NecLip-pdFVIII

The last 15 years have seen new extended half‐life (EHL) recombinant FVIII/IX concentrates and nonreplacement therapy for haemophilia A (emicizumab) introduced in Europe. These changes affect FVIII/IX exposure in previously untreated patients (PUPs) and previously treated patients (PTPs) with severe haemophilia A and B (SHA and SHB) and may modify inhibitor development and/or detection.

To report trends in treatment for severe haemophilia and concomitant changes in inhibitor incidence.

Between 2008 and 2022, 97 centres reported inhibitor development against FVIII/IX concentrates to the European Haemophilia Safety Surveillance System (EUHASS). Inhibitors were reported quarterly, and PUPs without inhibitor development annually. Cumulative inhibitor incidences (95% confidence intervals [CI]) were calculated for PUPs and incidence rates/1000 years (CI) for PTPs.

By 2022, SHA‐PUPs ( n  = 1574) received emicizumab (44%), SHL‐rFVIII (21.5%), pdFVIII (17.5%) and EHL‐rFVIII (17%). SHB‐PUPs ( n  = 236) received EHL‐rFIX (79%) and SHL‐rFIX (21%). SHA‐PTPs (68,772 years) received EHL‐rFVIII (31%), SHL‐rFVIII (28%), emicizumab (25%), and pdFVIII (15%). SHB PTPs (11,185 years) received EHL‐rFIX (69%), pdFIX (15%) and SHL‐rFIX (15%). Observed Inhibitor incidence in SHA‐PUPs decreased from 24% before 2016 to 6% in 2022 ( p < 0.001), and potentially in SHB‐PUPs too (from 9% to 3%; p  = 0.066), but remained stable in SHA/SHB PTPs.

In 2022, 44% of SHA‐PUPs and 25% of SHA‐PTPs received emicizumab prophylaxis. Concomitantly, observed inhibitor incidence reduced to 6% in SHA‐PUPs. In SHB, EHL‐rFIX treatment increased to 79% in SHB‐PUPs and 69% in SHB‐PTPs. Assessing inhibitor incidence for new concentrates is likely to be hampered by novel treatments causing delayed exposure to FVIII/FIX.

This real-world analysis described the Hemophilia A (HA) population in Italy, evaluating drug utilization and consumption of factor VIII (FVIII) products of patients under prophylaxis and on-demand therapy.

From Jan-2017 to Jun-2022, male patients with HA were identified through prescriptions of FVIII products [extended half-life FVIII, standard half-life recombinant FVIII, and plasma-derived FVIII (EHL FVIII, SHL rFVIII, and pdFVIII, respectively)], or emicizumab or FVIII plus von Willebrand factor or HA-related hospitalization using administrative flows of Italian healthcare entities. Patients on treatment with FVIII products during 2021–2022 were stratified by treatment regimen (prophylaxis/on-demand). The mean annual consumption expressed in International Units (IU) of EHL FVIII and SHL FVIII in patients treated during 2021–2022 having at least 12-month follow-up were assessed.

Among included HA patients, 145 (39.5%) received EHL FVIII and 222 (60.5%) SHL FVIII. Of 165 patients on prophylaxis, 105 (64%) received an EHL FVIII and 60 (36%) an SHL FVIII. The mean annual consumption of FVIII was 336,700 IU (median 319,000 IU) for EHL FVIII and 440,267 IU (median 360,500 IU) for SHL FVIII. Specifically, for patients on EHL FVIII, the most common drugs were efmoroctocog alfa (N = 51) and damoctocog alfa pegol (N = 50), followed by turoctocog alfa pegol (N = 25) and rurioctocog alfa pegol (N = 19). Of 702 HA patients initially treated with FVIII products, 74 (10.5%) switched to emicizumab during follow-up.

These findings revealed an extensive use of EHL FVIII products, suggesting growing efforts from clinicians to optimize prophylactic strategies and achieve better bleeding protection.