title: Experience of Advate rAHF-PFM in previously untreated patients and minimally treated patients with haemophilia A.
abstract: We report a prospective trial of 55 previously untreated patients (PUPs) and minimally treated patients (MTPs) with severe/moderately severe haemophilia A (baseline factor VIII [FVIII] ≤2%) treated with a single FVIII replacement product. It was the objective of this study to evaluate the immunogenicity, efficacy, and safety of rAHF-PFM (Advate®). On-demand or prophylactic treatment regimens were determined at the discretion of the investigator. rAHF-PFM was also permitted for perioperative management. There were 633 bleeding episodes (BEs), including 517 treated, and 466 rated for efficacy. Haemostatic efficacy was considered excellent/good in 93% of 466 rated treatments. Of 517 treated BEs, 463/517 (90%) were managed with one (356/517 [69%]) or two infusions (107/517 [21%]). There were 27 surgeries. Intraoperative (n=22) and postoperative (n=25) haemostatic efficacies were considered excellent or good in 100% of rated surgeries. Related serious adverse events (SAEs) were inhibitor development in 16/55 (29.1%) subjects who received at least one infusion of rAHF-PFM. Non-serious, related adverse events (AEs) were few in number (14 in eight subjects). The odds ratio (OR [95% Confidence Interval, CI]) of developing inhibitors was significantly higher in subjects with a family history of inhibitor (4.95[1.29-19.06]), non-Caucasian ethnicity (4.18, [1.18-14.82]), and intensive treatment at high dose (4.5 [1.05-19.25]) within ≤20 exposure days (EDs). In conclusion, rAHF-PFM was safe and effective for the management and perioperative coverage of PUPs/MTPs with severe/moderately severe haemophilia A. This report supports previous findings from studies in which family history of inhibitor, non-Caucasian ethnicity, and high intensity treatment were associated with high risk of inhibitor development.
authors.affiliation: Prof.-Hess-Kinderklinik, Klinikum Bremen-Mitte, St.-Juergen Str. 1, 28177 Bremen, Germany. guenterauerswald@aol.com
authors.forename: Guenter
authors.initials: G
authors.lastname: Auerswald
authors.forename: Alexis A
authors.initials: AA
authors.lastname: Thompson
authors.forename: Michael
authors.initials: M
authors.lastname: Recht
authors.forename: Deborah
authors.initials: D
authors.lastname: Brown
authors.forename: Raina
authors.initials: R
authors.lastname: Liesner
authors.forename: Norma
authors.initials: N
authors.lastname: Guzmán-Becerra
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Dyck-Jones
authors.forename: Bruce
authors.initials: B
authors.lastname: Ewenstein
authors.forename: Brigitt
authors.initials: B
authors.lastname: Abbuehl
mesh_terms: D000906:Antibodies / Q000097:blood; D004334:Drug Administration Schedule; D005006:Ethnicity; D005060:Europe / Q000453:epidemiology; D005169:Factor VIII / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D005260:Female; D006467:Hemophilia A / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000208:ethnology; D006470:Hemorrhage / Q000097:blood / Q000188:drug therapy* / Q000208:ethnology / Q000209:etiology; D006487:Hemostasis / Q000187:drug effects*; D006490:Hemostatics / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D016014:Linear Models; D016015:Logistic Models; D008297:Male; D009656:North America / Q000453:epidemiology; D016017:Odds Ratio; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000906:Antibodies; D006490:Hemostatics; D005169:Factor VIII