Successful second ITI with factor IX and combined immunosuppressive therapy. A patient with severe haemophilia B and recurrence of a factor IX inhibitor

Immune tolerance induction (ITI) in patients with haemophilia B and inhibitors may be complicated by anaphylactic reactions and nephrotic syndrome with lower success rates than in haemophilia A (25% vs. 50-90%). According to case reports, immunosuppressive therapy in addition to high doses of factor IX (FIX) appears to be promising. We report an 18-year-old patient with severe haemophilia B and a FIX inhibitor with a maximum titre of 2.6 Bethesda units and allergic skin reactions to FIX infusions. At 5 years of age, this patient already had a FIX inhibitor with allergic reactions to FIX and activated prothrombin complex concentrate. ITI at 11 years of age with high-dose FIX, dexamethasone, rituximab, mycophenolate mofetil and intravenous immunoglobulins had induced a sustained response until the current presentation. The patient was restarted on the same ITI regimen with aforementioned immunosuppressants, which were initiated one week before high-dose FIX. No allergic reactions, nephrotic syndrome or serious infection occurred during ITI. The FIX inhibitor was undetectable after five weeks of treatment and remained so until 19 months of follow-up.