Optimising prophylaxis outcomes and costs in haemophilia patients switching to recombinant FVIII-Fc: a single-centre real-world experience

Abstract

Background. The recombinant factor VIII (rFVIII)-IgG1 Fc fusion protein (rFVIII-Fc) was the first available extended half-life rFVIII, shown to prolong dosing intervals of individualised prophylaxis in patients with severe haemophilia A, maintaining low bleeding rates and unchanged or lower FVIII dose versus standard half-life (SHL) rFVIII. Few data are available about real-world experience with rFVIII-Fc, including criteria for patient switching from SHL products, follow up and prophylaxis optimisation.
Materials and methods. A single-centre retrospective study was designed to review patients switched to rFVIII-Fc, based on individual needs, after pharmacokinetic (PK) assessment, according to routine clinical practice. In patients with adequate post-switch follow up, data about rFVIII-Fc prophylaxis were compared with those from the last 18-months SHL rFVIII prophylaxis.
Results. Of 25 candidates, 18 patients (15 severe, 3 moderate; aged 9-62 years; 3 with inhibitor history) started rFVIII-Fc regimens, with comparable FVIII weekly dose and reduced infusion frequency (mean −30%) in all 17 patients previously on SHL rFVIII prophylaxis thrice weekly or every other day. Over a mean 18-month follow up in 13 patients, compared with SHL products, further reduced infusion frequency (mean −40%; p<0.001; interval ≥4 days in 9 patients), improved treatment satisfaction (Hemo-sat questionnaires), significantly lower FVIII weekly dose and annual consumption (mean −12%; p=0.019), comparable bleeding rates and FVIII trough levels, and improved management of breakthrough bleeding were observed. von Willebrand Factor Antigen (VWF:Ag) correlated to PK variables and both had relationships with rFVIII-Fc weekly dose, increasing statistical significance over the follow-up period. No inhibitors or drug-related adverse events were recorded.
Discussion. In this real-world series of patients, a switch to rFVIII-Fc, based on careful assessment of clinical needs, PK testing and treatment monitoring, was able to optimise individual convenience, efficacy and costs of prophylaxis.