Long-term clinical and economic outcomes in previously untreated paediatric patients with severe haemophilia A: A nationwide real-world study with 700 person-years.

Abstract

For previously untreated patients (PUPs) with severe haemophilia A in Finland for the past 2 decades, the standard practice has been to start early primary prophylaxis. We evaluated the long-term clinical outcomes and costs of treatment with high-dose prophylaxis in PUPs from birth to adolescence, including immune tolerance induction (ITI). From the medical records of all PUPs born between June 1994 and May 2013 in Finland, we retrospectively extracted data on clinical outcomes and healthcare use. Using linear mixed models, we analysed longitudinal clinical outcome data. To analyse skewed cost data, including zero costs, we applied hurdle regression. All 62 patients received early regular prophylaxis; totally, they have had treatment for nearly 700 patient-years. The median age of starting home treatment was 1.1years. The mean (SD) annual treatment costs (€perkg) were 4391€ (3852). For ages 1-3, ITI comprised over half of the costs; in other groups, prophylactic FVIII treatment dominated. With these high costs, however, clinical outcomes were desirable; median (IQR) ABR was low at 0.19 (0.07-0.46) and so was AJBR at 0.06 (0-0.24). Thirteen (21%) patients developed a clinically significant inhibitor, 10 (16%) with a high titre. All ITIs were successful. The mean costs for ITI were 383448€ (259085). The expected ITI payback period was 1.81 (95% CI 0.62-12.12) years. Early high-dose prophylaxis leads to excellent long-term clinical outcomes, and early childhood ITI therapy seems to turn cost-neutral generally already in 2years.