Postauthorization safety surveillance of ADVATE [antihaemophilic factor (recombinant), plasma/albumin‐free method] demonstrates efficacy, safety and low‐risk for immunogenicity in routine clinical practice

Summary.  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.