title: Prospective surveillance study of haemophilia A patients switching from moroctocog alfa or other factor VIII products to moroctocog alfa albumin-free cell culture (AF-CC) in usual care settings.
abstract: This prospective, open-label, postauthorisation safety surveillance study assessed clinically significant inhibitor development in patients with severe haemophilia A transitioning from moroctocog alfa or other factor VIII (FVIII) replacement products to reformulated moroctocog alfa (AF-CC). Males aged ≥ 12 years with severe haemophilia A (FVIII:C) < 1 IU/dl), > 150 exposure days (EDs) to recombinant or plasma-derived FVIII products, and no detectable inhibitor at screening were enrolled. Primary end point was the incidence of clinically significant FVIII inhibitor development. Secondary end points included annualised bleeding rate (ABR), less-than-expected therapeutic effect (LETE), and FVIII recovery. Patients were assigned to one of two cohorts based on whether they were transitioning to moroctocog alfa (AF-CC) from moroctocog alfa (cohort 1; n=146) or from another recombinant or plasma-derived FVIII product (cohort 2; n=62). Mean number of EDs on study was 94 (range, 1-139). Six positive FVIII inhibitor results, as determined by local laboratories, were reported in four patients; none were confirmed by a central laboratory, no inhibitor-related clinical manifestations were reported, and all anti-FVIII antibody assays were negative. Median ABRs were 23.4 and 3.4 in patients categorised at baseline as following on-demand and prophylactic regimens, respectively; 86.5% of bleeding episodes resolved after one infusion. LETE incidence was 0.06% and 0.19% in the on-demand and prophylaxis settings, respectively. FVIII recovery remained constant throughout the study. No new safety concerns were identified. This study found no increased risk of clinically significant FVIII inhibitor development in patients transitioning from moroctocog alfa or other FVIII replacement products to moroctocog alfa (AF-CC).
authors: Rafael Parra Lopez, MD, University Hospital Valle d'Hebrón, Department of Hemophilia, Passeig de la Vall d'Hebrón, s/n, 08035 Barcelona, Catalonia, Spain, Tel.: +34 93 274 60 00, Fax: +34 93 274 90 27, E-mail: rparra@vhebron.net.
authors: Rafael
authors: R
authors: Parra Lopez
authors: Laszlo
authors: L
authors: Nemes
authors: Victor
authors: V
authors: Jimenez-Yuste
authors: Luminita
authors: L
authors: Rusen
authors: Ana R
authors: AR
authors: Cid
authors: Robert J
authors: RJ
authors: Charnigo
authors: James A
authors: JA
authors: Baumann
authors: Lynne
authors: L
authors: Smith
authors: Joan M
authors: JM
authors: Korth-Bradley
authors: Pablo
authors: P
authors: Rendo
mesh_terms: D000293:Adolescent; D000328:Adult; D001323:Autoantibodies / Q000097:blood; D015415:Biomarkers / Q000097:blood; D001780:Blood Coagulation Tests; D002648:Child; D003029:Coagulants / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology / Q000493:pharmacokinetics; D057915:Drug Substitution; D005169:Factor VIII / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology / Q000493:pharmacokinetics; D006467:Hemophilia A / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D008297:Male; D008875:Middle Aged; D011358:Product Surveillance, Postmarketing; D011446:Prospective Studies; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D015415:Biomarkers; D003029:Coagulants; C427184:recombinant factor VIII SQ; C078147:F8 protein, human; D005169:Factor VIII
keywords: Haemophilia A; blood coagulation factor inhibitors; factor VIII; moroctocog alfa; safety; surveillance