Prompt immune tolerance induction at inhibitor diagnosis regardless of titre may increase overall success in haemophilia A complicated by inhibitors: experience of two US centres

作者：Nakar C^*; Manco Johnson M J; Lail A; Donfield S; Maahs J; Chong Y; Blades T; Shapiro A

来源：Haemophilia, 2015, 21(3): 365-373.

DOI：10.1111/hae.12608

• factor VIII
• haemophilia A
• immune tolerance induction
• inhibitors
• time interval
• titre

Current guidelines recommend delaying thestart of immune tolerance induction (ITI) until theinhibitor titre is <10 Bethesda units (BU) to improve success. This study was conducted to evaluate ITI outcome relativeto time to start ITI from inhibitor detection irrespective of inhibitor titre. Data were retrospectively collected from two US haemophilia treatment centres (HTCs) on subjects with severe/moderate factor VIII (FVIII) deficiency with inhibitors who underwent ITI. Outcomes were defined pragmatically: success - negative inhibitor titre and ability to use FVIII concentrate for treatment/bleed prevention; partial success - inhibitor titre 1 to <5 BU with ability to use FVIII concentrate for treatment of bleeding; failure - ITI ongoing >3 years without achieving success/partial success, or ITI discontinuation. Fifty-eight subjects were included; 32 of 39 (82%) with high-responding inhibitor (HRI) achieved success, 7 failed. HRI subjects were subdivided based on ITI start time: 23/39 subjects started within 1month of detection and 22/23 (96%) achieved success. Of these 23, 13 started ITI with an inhibitor titre >= 10 BU; all were successes. Eleven of 39 HRI subjects had an interval >6 months until ITI start; 7 (64%) achieved success. Time from inhibitor detection to ITI start may play a critical role in outcome. A titre >= 10 BU atITIstart did not influence outcome in subjects when ITI was initiated within 1month of detection. Prompt ITI should be considered a viable therapeutic option in newly identified patients with inhibitors regardless of current inhibitor titre.

• 出版日期2015-5