Timing and severity of inhibitor development in recombinant versus plasma-derived factor VIII concentrates: A SIPPET analysis

Research output: Contribution to journalArticle

Abstract

Essentials: Recombinant factor VIII (rFVIII) was contrasted with plasma-derived FVIII (pdFVIII). In previously untreated patients with hemophilia A, rFVIII led to more inhibitors than pdFVIII. Inhibitors with rFVIII developed earlier, and the peak rate was higher than with pdFVIII. Inhibitors with rFVIII were more severe (higher titre) than with pdFVIII. Summary: Background: The development of neutralizing antibodies (inhibitors) against factor VIII (FVIII) is the most severe complication in the early phases of treatment of severe hemophilia A. Recently, a randomized trial, the Survey of Inhibitors in Plasma-Product Exposed Toddlers (SIPPET) demonstrated a 2-fold higher risk of inhibitor development in children treated with recombinant FVIII (rFVIII) products than with plasma-derived FVIII (pdFVIII) during the first 50 exposure days (EDs). Objective/Methods: In this post-hoc SIPPET analysis we evaluated the rate of inhibitor incidence over time by every 5 EDs (from 0 to 50 EDs) in patients treated with different classes of FVIII product, made possible by a frequent testing regime. Results: The highest rate of inhibitor development occurred in the first 10 EDs, with a large contrast between rFVIII and pdFVIII during the first 5 EDs: hazard ratio 3.14 (95% confidence interval [CI], 1.01-9.74) for all inhibitors and 4.19 (95% CI, 1.18-14.8) for high-titer inhibitors. For patients treated with pdFVIII, the peak of inhibitor development occurred later (6-10 EDs) and lasted for a shorter time. Conclusion: These results emphasize the high immunologic vulnerability of patients during the earliest exposure to FVIII concentrates, with the strongest response to recombinant FVIII products.

Original languageEnglish
Pages (from-to)39-43
JournalJournal of Thrombosis and Haemostasis
Volume16
Issue number1
DOIs
Publication statusPublished - 2018

    Fingerprint

Keywords

  • Antibodies
  • Factor VIII
  • Hemophilia A
  • Inhibitor
  • Plasma

ASJC Scopus subject areas

  • Hematology

Cite this