title: Postauthorization safety surveillance of ADVATE [antihaemophilic factor (recombinant), plasma/albumin-free method] demonstrates efficacy, safety and low-risk for immunogenicity in routine clinical practice.
abstract: Postauthorization safety surveillance of factor VIII (FVIII) concentrates is essential for assessing rare adverse event incidence. We determined safety and efficacy of ADVATE [antihaemophilic factor (recombinant), plasma/albumin-free method, (rAHF-PFM)] during routine clinical practice. Subjects with differing haemophilia A severities and medical histories were monitored during 12 months of prophylactic and/or on-demand therapy. Among 408 evaluable subjects, 386 (95%) received excellent/good efficacy ratings for all on-demand assessments; the corresponding number for subjects with previous FVIII inhibitors was 36/41 (88%). Among 276 evaluable subjects receiving prophylaxis continuously in the study, 255 (92%) had excellent/good ratings for all prophylactic assessments; the corresponding number for subjects with previous FVIII inhibitors was 41/46 (89%). Efficacy of surgical prophylaxis was excellent/good in 16/16 evaluable procedures. Among previously treated patients (PTPs) with >50 exposure days (EDs) and FVIII≤2%, three (0.75%) developed low-titre inhibitors. Two of these subjects had a positive inhibitor history; thus, the incidence of de novo inhibitor formation in PTPs with FVIII≤2% and no inhibitor history was 1/348 (0.29%; 95% CI, 0.01-1.59%). A PTP with moderate haemophilia developed a low-titre inhibitor. High-titre inhibitors were reported in a PTP with mild disease (following surgery), a previously untreated patient (PUP) with moderate disease (following surgery) and a PUP with severe disease. The favourable benefit/risk profile of rAHF-PFM previously documented in prospective clinical trials has been extended to include a broader range of haemophilia patients, many of whom would have been ineligible for registration studies.
authors.affiliation: Institute of Experimental Haematology and Transfusion Medicine, University Clinic Bonn, Bonn, Germany. johannes.oldenburg@ukb.uni-bonn.de
authors.forename: J
authors.initials: J
authors.lastname: Oldenburg
authors.forename: J
authors.initials: J
authors.lastname: Goudemand
authors.forename: L
authors.initials: L
authors.lastname: Valentino
authors.forename: M
authors.initials: M
authors.lastname: Richards
authors.forename: H
authors.initials: H
authors.lastname: Luu
authors.forename: A
authors.initials: A
authors.lastname: Kriukov
authors.forename: H
authors.initials: H
authors.lastname: Gajek
authors.forename: G
authors.initials: G
authors.lastname: Spotts
authors.forename: B
authors.initials: B
authors.lastname: Ewenstein
mesh_terms: D000293:Adolescent; D000328:Adult; D019774:Blood Coagulation Factor Inhibitors / Q000032:analysis*; D002648:Child; D002675:Child, Preschool; D005169:Factor VIII / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006467:Hemophilia A / Q000097:blood / Q000188:drug therapy*; D006470:Hemorrhage / Q000517:prevention & control; D006801:Humans; D008297:Male; D008875:Middle Aged; D011358:Product Surveillance, Postmarketing; D011994:Recombinant Proteins; D014481:United States
chemical_list: D019774:Blood Coagulation Factor Inhibitors; D011994:Recombinant Proteins; C078147:F8 protein, human; D005169:Factor VIII