Hemophilia prophylaxis adherence and bleeding using a tailored, frequency-escalated approach: The Canadian Hemophilia Primary Prophylaxis Study

Authors: Dover, S., Blanchette, V. S., Wrathall, D., Pullenayegum, E., Kazandjian, D., Song, B., Hawes, S. A., Cloutier, S., Rivard, G. E., Klaassen, R. J., Paradis, E., Laferriere, N., Stain, A. M., Chan, A. K., Israels, S. J., Sinha, R., Steele, M., Wu, J. K. M., and Feldman, B. M.

Publication: Research and Practice in Thrombosis and Haemostasis; 4,2:318-325. March 2020

Affiliations: Child Health Evaluative Sciences The Hospital for Sick Children Toronto ON Canada; Division of Hematology/Oncology The Hospital for Sick Children Toronto ON Canada; Department of Pediatrics Faculty of Medicine University of Toronto Toronto ON Canada; Institute of Health Policy, Management and Evaluation the Dalla Lana School of Public Health University of Toronto Toronto ON Canada; Division of Pediatric Hematology/Oncology IWK Health Centre Halifax NS Canada; Centre de l’hemophilie de l’est du Quebec Hopital de l’Enfant-Jesus Universite Laval Quebec QC Canada; Division of Pediatric Hematology/Oncology Children’s Hospital of Eastern Ontario University of Ottawa Ottawa ON Canada; Health Sciences North Sudbury ON Canada.

Abstract: BACKGROUND: Standard of care for persons with severe hemophilia A includes regular replacement of factor VIII (FVIII). Prophylaxis regimens using standard half-life (SHL) FVIII concentrates, while effective, are costly and require frequent intravenous infusions. AIM: This study evaluated the adherence of 56 boys with severe hemophilia A to tailored, frequency-escalated prophylaxis with an SHL recombinant FVIII concentrate. METHODS: We reviewed the factor infusion and bleeding logs of study subjects. Adherence to the prescribed regimen was calculated on a weekly basis, and bleeding rates were determined from self/proxy-reported bleeding logs. The primary outcome was adherence to the prescribed prophylaxis regimen. RESULTS: The median (range of values [ROV]) weekly adherence to prophylaxis was 85.7% (37.4%-99.8%). The median (ROV) adherent weeks on steps 1 (weekly), 2 (twice weekly), and 3 (alternate-day) were 92.9% (50%-100%), 80.3 (32%-96%), and 72.6% (14%-98%); relative to step 1, subjects were less likely to be adherent on steps 2 and 3 (P < 0.00). On step 1, our cohort had higher adherence than previously reported rates. The median (ROV) adherence to the breakthrough bleeding protocol was 47.1% (0%-100%). At any given time, bleeding risk was reduced by 15% for each 10% increase in adherence during the preceding 12 weeks (hazard ratio, 0.85; 95% confidence interval, 0.81-0.90). CONCLUSION: This cohort had high rates of adherence to the prescribed prophylaxis regimen. Initiating prophylaxis with once-weekly infusions facilitated adherence to the prophylaxis regimen in this cohort of boys with severe hemophilia A started on primary prophylaxis at a very young age.