ITI with high-dose FIX and combined immunosuppressive therapy in a patient with severe haemophilia B and inhibitor

Summary

Inhibitor development is a rare but serious event in hemophilia B patients. Management is hampered by the frequent occurrence of allergic reactions to factor IX, low success rates of current inhibitor elimination protocols and the risk of development of nephrotic syndrome. Single cases of immune tolerance induction (ITI) including immunosuppressive agents like mycophenolat mofetil (MMF) or rituximab have been reported. We present a case of successful inhibitor elimination with a combined immune-modulating therapy and high-dose factor IX (FIX). This boy had developed a FIX inhibitor at the age of 5 years and had a history of allergic reactions to FIX and to FEIBA^→. Under on-demand treatment with recombinant activated FVII the inhibitor became undetectable but the boy suffered from multiple joint and muscle bleeds. At the age of 11.5 years ITI was attempted with a combination of rituximab, MMF, dexamethasone, intravenous immunoglobulins and high-dose FIX. The inhibitor did not reappear and FIX half-life normalized. No allergic reaction, no signs of nephrotic syndrome and no serious infections were observed.

Zusammenfassung

Die Hemmkörperentwicklung bei Hämophilie B-Patienten stellt eine seltene, aber schwere Komplikation dar. Die Behandlung wird durch das häufige Auftreten von allergischen Reaktionen auf Faktor IX (FIX), geringe Erfolgsraten der gängigen Eliminations-Protokolle und das Risiko der Entstehung eines nephrotischen Syndroms erschwert. Es existieren einzelne Berichte über Immuntoleranzinduktionen (ITI) mit Immunsuppressiva wie MycophenolatMofetil (MMF) oder Rituximab. Wir berichten über eine erfolgreiche Hemmkörperelimination mit einer kombinierten immun-modulierenden Therapie und hochdosierter FIX-Gabe. Der Junge hatte mit 5 Jahren einen Inhibitor entwickelt und zeigte allergische Reaktionen auf FIX und FEIBA^→. Unter der Bedarfsbehand-lung mit rekombinantem aktiviertem FVII war der Inhibitor nicht messbar, aber der Junge erlitt multiple Gelenk- und Muskelblutungen. Mit 11,5 Jahren wurde eine ITI mit einer Kombination aus Rituximab, MMF, Dexamethason, Immunglobulinen und hochdosiertem FIX begonnen. Der Inhibitor wurde nicht geboostert und die FIX-Halbwertszeit normalisierte sich. Es wurden weder allergische Reaktionen, Zei-chen eines nephrotischen Syndroms oder schwere Infektionen beobachtet.

Keywords

Haemophilia B - inhibitor - immune tolerance induction - immunosuppression

Schlüsselwörter

Hämophilie B - Hemmkörper - Immuntoleranz -induktion - Immunsuppression

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