Abstract Number: PB1058
Meeting: ISTH 2020 Congress
Theme: Hemophilia and Rare Bleeding Disorders » Hemophilia - Clinical
Background: The eradication of inhibitors in patients with severe hemophilia A during immune tolerance induction (ITI) is a great challenge, especially if high dose ITI was not successful. Treatment success is evaluated by inhibitor titers, FVIII recovery, and half-life.
Aims: The change of IgG subtypes during ITI has not been evaluated in detail.
Methods: We report the course of a boy with severe hemophilia A, who was monitored for more than 4 years for coagulation, pharmacokinetic and immunological parameters (FVIII specific antibodies, isotypes, IgG subclasses, inhibitor titers) during ITI.
Results: The 5 years old boy developed high titer inhibitor (150 BU), increasing to 881 BU during ITI. After 10 months of ITI the inhibitor was 0.6 BU, increased after CVL infection to 7 BE and decreased very slowly without reaching < 2 BU. A change to rFVIIIFc resulted in only temporary improvement. After 3 years of ITI, treatment was switched to emicizumab and the ITI Atlanta protocol (rFVIIIFc 100IE/kg 3x/week). After initial increase to 12.4 BU, inhibitor dropped down to < 0.6BU.
Initially, the FVIII specific antibodies belonged mainly to IgG1 together with IgG3 and IgG4 at high levels. IgG1, 3 and 4 increased after infection and vaccination. They did not decrease further but reached a plateau during ITI. After switch to emicizumab and a low dose ITI protocol all 3 subclasses IgG1, IgG3 and 4 increased again with a predominance of IgG4. The IgGs bound to the HC, A2, LC C1 and C2 domains of FVIII. Over time IgG1 and 3 decreased, while IgG4 reached a plateau. After 1 year only IgG4 was highly positive, IgG1 was barely detectable. They bound only to LC and C1.
Conclusions: Low-dose ITI can be effective in the presence of emicizumab even after failing first line high dose ITI. Antibody titers mirrored the clinical courses.
To cite this abstract in AMA style:
Wieland I, Lambeck K-, Stichel D, Orlowski A, Königs C. Case report: Inhibitor Improvement with Low Dose Immune Tolerance Induction (ITI) with rFVIIIFc and Emicizumab after Failed First Line Therapy with High Dose ITI [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/case-report-inhibitor-improvement-with-low-dose-immune-tolerance-induction-iti-with-rfviiifc-and-emicizumab-after-failed-first-line-therapy-with-high-dose-iti/. Accessed July 28, 2021.« Back to ISTH 2020 Congress
ISTH Congress Abstracts - https://abstracts.isth.org/abstract/case-report-inhibitor-improvement-with-low-dose-immune-tolerance-induction-iti-with-rfviiifc-and-emicizumab-after-failed-first-line-therapy-with-high-dose-iti/