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-times-weekly 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 received modified 'Beutel' protocol (IS Regimen-2) using multiple-IS-drugs, and two had rapid tolerization (.8 and 1.8 months).
Conclusions: Inhibitor eradication could be achieved by low-dose ITI protocol using PCC combined with IS. Larger studies are needed to confirm if ITI with IS Regimen-2 is more effective with less complications.
Keywords: FIX inhibitor; haemophilia B; immune tolerance induction; immunosuppressive agents; low-dose.
© 2022 John Wiley & Sons Ltd.