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, Mark T Reding, S. Goranov, L. Gercheva, L. Rusen, V. Uscatescu, M. Pierdominici, S. Engelen, J. Pocoski, D. Walker, W. Hong

Research output: Contribution to journalArticle

15 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)2115-2124
Number of pages10
JournalJournal of Thrombosis and Haemostasis
Volume15
Issue number11
DOIs
StatePublished - Nov 1 2017

Fingerprint

Hemophilia A
Joint Diseases
Joints
Hemorrhage
Least-Squares Analysis
Quality of Life
Magnetic Resonance Imaging
Delivery of Health Care
Health
Therapeutics
Pain
Preexisting Condition Coverage
Factor VIII
Arthralgia
Chronic Pain
Sucrose
Randomized Controlled Trials

Keywords

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

Cite this

Manco-Johnson, M. J., Lundin, B., Funk, S., Peterfy, C., Raunig, D., Werk, M., ... 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

Effect of late prophylaxis in hemophilia on joint status : a randomized trial. / Manco-Johnson, M. J.; Lundin, B.; Funk, S.; Peterfy, C.; Raunig, D.; Werk, M.; Kempton, C. L.; Reding, Mark T; Goranov, S.; Gercheva, L.; Rusen, L.; Uscatescu, V.; Pierdominici, M.; Engelen, S.; Pocoski, J.; Walker, D.; Hong, W.

In: Journal of Thrombosis and Haemostasis, Vol. 15, No. 11, 01.11.2017, p. 2115-2124.

Research output: Contribution to journalArticle

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
Manco-Johnson MJ, Lundin B, Funk S, Peterfy C, Raunig D, Werk M et al. Effect of late prophylaxis in hemophilia on joint status: a randomized trial. Journal of Thrombosis and Haemostasis. 2017 Nov 1;15(11):2115-2124. https://doi.org/10.1111/jth.13811
Manco-Johnson, M. J. ; Lundin, B. ; Funk, S. ; Peterfy, C. ; Raunig, D. ; Werk, M. ; Kempton, C. L. ; Reding, Mark T ; Goranov, S. ; Gercheva, L. ; Rusen, L. ; Uscatescu, V. ; Pierdominici, M. ; Engelen, S. ; Pocoski, J. ; Walker, D. ; Hong, W. / Effect of late prophylaxis in hemophilia on joint status : a randomized trial. In: Journal of Thrombosis and Haemostasis. 2017 ; Vol. 15, No. 11. pp. 2115-2124.
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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.",
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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, {Mark 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",
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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, Mark 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.

PY - 2017/11/1

Y1 - 2017/11/1

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.

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KW - clinical trial

KW - hemophilia A

KW - magnetic resonance imaging

KW - prophylaxis

KW - quality of life

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