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. 2021 Oct 14:12:883-896.
doi: 10.2147/JBM.S327180. eCollection 2021.

A Prospective Observational Study of Antihemophilic Factor (Recombinant) Prophylaxis Related to Physical Activity Levels in Patients with Hemophilia A in the United States (SPACE)

Barbara A Konkle  1 , Doris V Quon  2 , Leslie Raffini  3 , Michael Recht  4 , Vlad C Radulescu  5 , Shannon L Carpenter  6 , Amy L Dunn  7 , Mei Lu  8 , Maureen Watt  9
Affiliations

A Prospective Observational Study of Antihemophilic Factor (Recombinant) Prophylaxis Related to Physical Activity Levels in Patients with Hemophilia A in the United States (SPACE)

Barbara A Konkle et al. J Blood Med. .

Abstract

Introduction: High collision-risk physical activity can increase bleeding risk in people with hemophilia A, as can increasing the time between factor VIII (FVIII) administration and physical activity. FVIII prophylaxis may be tailored to planned activities to prevent activity-related bleeding.

Aim: To explore the relationship between physical activity levels, FVIII infusion timing, and occurrence of bleeding in patients with severe/moderately severe hemophilia A without FVIII inhibitors receiving antihemophilic factor (recombinant) (rAHF; ADVATE®; Baxalta US Inc., a Takeda company, Lexington, MA, USA).

Methods: SPACE was a 6-month, prospective, multicenter, observational outcomes study (NCT02190149). Enrolled patients received an eDiary application and a wearable activity tracker, which recorded physical activity, rAHF infusion, and occurrence of bleeding. Physical activity risks were ranked using National Hemophilia Foundation criteria.

Results: Fifty-four patients aged 11-58 years (n = 47 prophylaxis, n = 7 on-demand) were included in the analysis. Patients had a mean (SD) 8.14 (10.94) annualized bleeding rate, and recorded 4980 intervals between an rAHF infusion and physical activity; 1759 (35.3%) of these intervals were ≤24 hours. Analysis of recorded eDiary data showed that the risk of activity-related bleeding did not significantly increase with time between last infusion and activity, but did increase with higher-risk physical activities. Analysis of activity tracker recorded data showed that the risk of bleeding reported by patients as spontaneous increased with prolonging time (≤24 to >24 hours) from last infusion to physical activity start (odds ratio 2.65, p < 0.05). Joint health data collected at baseline were not included in the regression analysis because of small sample size; therefore the study could not assess whether patients with more joint disease at baseline were at higher risk of injury-related and reported spontaneous occurrence of bleeding.

Conclusion: These results show that activities with a high risk of collision lead to an increased risk of bleeding. Further investigation is warranted to explore potential benefits of FVIII infusion timing to reduce the risks of activity-related occurrence of bleeding.

Keywords: bleeding; hemophilia A; physical activity; post-authorization study; prophylaxis; recombinant factor VIII.

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Conflict of interest statement

BAK has received research support from Baxalta, Pfizer, Sanofi, Sigilon, Takeda, and Uniqure; and consulting fees from BioMarin, CSL Behring, Pfizer, Sanofi, Takeda, Sigilon, Spark, and Uniqure. DVQ has received consulting fees/honoraria from Bayer, BioMarin, Genentech, Novo Nordisk, Sanofi, and Octapharma; and has been a speaker for BioMarin, Genentech, Novo Nordisk, Sanofi, and Takeda. LR has participated on advisory boards for Bayer, CSL Behring, Genentech, Roche, HemaBiologics, and XaTek. MR has received research support for Oregon Health & Science University from BioMarin, Bioverativ/Sanofi, Catalyst Biosciences, Genentech, Hema Biologics, Novo Nordisk, Shire/Takeda, Spark, and uniQure; has been a consultant for the American Thrombosis and Hemostasis Network, Bayer, Bioverativ/Sanofi, CSL Behring, Genentech, Grifols, Kedrion, LFB, Novo Nordisk, Octapharma, Pfizer, Shire/Takeda, and uniQure; has been on the board of directors of the Foundation for Women and Girls with Blood Disorders and Partners in Bleeding Disorders; and is an employee of Oregon Health & Science University. VCR has received research support from Grifols, Pfizer, and Takeda. SLC has received honoraria from CSL Behring, Genentech, Kedrion, and Novo Nordisk; has received research support from the American Thrombosis and Hemostasis Network; and has been on the board of directors for the American Thrombosis and Hemostasis Network and the Hemostasis and Thrombosis Research Society. ALD has received research support from BioMarin and Takeda; and personal fees from CSL Behring, Genentech, Medscape, and uniQure. ML is an employee of Shire US Inc., a Takeda company, and a Takeda stock owner. MW is an employee of Shire International GmbH, a Takeda company, and a Takeda stock owner. The authors report no other conflicts of interest in this work.

Figures

Figure 1
Figure 1
(A) SPACE study design and timing of assessments. (B) Patient disposition. †For inactivity (n = 1), loss to follow-up (n = 1), non-compliance with required reporting (n = 1), or non-compliance with data entry (n = 1). ‡Technical problems, difficulty committing time (n = 6); non-compliance, withdrew consent (n = 5). §Non-compliance (n = 1) and technical difficulties (withdrawn per protocol; n = 2). Other data includes number of concomitant medications, non-drug therapies and available pharmacokinetic data history. ††Completed 1 week before study end.
Figure 2
Figure 2
Annualized bleeding rates (ABR) at study end by treatment regimen. (A) All bleeds. (B) Joint bleeds. †Patients with ≥5 months of follow-up data.
See this image and copyright information in PMC

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