Successful second ITI with factor IX and combined immunosuppressive therapy

Summary

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, de-xamethasone, 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 immunosup-pressants, which were initiated one week before high-dose FIX. No allergic reactions, nephrotic syndrome or serious infection occurred during ITI. The FIX inhibitor was unde-tectable after five weeks of treatment and remained so until 19 months of follow-up.

Zusammenfassung

Im Vergleich zu Inhibitorpatienten mit Hämo-philie A führt die Immuntoleranzinduktion (ITI) bei Patienten mit Hämophilie B und Inhibitor seltener zum Erfolg und häufiger zu Kompli-kationen wie allergischen Reaktionen oder nephrotischem Syndrom. Nach Fallberichten scheint die zusätzliche Immunsuppression vielversprechend.

Wir berichten über einen 18-jährigen Patien-ten mit schwerer Hämophilie B und einem Faktor IX (FIX)-Inhibitor von maximal 2,6 Be-thesda-Einheiten sowie allergischer Hautre-aktion auf FIX-Infusion. Bereits im Alter von 5 Jahren hatte dieser Patient einen FIX-Inhibitor mit allergischer Reaktion auf FIX und ak-tiviertes Prothrombinkomplex-Konzentrat. Im Alter von 11 Jahren führte eine ITI mit hoch-dosiertem FIX, Rituximab, Dexamethason, Mycofenolat-Mofetil (MMF) und intraven-ösen Immunglobulinen zu einer sieben Jahre anhaltenden Remission.

Aktuell wurde eine erneute ITI mit o. g. immun suppressiver Therapie, die eine Woche vor FIX-Gabe begonnen wurde, durchgeführt, ohne dass es erneut zu Allergie, Infektion oder nephrotischem Syndrom kam. Der FIX-Inhibitor war nach fünf Wochen negativ und die Remission anhaltend über den Beobach-tungszeitraum von 19 Monaten.

Keywords

Haemophilia B inhibitors - immune tolerance induction - immunosuppression

Schlüsselwörter

Hämophilie B - Inhibitor - Immuntoleranz -induktion - Immunsuppression

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