3 years ago

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

I. Garagiola, F. R Rosendaal, F. Peyvandi, P. M Mannucci, A. Cannavò, , R. Palla
Background The development of neutralizing antibodies (inhibitors) against factor VIII (FVIII) is the most severe complication in the early phases of treatment of severe haemophilia A. Recently a randomized trial, the Survey of Inhibitors in Plasma-Product Exposed Toddlers (SIPPET) demonstrated a two-fold higher risk of inhibitors 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 ED: hazard ratio 3.14 (CI95% 1.01-9.74) for all inhibitors and 4.19 (CI95% 1.18-14.8) for high-titre inhibitors. For patients treated with pdFVIII, the peak of inhibitor development occurred later (6-10 EDs) and lasted shorter. 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. This article is protected by copyright. All rights reserved.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1111/jth.13888

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