OC 61.3 - More cost-effective of intermediate-dose immune tolerance induction regimen for severe hemophilia A children with high-titer inhibitors: the interim report of a randomized multicenter clinical trial

Tuesday, June 25, 2024

15:15 – 15:30 ICT

Room: Ballroom B1

Presenting Author(s)

Zhengping Li, Medical Doctor in progress

M.D. in progress
zhengp_li@163.com
Beijing, Beijing, China (People's Republic)

Co-Author(s)

MP

Man-Chiu Poon

Professor
University of Calgary
Calgary, Alberta, Canada
Runhui Wu, PhD, MD

Professor
Department of Hematology, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, 100045, China
Beijing, Beijing, China (People's Republic)

Background: Low-dose (LD) or intermediate-dose (MD) immune tolerance induction (ITI) are more cost-effective in severe hemophilia A (SHA) children with high-titer inhibitors (HTI) in developing countries with economic constraint. However, high-quality evidence for their use is lacking.

Aims: To conduct a multicenter randomized clinical trial (RCT) comparing the cost-effectiveness between LD-ITI and MD-ITI for SHA-HTI children.

Methods: SHA children ≤8year-age with historical/pre-ITI inhibitor titer 5-200 Bethesda Units/mL in 3 centers were randomized 1:1 to receive LD-ITI [recombinant (r)FVIII 50 IU/kg once-every-day] or MD-ITI (rFVIII 100 IU/kg/day) regimen from January 2022 to November 2023 (ChiCTR2200056603). Immunosuppressants (IS) was added for unsatisfactory inhibitor-decline. Success defined as negative inhibitor titer twice consecutively and FVIII recovery ≥66% of expected.

Results: Thirty-one patients (16 in MD-, 15 in LD-ITI) were enrolled and followed for ≥9 months (median 13.9, range 9.0-19.5 months).
The 2 groups have similar baseline clinical characteristics and similar success rate [93.8% (MD-ITI) vs. 73.3% (LD-ITI). Compared to LD-ITI, MD-ITI patients took shorter median time to success (3.8 months vs. 9.8 months), to partial success (2.7 months vs. 7.7 months), and had lower mean rate for all bleeding (0.38/month vs. 1.40/month) and joint bleeding (0.11/month vs. 0.83/month) (Figure 1).
Between the 2 groups, although MD-ITI group had higher rFVIII consumption (11558.3 vs. 7452.1 IU/kg), their total costs were similar (3383.32 vs. 3103.94 US$/kg) (Table 1).

Conclusion(s): For SHA-HTI children, success rate and cost for MD-ITI and LD-ITI regimens were similar. MD-ITI regimen would be a more cost-effective regimen than LD-ITI regimen for patients in developing countries, given its shorter time to success with better bleeding control.