41] versus − 6.00 [n = 42]), less chronic pain (50% decrease), and approximately two-fold less HRU; activity, Euro QoL-5D-3L (EQ-5D-3L) scores and satisfaction scores also favored prophylaxis. However, MRI score changes were not different for prophylaxis versus OD (LS mean, + 0.79 [n = 41] versus + 0.96 [n = 38]). Conclusions Over a period of 3 years, prophylaxis versus OD in adults with severe hemophilia A and arthropathy led to decreased bleeding, pain, and HRU, better joint health, activity, satisfaction, and HRQoL, but no reduction in structural arthropathy progression, suggesting that pre-existing joint arthropathy may be irreversible.

Original language	English (US)
Pages (from-to)	2115-2124
Number of pages	10
Journal	Journal of Thrombosis and Haemostasis
Volume	15
Issue number	11
DOIs	https://doi.org/10.1111/jth.13811
State	Published - Nov 2017

Bibliographical note

Funding Information:
This study was funded by Bayer AG (Leverkusen, Germany). MRI scans were read and scored by B. Lundin, C. Peterfy, and M. Werk. Medical writing assistance was provided by B. John of Complete Healthcare Communications, LLC (Chadds Ford, PA, USA) and was funded by Bayer.

Funding Information:
M. J. Manco-Johnson has received honoraria for advisory board participation from Bayer, Baxter BioScience, Biogen Idec, CSL Behring, and Novo Nordisk, and has received research grant funding from and has participated in a steering committee for Bayer. S. Funk developed, and M. J. Manco-Johnson implemented, the use of the CAJAS PT scale, which will be copyrighted. B. Lundin is employed by the Center for Medical Imaging and Physiology at Sk©ane University Hospital, has been under contract to Bayer for work performed for the cross-sectional study 12948, and is under contract for work performed for SPINART. S. Funk is a paid consultant on the Bayer-sponsored SPINART study. C. Peterfy received a grant from Bayer and personal fees from Spire Sciences, Inc. D. Raunig is employed by ICON Medical Imaging, and is under contract to Bayer for work performed for SPI-NART on the validation of the eMRI scale and CAJAS. M. Werk is under contract to Bayer for work performed for SPINART. M. T. Reding has received honoraria for advisory board participation from Baxter, Bayer, Biogen Idec, Octapharma, and Novo Nordisk, and has received speaking fees from Baxter, Biogen Idec, Novo Nordisk, and Pfizer. L. Rusen has received personal fees from Bayer. J. Pocoski and D. Walker are employees of Bayer. S. Engelen and W. Hong were employees of Bayer at the time this work was performed. The other authors state that they have no conflict of interest.

Publisher Copyright:
© 2017 The Authors. Journal of Thrombosis and Haemostasis published by Wiley Periodicals, Inc. on behalf of International Society on Thrombosis and Haemostasis.

Keywords

arthropathy
clinical trial
hemophilia A
magnetic resonance imaging
prophylaxis
quality of life

Publisher link

10.1111/jth.13811

Find It

Find It at U of M Libraries

Cite this

Manco-Johnson, M. J., Lundin, B., Funk, S., Peterfy, C., Raunig, D., Werk, M., Kempton, C. L., Reding, M. T., Goranov, S., Gercheva, L., Rusen, L., Uscatescu, V., Pierdominici, M., Engelen, S., Pocoski, J., Walker, D., & Hong, W. (2017). Effect of late prophylaxis in hemophilia on joint status: a randomized trial. Journal of Thrombosis and Haemostasis, 15(11), 2115-2124. https://doi.org/10.1111/jth.13811

Manco-Johnson, MJ, Lundin, B, Funk, S, Peterfy, C, Raunig, D, Werk, M, Kempton, CL, Reding, MT, Goranov, S, Gercheva, L, Rusen, L, Uscatescu, V, Pierdominici, M, Engelen, S, Pocoski, J, Walker, D & Hong, W 2017, 'Effect of late prophylaxis in hemophilia on joint status: a randomized trial', Journal of Thrombosis and Haemostasis, vol. 15, no. 11, pp. 2115-2124. https://doi.org/10.1111/jth.13811

@article{ac86c0b1c8fe46d7939a096e1387a48c,

title = "Effect of late prophylaxis in hemophilia on joint status: a randomized trial",

abstract = "Essentials High-quality data are lacking on use of prophylaxis in adults with hemophilia and arthropathy. SPINART was a 3-year randomized clinical trial of late/tertiary prophylaxis vs on-demand therapy. Prophylaxis improved function, quality of life, activity and pain but not joint structure by MRI. Prophylaxis improves function but must start before joint bleeding onset to prevent arthropathy. Summary: Background Limited data exist on the impact of prophylaxis on adults with severe hemophilia A and pre-existing joint disease. Objectives To describe 3-year bleeding, joint health and structure, health-related quality-of-life (HRQoL) and other outcomes from the open-label, randomized, multinational SPINART study. Patients/Methods Males aged 12–50 years with severe hemophilia A, ≥ 150 factor VIII exposure days, no inhibitors and no prophylaxis for > 12 consecutive months in the past 5 years were randomized to sucrose-formulated recombinant FVIII prophylaxis or on-demand therapy (OD). Data collected included total and joint bleeding events (BEs), joint structure (magnetic resonance imaging [MRI]), joint health (Colorado Adult Joint Assessment Scale [CAJAS]), HRQoL, pain, healthcare resource utilization (HRU), activity, and treatment satisfaction. Results Following 3 years of prophylaxis, adults maintained excellent adherence, with a 94% reduction in BEs despite severe pre-existing arthropathy; 35.7% and 76.2% of prophylaxis participants were bleed-free or had fewer than two BEs per year, respectively. As compared with OD, prophylaxis was associated with improved CAJAS scores (least squares [LS] mean, − 0.31 [n = 42] versus + 0.63 [n = 42]) and HAEMO-QoL-A scores (LS mean, + 3.98 [n = 41] versus − 6.00 [n = 42]), less chronic pain (50% decrease), and approximately two-fold less HRU; activity, Euro QoL-5D-3L (EQ-5D-3L) scores and satisfaction scores also favored prophylaxis. However, MRI score changes were not different for prophylaxis versus OD (LS mean, + 0.79 [n = 41] versus + 0.96 [n = 38]). Conclusions Over a period of 3 years, prophylaxis versus OD in adults with severe hemophilia A and arthropathy led to decreased bleeding, pain, and HRU, better joint health, activity, satisfaction, and HRQoL, but no reduction in structural arthropathy progression, suggesting that pre-existing joint arthropathy may be irreversible.",

keywords = "arthropathy, clinical trial, hemophilia A, magnetic resonance imaging, prophylaxis, quality of life",

author = "Manco-Johnson, {M. J.} and B. Lundin and S. Funk and C. Peterfy and D. Raunig and M. Werk and Kempton, {C. L.} and Reding, {M. T.} and S. Goranov and L. Gercheva and L. Rusen and V. Uscatescu and M. Pierdominici and S. Engelen and J. Pocoski and D. Walker and W. Hong",

note = "Funding Information: This study was funded by Bayer AG (Leverkusen, Germany). MRI scans were read and scored by B. Lundin, C. Peterfy, and M. Werk. Medical writing assistance was provided by B. John of Complete Healthcare Communications, LLC (Chadds Ford, PA, USA) and was funded by Bayer. Funding Information: M. J. Manco-Johnson has received honoraria for advisory board participation from Bayer, Baxter BioScience, Biogen Idec, CSL Behring, and Novo Nordisk, and has received research grant funding from and has participated in a steering committee for Bayer. S. Funk developed, and M. J. Manco-Johnson implemented, the use of the CAJAS PT scale, which will be copyrighted. B. Lundin is employed by the Center for Medical Imaging and Physiology at Sk{\textcopyright}ane University Hospital, has been under contract to Bayer for work performed for the cross-sectional study 12948, and is under contract for work performed for SPINART. S. Funk is a paid consultant on the Bayer-sponsored SPINART study. C. Peterfy received a grant from Bayer and personal fees from Spire Sciences, Inc. D. Raunig is employed by ICON Medical Imaging, and is under contract to Bayer for work performed for SPI-NART on the validation of the eMRI scale and CAJAS. M. Werk is under contract to Bayer for work performed for SPINART. M. T. Reding has received honoraria for advisory board participation from Baxter, Bayer, Biogen Idec, Octapharma, and Novo Nordisk, and has received speaking fees from Baxter, Biogen Idec, Novo Nordisk, and Pfizer. L. Rusen has received personal fees from Bayer. J. Pocoski and D. Walker are employees of Bayer. S. Engelen and W. Hong were employees of Bayer at the time this work was performed. The other authors state that they have no conflict of interest. Publisher Copyright: {\textcopyright} 2017 The Authors. Journal of Thrombosis and Haemostasis published by Wiley Periodicals, Inc. on behalf of International Society on Thrombosis and Haemostasis.",

year = "2017",

month = nov,

doi = "10.1111/jth.13811",

language = "English (US)",

volume = "15",

pages = "2115--2124",

journal = "Journal of Thrombosis and Haemostasis",

issn = "1538-7933",

publisher = "Wiley-Blackwell",

number = "11",

}

TY - JOUR

T1 - Effect of late prophylaxis in hemophilia on joint status

T2 - a randomized trial

AU - Manco-Johnson, M. J.

AU - Lundin, B.

AU - Funk, S.

AU - Peterfy, C.

AU - Raunig, D.

AU - Werk, M.

AU - Kempton, C. L.

AU - Reding, M. T.

AU - Goranov, S.

AU - Gercheva, L.

AU - Rusen, L.

AU - Uscatescu, V.

AU - Pierdominici, M.

AU - Engelen, S.

AU - Pocoski, J.

AU - Walker, D.

AU - Hong, W.

N1 - Funding Information: This study was funded by Bayer AG (Leverkusen, Germany). MRI scans were read and scored by B. Lundin, C. Peterfy, and M. Werk. Medical writing assistance was provided by B. John of Complete Healthcare Communications, LLC (Chadds Ford, PA, USA) and was funded by Bayer. Funding Information: M. J. Manco-Johnson has received honoraria for advisory board participation from Bayer, Baxter BioScience, Biogen Idec, CSL Behring, and Novo Nordisk, and has received research grant funding from and has participated in a steering committee for Bayer. S. Funk developed, and M. J. Manco-Johnson implemented, the use of the CAJAS PT scale, which will be copyrighted. B. Lundin is employed by the Center for Medical Imaging and Physiology at Sk©ane University Hospital, has been under contract to Bayer for work performed for the cross-sectional study 12948, and is under contract for work performed for SPINART. S. Funk is a paid consultant on the Bayer-sponsored SPINART study. C. Peterfy received a grant from Bayer and personal fees from Spire Sciences, Inc. D. Raunig is employed by ICON Medical Imaging, and is under contract to Bayer for work performed for SPI-NART on the validation of the eMRI scale and CAJAS. M. Werk is under contract to Bayer for work performed for SPINART. M. T. Reding has received honoraria for advisory board participation from Baxter, Bayer, Biogen Idec, Octapharma, and Novo Nordisk, and has received speaking fees from Baxter, Biogen Idec, Novo Nordisk, and Pfizer. L. Rusen has received personal fees from Bayer. J. Pocoski and D. Walker are employees of Bayer. S. Engelen and W. Hong were employees of Bayer at the time this work was performed. The other authors state that they have no conflict of interest. Publisher Copyright: © 2017 The Authors. Journal of Thrombosis and Haemostasis published by Wiley Periodicals, Inc. on behalf of International Society on Thrombosis and Haemostasis.

PY - 2017/11

Y1 - 2017/11

N2 - Essentials High-quality data are lacking on use of prophylaxis in adults with hemophilia and arthropathy. SPINART was a 3-year randomized clinical trial of late/tertiary prophylaxis vs on-demand therapy. Prophylaxis improved function, quality of life, activity and pain but not joint structure by MRI. Prophylaxis improves function but must start before joint bleeding onset to prevent arthropathy. Summary: Background Limited data exist on the impact of prophylaxis on adults with severe hemophilia A and pre-existing joint disease. Objectives To describe 3-year bleeding, joint health and structure, health-related quality-of-life (HRQoL) and other outcomes from the open-label, randomized, multinational SPINART study. Patients/Methods Males aged 12–50 years with severe hemophilia A, ≥ 150 factor VIII exposure days, no inhibitors and no prophylaxis for > 12 consecutive months in the past 5 years were randomized to sucrose-formulated recombinant FVIII prophylaxis or on-demand therapy (OD). Data collected included total and joint bleeding events (BEs), joint structure (magnetic resonance imaging [MRI]), joint health (Colorado Adult Joint Assessment Scale [CAJAS]), HRQoL, pain, healthcare resource utilization (HRU), activity, and treatment satisfaction. Results Following 3 years of prophylaxis, adults maintained excellent adherence, with a 94% reduction in BEs despite severe pre-existing arthropathy; 35.7% and 76.2% of prophylaxis participants were bleed-free or had fewer than two BEs per year, respectively. As compared with OD, prophylaxis was associated with improved CAJAS scores (least squares [LS] mean, − 0.31 [n = 42] versus + 0.63 [n = 42]) and HAEMO-QoL-A scores (LS mean, + 3.98 [n = 41] versus − 6.00 [n = 42]), less chronic pain (50% decrease), and approximately two-fold less HRU; activity, Euro QoL-5D-3L (EQ-5D-3L) scores and satisfaction scores also favored prophylaxis. However, MRI score changes were not different for prophylaxis versus OD (LS mean, + 0.79 [n = 41] versus + 0.96 [n = 38]). Conclusions Over a period of 3 years, prophylaxis versus OD in adults with severe hemophilia A and arthropathy led to decreased bleeding, pain, and HRU, better joint health, activity, satisfaction, and HRQoL, but no reduction in structural arthropathy progression, suggesting that pre-existing joint arthropathy may be irreversible.

AB - Essentials High-quality data are lacking on use of prophylaxis in adults with hemophilia and arthropathy. SPINART was a 3-year randomized clinical trial of late/tertiary prophylaxis vs on-demand therapy. Prophylaxis improved function, quality of life, activity and pain but not joint structure by MRI. Prophylaxis improves function but must start before joint bleeding onset to prevent arthropathy. Summary: Background Limited data exist on the impact of prophylaxis on adults with severe hemophilia A and pre-existing joint disease. Objectives To describe 3-year bleeding, joint health and structure, health-related quality-of-life (HRQoL) and other outcomes from the open-label, randomized, multinational SPINART study. Patients/Methods Males aged 12–50 years with severe hemophilia A, ≥ 150 factor VIII exposure days, no inhibitors and no prophylaxis for > 12 consecutive months in the past 5 years were randomized to sucrose-formulated recombinant FVIII prophylaxis or on-demand therapy (OD). Data collected included total and joint bleeding events (BEs), joint structure (magnetic resonance imaging [MRI]), joint health (Colorado Adult Joint Assessment Scale [CAJAS]), HRQoL, pain, healthcare resource utilization (HRU), activity, and treatment satisfaction. Results Following 3 years of prophylaxis, adults maintained excellent adherence, with a 94% reduction in BEs despite severe pre-existing arthropathy; 35.7% and 76.2% of prophylaxis participants were bleed-free or had fewer than two BEs per year, respectively. As compared with OD, prophylaxis was associated with improved CAJAS scores (least squares [LS] mean, − 0.31 [n = 42] versus + 0.63 [n = 42]) and HAEMO-QoL-A scores (LS mean, + 3.98 [n = 41] versus − 6.00 [n = 42]), less chronic pain (50% decrease), and approximately two-fold less HRU; activity, Euro QoL-5D-3L (EQ-5D-3L) scores and satisfaction scores also favored prophylaxis. However, MRI score changes were not different for prophylaxis versus OD (LS mean, + 0.79 [n = 41] versus + 0.96 [n = 38]). Conclusions Over a period of 3 years, prophylaxis versus OD in adults with severe hemophilia A and arthropathy led to decreased bleeding, pain, and HRU, better joint health, activity, satisfaction, and HRQoL, but no reduction in structural arthropathy progression, suggesting that pre-existing joint arthropathy may be irreversible.

KW - arthropathy

KW - clinical trial

KW - hemophilia A

KW - magnetic resonance imaging

KW - prophylaxis

KW - quality of life

UR - http://www.scopus.com/inward/record.url?scp=85031100528&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85031100528&partnerID=8YFLogxK

U2 - 10.1111/jth.13811

DO - 10.1111/jth.13811

M3 - Article

C2 - 28836341

AN - SCOPUS:85031100528

SN - 1538-7933

VL - 15

SP - 2115

EP - 2124

JO - Journal of Thrombosis and Haemostasis

JF - Journal of Thrombosis and Haemostasis

IS - 11

ER -

Effect of late prophylaxis in hemophilia on joint status: a randomized trial

Abstract

Bibliographical note

Keywords

Publisher link

Find It

Other files and links

Fingerprint

Cite this