Kreuz, WEscuriola Ettingshausen, CVdovin, VZozulya, NPlyushch, OSvirin, PAndreeva, TBubanská, ECampos, MBenedik-Dolničar, MJiménez-Yuste, VKitanovski, LKlukowska, AMomot, AOsmulskaya, NPrieto, MŠalek, S ZVelasco, FPavlova, AOldenburg, JKnaub, SJansen, MBelyanskaya, LWalter, OObsITI study groupObsITI committee2023-01-252023-01-252015-07-23http://hdl.handle.net/10668/10016Development of neutralizing inhibitors against factor VIII (FVIII) is a major complication of haemophilia A treatment. The ongoing, international, open-label, uncontrolled, observational immune tolerance induction (ObsITI) study evaluates ITI, the standard of care in patients with inhibitors. 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 ( 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. 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.enAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/Bonn protocolfactor VIII inhibitorsfactor VIII/von Willebrand factor concentratehaemophilia Aimmune tolerance inductionpoor prognosis for immune tolerance inductionAdolescentAdultAntibodies, NeutralizingChildChild, PreschoolDrug CombinationsFactor VIIIFemaleHemophilia AHemorrhageHumansImmune ToleranceInfantMalePrognosisProspective StudiesRisk FactorsSafetyYoung Adultvon Willebrand Factorresearch article26202305open access10.1111/hae.127741365-2516https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/hae.12774