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

the SIPPET Study Group

Research output: Contribution to journalArticle

7 Citations (Scopus)

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
Number of pages5
JournalJournal of Thrombosis and Haemostasis
Volume16
Issue number1
DOIs
Publication statusPublished - 01-01-2018

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

All Science Journal Classification (ASJC) codes

  • Hematology

Cite this

@article{dc31968ef0604656ba41bd39bae819ff,
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.",
author = "{the SIPPET Study Group} and F. Peyvandi and A. Cannav{\`o} and I. Garagiola and R. Palla and Mannucci, {P. M.} and Rosendaal, {F. R.} and A. El-Beshlawy and M. Elalfy and V. Ramanan and P. Eshghi and S. Hanagavadi and R. Varadarajan and M. Karimi and Manglani, {M. V.} and C. Ross and G. Young and T. Seth and S. Apte and Nayak, {D. M.} and E. Santagostino and {Elisa Mancuso}, M. and {Sandoval Gonzalez}, {A. C.} and Mahlangu, {J. N.} and {Bonanad Boix}, S. and M. Cerqueira and Ewing, {N. P.} and C. Male and T. Owaidah and {Soto Arellano}, V. and Kobrinsky, {N. L.} and S. Majumdar and {Perez Garrido}, R. and A. Sachdeva and M. Simpson and M. Thomas and E. Zanon and B. Antmen and K. Kavakl and Manco-Johnson, {M. J.} and M. Martinez and E. Marzouka and Mazzucconi, {M. G.} and D. Neme and {Palomo Bravo}, A. and {Paredes Aguilera}, R. and A. Prezotti and K. Schmitt and Wicklund, {B. M.} and B. Zulfikar",
year = "2018",
month = "1",
day = "1",
doi = "10.1111/jth.13888",
language = "English",
volume = "16",
pages = "39--43",
journal = "Journal of Thrombosis and Haemostasis",
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publisher = "Wiley-Blackwell",
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Timing and severity of inhibitor development in recombinant versus plasma-derived factor VIII concentrates : a SIPPET analysis. / the SIPPET Study Group.

In: Journal of Thrombosis and Haemostasis, Vol. 16, No. 1, 01.01.2018, p. 39-43.

Research output: Contribution to journalArticle

TY - JOUR

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

T2 - a SIPPET analysis

AU - the SIPPET Study Group

AU - Peyvandi, F.

AU - Cannavò, A.

AU - Garagiola, I.

AU - Palla, R.

AU - Mannucci, P. M.

AU - Rosendaal, F. R.

AU - El-Beshlawy, A.

AU - Elalfy, M.

AU - Ramanan, V.

AU - Eshghi, P.

AU - Hanagavadi, S.

AU - Varadarajan, R.

AU - Karimi, M.

AU - Manglani, M. V.

AU - Ross, C.

AU - Young, G.

AU - Seth, T.

AU - Apte, S.

AU - Nayak, D. M.

AU - Santagostino, E.

AU - Elisa Mancuso, M.

AU - Sandoval Gonzalez, A. C.

AU - Mahlangu, J. N.

AU - Bonanad Boix, S.

AU - Cerqueira, M.

AU - Ewing, N. P.

AU - Male, C.

AU - Owaidah, T.

AU - Soto Arellano, V.

AU - Kobrinsky, N. L.

AU - Majumdar, S.

AU - Perez Garrido, R.

AU - Sachdeva, A.

AU - Simpson, M.

AU - Thomas, M.

AU - Zanon, E.

AU - Antmen, B.

AU - Kavakl, K.

AU - Manco-Johnson, M. J.

AU - Martinez, M.

AU - Marzouka, E.

AU - Mazzucconi, M. G.

AU - Neme, D.

AU - Palomo Bravo, A.

AU - Paredes Aguilera, R.

AU - Prezotti, A.

AU - Schmitt, K.

AU - Wicklund, B. M.

AU - Zulfikar, B.

PY - 2018/1/1

Y1 - 2018/1/1

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.

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DO - 10.1111/jth.13888

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