The international immune tolerance study (NCT00212472) showed that 40% of patients with severe haemophilia with inhibitors in the intent-to-treat population achieved immune tolerance, in a median time of approximately 22 months after rFVIIIFc treatment initiation. However, recent retrospective evidence suggested a higher success rate and rapid tolerization in patients who underwent ITI therapy for the first time2.
The current, global, prospective, verITI-8 study (NCT03093480) included 16 patients with severe haemophilia with inhibitors to administer first-time ITI therapy. The patients received rFVIIIFc therapy (200 IU/kg/day) for up to 48 weeks. If tolerization was achieved within this timeframe, the patients entered a 16-week tapering period and a 32-week follow-up period. The primary endpoint was time to tolerization.
Treatment success was defined as negative Bethesda titres plus normal recovery (incremental recovery ≥66%) on 2 consecutive visits and rFVIIIFc half-life ≥7 hours. Dr Lynn Malec (Versiti Blood Research Institute, WI, USA) presented the final results. Tolerization was achieved in 63% of the patients in a median time of 11.7 weeks. In addition, the median time to the first negative inhibitor titre was 7.4 weeks, and the median time to normal recovery was 6.8 weeks. No relapses were observed in the patients who achieved tolerization.
Bypassing agents aPCC and rFVIIa were consumed by 25% and 31.3% of the patients during the ITI period, respectively. The median annualised bleeding rates (ABRs) were 3.8 during the ITI period and 0.0 during the tapering and follow-up periods. In total, 9 patients experienced at least 1 serious treatment-emergent adverse event (AE).
However, none of these events were considered to be related to treatment. The serious treatment-emergent AEs included vascular device infections, contusions, and haemarthrosis. Importantly, no thrombotic events were reported.
1. Malec L, et al. Efficacy of rFVIIIFc for First-Time Immune Tolerance Induction (ITI) Therapy: Final Results From the Global, Prospective verITI-8 Study. LBA-5, ASH 2021 Scientific Sessions, 11-14 December.
2. Carcao M, et al. Haemophilia. 2021;27(1):19-25