Eradication of FIX inhibitor in haemophilia B children using low‐dose immune tolerance induction with rituximab‐based immunosuppressive agent(s) in China

Abstract

Introduction: Development of haemophilia B inhibitors (HBI) results in the ineffectiveness of FIX replacement therapy. Inhibitor eradication by immune tolerance induction (ITI) is therefore necessary. In HBI, ITI even at high FIX dose is less effective and has a higher risk of severe complications. Aim: To characterize clinical features and outcome of ITI on HBI. Methods: This retrospective study was conducted in Haemophilia Paediatric Comprehensive Care Centre of China. We used low-dose ITI (25-50 FIX IU/kg/three-timesweekly to every-other-day) with domestic prothrombin complex concentrate (PCC), combined with two successive immunosuppressive (IS) regimens.Results: Sixteen HBI children, representing 5.7% of all and 14.4% of our severe registered HB patients, were enroled. Seven cases reported allergic reactions (ARs) proximal to inhibitor development. The historic peak inhibitor titre was median 54.2 (range 4.7-512) BU, and 15 (93.8%) had high-titre inhibitors. Twelve patients adherent to ITI were analysable. Of the nine ITI patients who received rituximab/prednisone (IS Regimen-1), four achieved tolerization in 1.4-43.3 months. Two subsequently relapsed but re-tolerized after a second course of IS Regimen-1. During ITI, the median treated bleed was .39/month (82.7% reduction from before ITI), and the incidence of AR and nephrotic syndrome (NS) complications was each at 22% (2/9). Three ITI patients

Factor IX inhibitors in haemophilia B: A report of National Haemophilia Registry in China

“…Nonetheless, our observations suggested that ITI therapy to eradicate FIX inhibitor was still feasible even with low-dose ITI more affordable to patients in regions of economic constraint like China. A recent paper by Li et al 32 reported FIX inhibitor eradication in 16 Chinese HB inhibitor boys in their centre, which had nine overlaps with our patients on ITI therapy in our study. Consistent with our conclusion, they also suggested that inhibitor eradication could be achieved by low-dose ITI protocol using PCC, probably in combination with immunomodulation agents.…”

“…Nonetheless, our observations suggested that ITI therapy to eradicate FIX inhibitor was still feasible even with low‐dose ITI more affordable to patients in regions of economic constraint like China. A recent paper by Li et al 32 . reported FIX inhibitor eradication in 16 Chinese HB inhibitor boys in their centre, which had nine overlaps with our patients on ITI therapy in our study.…”

Hemophilia throughout the life cycle

“…For hemophilia B patients with inhibitors and an allergic reaction/anaphylaxis to factor IX therapy, it is recommended to treat acute bleeds with rFVIIa but is against the use of aPCC as it contains FIX and may cause or worsen an allergic reaction 3 . Also for hemophilia B, the association of ITI protocols with immunosuppressive regimens is an option to achieve the eradication of inhibitors 53,54 .…”