Abstract Number: OC 55.4
Meeting: ISTH 2021 Congress
Theme: Hemophilia and Rare Bleeding Disorders » Hemophilia - Clinical
Background: The development of neutralizing anti-factor VIII antibodies (inhibitors) is the main complication in hemophilia A (HA) patients. Among non-genetic risk factors for inhibitor development, the type of factor VIII concentrate used in replacement therapy (recombinant or plasma-derived) remains controversial.
Aims: To compare the incidence of inhibitor development between previously untreated patients (PUPs) with severe or moderately severe HA treated with a third-generation recombinant factor VIII (rFVIII) or plasma-derived factor VIII (pdFVIII) (multiple brands) concentrates for the first 50 exposure days (EDs).
Methods: This is an open-label, multicenter, prospective/retrospective, uncontrolled study conducted in eleven hemophilia centers from Brazil. The inclusion criteria were (a)endogenous factor VIII <2IU/dL and (b)exclusive treatment with rFVIII or pdFVIII until 50EDs or inhibitor development. Positive inhibitor was defined as at least two plasma samples with Bethesda-Nijmegen assay results ≥0.6BU/mL. Patients were considered as having low-titer inhibitors when peak titers were <5BU/mL, and high-titer inhibitors if ≥5BU/mL on at least one occasion. This study was approved by the local Ethics Committee. Written informed consent was collected for all patients.
Results: Of 283 eligible patients, 271 were analyzed. 96(35.4%) were treated with pdFVIII, and 175 (64.6%) received rFVIII (Table 1). Inhibitors developed in 93 of the 271 patients (cumulative incidence, 34.3%); 70 of whom had high-titer (25.8%). Twenty-nine of 96 (30.2%) patients treated with pdFVIII developed inhibitors, with 21 (21.9%) developing high-titer inhibitors. Sixty-four of 175 (36.6%) patients treated with rFVIII developed inhibitors, with 49 (28%) developing high-titer inhibitors (Fig.1). The use of rFVIII resulted in similar inhibitor development risk when compared with pdFVIII for both all inhibitors (P=0.22; adjusted hazard ratio [HR], 1.3; 95% confidence interval [CI], 0.86 to 1.20) and high-titer inhibitors (P=0.20; HR, 1.39; 95% CI, 0.85 to 2.25).
| Table 1 – Patients’ characteristics according to the factor VIII product received. | ||
| Characteristics | rFVIII (N = 175) |
pd-FVIII (N = 96) |
| Median age (months) at first exposure to factor VIII (range) | 12 (0-112) | 12 (0-93) |
| Non-Caucasian N (%) | 89 (50.9) | 35 (36.5) |
| Endogenous factor VIII < 1 IU/dL N (%) | 164 (93.7) | 95 (98.9) |
| Type of inhibitor N (%) All inhibitors Low titer inhibitor High-titer inhibitor |
64 (36.6) 15 (8.6) 49 (28) |
29 (30.2) 8 (8.3) 21 (21.9) |
| Median exposure days at inhibitor development (range) All inhibitors Low titer inhibitor High-titer inhibitor |
17 (4-50) 15 (5-50) 18 (4-50) |
20 (5-50) 32 (14-50) 18 (5-50) |
| Median peak of inhibitor titer Bethesda units/ml (range) All inhibitors Low titer inhibitor High-titer inhibitor |
28 (1.9-704) 2.9 (1.9-3.6) 35 (5.8-704) |
10.8 (1.6-388) 2.7 (1.6-4.4) 21.6 (6-388) |
Patients’ characteristics according to the factor VIII product received.
Cumulative incidence of inhibitors according to factor VIII product received within 50 exposure days. Kaplan-Meier curves for all inhibitors (A) and high-titer inhibitors (B) cumulative incidence over time, which is counted as exposure days. N, number of patients; rFVIII, recombinant factor VIII concentrate; pdFVIII, plasma-derived factor VIII concentrate.
Conclusions: No difference in inhibitor development was observed between using a third-generation rFVIII, and pdFVIII concentrates in HA PUPs from Brazil.
To cite this abstract in AMA style:
Prezotti ANL, Rocha DMdC, Renni M, Cerqueira MH, Ferreira C, Pinto ISS, Roberti MdR, Ribeiro R, Villaça PR, Okazaki E, Orletti MdPSV, Medina S, Lorenzato C, de Oliveira LO, Leite ALM, Pinto CMSP, Antunes SV, L Montalvão SA, G Yamaguti-Hayakawa G, C Ozelo M. No Difference in Inhibitor Incidence in Previously Untreated Patients (PUPs) with Severe and Moderately Severe Hemophilia A Treated with a Third-generation Recombinant Factor VIII when Compared with Plasma-derived Factor VIII [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/no-difference-in-inhibitor-incidence-in-previously-untreated-patients-pups-with-severe-and-moderately-severe-hemophilia-a-treated-with-a-third-generation-recombinant-factor-viii-when-compared-with-p/. Accessed December 11, 2023.« Back to ISTH 2021 Congress
ISTH Congress Abstracts - https://abstracts.isth.org/abstract/no-difference-in-inhibitor-incidence-in-previously-untreated-patients-pups-with-severe-and-moderately-severe-hemophilia-a-treated-with-a-third-generation-recombinant-factor-viii-when-compared-with-p/