title: Immune tolerance induction in haemophilia A patients with inhibitors by treatment with recombinant factor VIII: a retrospective non-interventional study.
abstract: Immune tolerance induction (ITI) can overcome inhibitory factor VIII (FVIII) antibodies in haemophilia A patients receiving FVIII replacement therapy. The objective was to evaluate the use of sucrose-formulated, full-length recombinant FVIII (rFVIII-FS) for ITI therapy. Patients (<8 years at ITI start) with severe haemophilia A and a peak inhibitor titre >5 Bethesda units (BU) who underwent ITI with any rFVIII-FS dose for ≥ 9 months (or until success) were eligible for this retrospective study. Efficacy analyses included descriptions of ITI treatment regimens and outcomes; ITI success was determined solely at the discretion of the investigator. Safety analyses included assessment of adverse events. Of 51 enrolled patients, 32 [high dose (≥ 85 IU kg(-1) day(-1)), n = 21; low dose, n = 11] were eligible for analysis. ITI was successful in 69% (22/32) of patients (high dose, 66.7%; low dose, 72.7%) after a median of 1.4 years (range, 0.1-3.6 years). Influencing factors for ITI success were start of ITI <1 year after inhibitor detection and an inhibitor titre <10 BU at ITI start. All patients successfully tolerized with ITI continued to receive rFVIII-FS prophylaxis as maintenance therapy, with no inhibitor recurrence from the end of ITI until study enrolment. Use of rFVIII-FS for ITI was effective and well tolerated; success rates were similar to those in published studies.
authors.affiliation: CHU Sainte-Justine, Montreal, QC, Canada.
authors.forename: G E
authors.initials: GE
authors.lastname: Rivard
authors.forename: C
authors.initials: C
authors.lastname: Rothschild
authors.forename: T
authors.initials: T
authors.lastname: Toll
authors.forename: K
authors.initials: K
authors.lastname: Achilles
mesh_terms: D019774:Blood Coagulation Factor Inhibitors / Q000097:blood*; D002648:Child; D002675:Child, Preschool; D005169:Factor VIII / Q000037:antagonists & inhibitors / Q000276:immunology* / Q000627:therapeutic use; D005500:Follow-Up Studies; D006467:Hemophilia A / Q000188:drug therapy / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance; D007223:Infant; D008297:Male; D012189:Retrospective Studies; D013395:Sucrose / Q000037:antagonists & inhibitors / Q000276:immunology* / Q000627:therapeutic use; D013997:Time Factors
chemical_list: D019774:Blood Coagulation Factor Inhibitors; C438308:recombinant FVIII, sugar formulated; D013395:Sucrose; D005169:Factor VIII