title: Inhibitors in nonsevere haemophilia A: outcome and eradication strategies.
abstract: In nonsevere haemophilia A (HA) patients the presence of an inhibitor may exacerbate the bleeding phenotype dramatically. There are very limited data on the optimal therapeutic approach to eradicate inhibitors in these patients. We aimed to describe inhibitor eradication treatment in a large cohort of unselected nonsevere HA patients with inhibitors. We included 101 inhibitor patients from a source population of 2,709 nonsevere HA patients (factor VIII 2-40 IU/dl), treated in Europe and Australia (median age 37 years, interquartile range (IQR) 15-60; median peak titre 7 BU/ml, IQR 2-30). In the majority of the patients (71 %; 72/101) the inhibitor disappeared; either spontaneously (70 %, 51/73) or after eradication treatment (75 %, 21/28). Eradication treatment strategies varied widely, including both immune tolerance induction and immunosuppression. Sustained success (no inhibitor after rechallenge with factor VIII concentrate after inhibitor disappearance) was achieved in 64 % (30/47) of those patients rechallenged with FVIII concentrate. In high-titre inhibitor patients sustained success was associated with eradication treatment (unadjusted relative risk 2.3, 95 % confidence interval 1.3-4.3), compared to no eradication treatment. In conclusion, in nonsevere HA patients most inhibitors disappear spontaneously. However, in 35 % (25/72) of these patients an anamnestic response still can occur when rechallenged, thus disappearance in these patients does not always equal sustained response. Treatment for those requiring eradication has to be decided case by case, as one single approach is unlikely to be appropriate for all.
authors: Alice S
authors: AS
authors: van Velzen
authors: Corien L
authors: CL
authors: Eckhardt
authors: Daniel P
authors: DP
authors: Hart
authors: Marjolein
authors: M
authors: Peters
authors: Savita
authors: S
authors: Rangarajan
authors: Maria Elisa
authors: ME
authors: Mancuso
authors: Frans J
authors: FJ
authors: Smiers
authors: Kate
authors: K
authors: Khair
authors: Pia
authors: P
authors: Petrini
authors: Victor
authors: V
authors: Jiménez-Yuste
authors: Charles R M
authors: CR
authors: Hay
authors: Johanna G
authors: JG
authors: van der Bom
authors: Thynn T
authors: TT
authors: Yee
authors: K. Fijnvandraat, MD PhD, Emma Children's Hospital, Academic Medical Center, Room number H7-228, PO Box 22660, 1100 DD Amsterdam, The Netherlands, Tel.: +31 20 566 2727, Fax: +31 20 566 9683, E-mail: c. j.fijnvandraat@amc.uva.nl.
authors: Karin
authors: K
authors: Fijnvandraat
mesh_terms: D000293:Adolescent; D000328:Adult; D000906:Antibodies / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D002648:Child; D002675:Child, Preschool; D003888:Desensitization, Immunologic / Q000379:methods*; D005060:Europe; D005169:Factor VIII / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D006467:Hemophilia A / Q000097:blood / Q000175:diagnosis / Q000276:immunology / Q000628:therapy*; D006470:Hemorrhage / Q000097:blood / Q000175:diagnosis / Q000276:immunology / Q000628:therapy*; D006490:Hemostatics / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D006801:Humans; D007108:Immune Tolerance; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008875:Middle Aged; D013021:South Australia; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000906:Antibodies; D015415:Biomarkers; D006490:Hemostatics; D007166:Immunosuppressive Agents; C078147:F8 protein, human; D005169:Factor VIII
keywords: Haemophilia A; eradication treatment; factor VIII inhibitors; immune tolerance induction