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

Abstract

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 Watt9 1Department of Medicine, The University of Washington and Bloodworks Northwest, Seattle, WA, USA; 2Orthopaedic Hemophilia Treatment Center, Orthopaedic Institute for Children, Los Angeles, CA, USA; 3Division of Hematology, Children’s Hospital of Philadelphia, Philadelphia, PA, USA; 4The Hemophilia Center, Oregon Health & Science University, Portland, OR, USA; 5Department of Pediatric Hematology and Oncology, University of Kentucky Medical Center, Lexington, KY, USA; 6Department of Hematology/Oncology, Children’s Mercy Hospital, Kansas City, MO, USA; 7Hemophilia Treatment Center, Nationwide Children’s Hospital and The Ohio State University College of Medicine, Columbus, OH, USA; 8Takeda Development Center Americas, Inc, Lexington, MA, USA; 9Outcomes Research & Epidemiology, Takeda Pharmaceuticals International AG, Zurich, SwitzerlandCorrespondence: Maureen WattTakeda Pharmaceuticals International AG, Thurgauerstrasse 130, Glattpark-Opfikon, Zurich, 8152, SwitzerlandTel [phone]Fax [phone]Email [email protected]: 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: hemophilia A, recombinant factor VIII, physical activity, post-authorization study, prophylaxis, bleeding

Keywords

• hemophilia a
• recombinant factor viii
• physical activity
• post-authorization study
• prophylaxis
• bleeding