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

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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

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Factor VIII
Hemophilia A
Surveys and Questionnaires
Confidence Intervals
Child Development
Neutralizing Antibodies

Keywords

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

ASJC Scopus subject areas

  • Hematology

Cite this

@article{e1b650bf4b134221ac74fa05857e530f,
title = "Timing and severity of inhibitor development in recombinant versus plasma-derived factor VIII concentrates: A SIPPET analysis",
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.",
keywords = "Antibodies, Factor VIII, Hemophilia A, Inhibitor, Plasma",
author = "F. Peyvandi and A. Cannav{\`o} and I. Garagiola and R. Palla and Mannucci, {P. M.} and Rosendaal, {F. R.}",
year = "2018",
doi = "10.1111/jth.13888",
language = "English",
volume = "16",
pages = "39--43",
journal = "Journal of Thrombosis and Haemostasis",
issn = "1538-7933",
publisher = "Wiley-Blackwell",
number = "1",

}

TY - JOUR

T1 - Timing and severity of inhibitor development in recombinant versus plasma-derived factor VIII concentrates

T2 - A SIPPET analysis

AU - Peyvandi, F.

AU - Cannavò, A.

AU - Garagiola, I.

AU - Palla, R.

AU - Mannucci, P. M.

AU - Rosendaal, F. R.

PY - 2018

Y1 - 2018

N2 - 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.

AB - 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.

KW - Antibodies

KW - Factor VIII

KW - Hemophilia A

KW - Inhibitor

KW - Plasma

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U2 - 10.1111/jth.13888

DO - 10.1111/jth.13888

M3 - Article

AN - SCOPUS:85034265899

VL - 16

SP - 39

EP - 43

JO - Journal of Thrombosis and Haemostasis

JF - Journal of Thrombosis and Haemostasis

SN - 1538-7933

IS - 1

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