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First prospective report on immune tolerance in poor risk haemophilia A inhibitor patients with a single factor VIII/von Willebrand factor concentrate in an observational immune tolerance induction study
Author(s) -
Kreuz W.,
Escuriola Ettingshausen C.,
Vdovin V.,
Zozulya N.,
Plyushch O.,
Svirin P.,
Andreeva T.,
Bubanská E.,
Campos M.,
BenedikDolničar M.,
JiménezYuste V.,
Kitanovski L.,
Klukowska A.,
Momot A.,
Osmulskaya N.,
Prieto M.,
Šalek S. Z.,
Velasco F.,
Pavlova A.,
Oldenburg J.,
Knaub S.,
Jansen M.,
Belyanskaya L.,
Walter O.
Publication year - 2016
Publication title -
haemophilia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.213
H-Index - 92
eISSN - 1365-2516
pISSN - 1351-8216
DOI - 10.1111/hae.12774
Subject(s) - medicine , haemophilia a , haemophilia , von willebrand factor , immune tolerance , interim analysis , observational study , titer , prospective cohort study , gastroenterology , surgery , immune system , immunology , clinical trial , antibody , platelet
/background Development of neutralizing inhibitors against factor VIII (FVIII) is a major complication of haemophilia A treatment. Aim The ongoing, international, open‐label, uncontrolled, observational immune tolerance induction (ObsITI) study evaluates ITI , the standard of care in patients with inhibitors. Patients/methods Forty‐eight prospective patients in this interim analysis received a single plasma‐derived, von Willebrand factor‐stabilized, FVIII concentrate (pdFVIII/VWF) for ITI . According to recommended Bonn protocol, ‘low responders’ at ITI start (<5 BU) received 50–100 IU FVIII kg −1 daily, or every other day; ‘high responders’ (≥5 BU) received 100 IU FVIII kg −1 every 12 h. Results Forty of 48 patients (83.3%), had at least one risk factor for poor ITI ‐prognosis at ITI start (i.e. age ≥7 years, >2 years since inhibitor diagnosis, inhibitor titre ≥10 BU at the start of ITI , or prior ITI failure). Nonetheless, 34 patients (70.8%) achieved complete success , 3 (6.3%) partial success , 1 (2.1%) partial response ; ITI failed in 10 patients (20.8%), all with poor prognosis factors. All six low responders achieved complete success . ITI outcome was significantly associated with inhibitor titre level at ITI start ( P = 0.0068), number of poor prognosis factors for ITI success ( P = 0.0187), monthly bleeding rate during ITI ( P = 0.0005) and peak inhibitor titre during ITI ( P = 0.0007). Twenty‐two of 35 high responder patients (62.9%) with ≥1 poor prognosis factor achieved complete success . Conclusion Treatment with a single pdFVIII/VWF concentrate, mainly according to the Bonn protocol, resulted in a high ITI success rate in haemophilia A patients with inhibitors and poor prognosis for ITI success.