OC 61.4 - Immune tolerance induction (ITI) strategies in haemophilia A patients with inhibitors – Interim analysis from the MOTIVATE study

Background: Several treatment options are available for haemophilia A patients with inhibitors. While emicizumab may prevent bleeding, immune tolerance induction (ITI) using factor VIII is the only method to eradicate inhibitors.

Aims: The investigator-initiated, international MOTIVATE study (NCT04023019) is investigating the management of haemophilia A patients with inhibitors. The objectives are to capture different treatment approaches and evaluate the efficacy and safety of ITI, emicizumab prophylaxis, and ITI with concurrent emicizumab prophylaxis.

Methods: Patients with haemophilia A and inhibitors will be observed for up to five years. The treatment approaches evaluated (Table 1) are ITI (Group 1), ITI with emicizumab prophylaxis (Group 2), and emicizumab prophylaxis (Group 3). Treatment decisions are at the discretion of the investigators. Primary endpoints are ITI success and annualised bleeding rates (ABRs). Target enrolment is 120 patients.

Results: An interim analysis was performed when 20 patients were documented for at least one year in Groups 1 and 2. The interim analysis population included 45 patients from 11 countries and 22 centres: 5 in Group 1 (4 high and 1 low responder), 19 in Group 2 (17 high and 2 low responders), and 21 in Group 3. The median (range) age at the start of observation was 1.8 (0.9–13.3), 3.5 (1–20), and 8.4 (1.1–64.9) years for Group 1, 2 and 3, respectively. During the study, 6 patients switched treatments (2 from Group 2 to 1, 2 from Group 2 to 3, and 2 from Group 3 to 2). 14 patients received rFVIII and 10 received pdFVIII/VWF. No serious adverse drug reactions or thrombotic events were reported.

Conclusion(s): The MOTIVATE study is collecting real-world data on the management of patients with haemophilia A and inhibitors. Results from the interim analysis will provide insights on the efficacy and safety of such approaches.