Effect of von Willebrand factor on inhibitor eradication in patients with severe haemophilia A: a systematic review.
This systematic review was designed to summarize the reported valid quantitative evidence on the association between use of von Willebrand factor (VWF)-containing Factor VIII (FVIII) concentrates and successful immune tolerance induction (ITI) in patients with severe haemophilia A. The primary outcome was successful ITI; secondary outcomes were time to success, complications of the inhibitor or ITI and relapse of the inhibitor. A systematic literature search identified 26 randomized controlled trials, registries and cohort studies, evaluating a total of 1284 patients. For a pooled meta-analysis, 13 studies evaluating 382 patients were included. Due to incomplete data we were not able to assign pre-ITI risk categories to all patients for risk factor analysis. The meta-analysis did not demonstrate a difference in the proportion of patients with successful inhibitor eradication between those treated with VWF-containing products and those treated with FVIII concentrates devoid of VWF (relative risk [RR] 0·70 (95% confidence interval [CI] 0·52-0·89) and 0·84 (95% CI 0·75-0·93) respectively). Bleeding rate during ITI ranged from 0·00 to 0·85 bleeding episodes per year. The proportion of patients with a relapse of the inhibitor (range 0-20%) was mentioned in four studies that were included in the meta-analysis. The results of this systematic review do not support the idea of a positive effect of VWF-containing products in ITI.
Department of Pediatric Haematology, Emma Children's Hospital, Academic Medical Center, Amsterdam, The Netherlands.
Alice S
AS
van Velzen
Marjolein
M
Peters
Johanna G
JG
van der Bom
Karin
K
Fijnvandraat
D000906:Antibodies / Q000276:immunology; D006467:Hemophilia A / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance / Q000187:drug effects*; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome; D014841:von Willebrand Factor / Q000276:immunology / Q000627:therapeutic use*
D000906:Antibodies; D014841:von Willebrand Factor
VWF; antibodies; haemophilia A; human factor VIII protein; immunology