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 language | English |
|---|---|
| Pages (from-to) | 39-43 |
| Number of pages | 5 |
| Journal | Journal of Thrombosis and Haemostasis |
| Volume | 16 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 01-01-2018 |
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All Science Journal Classification (ASJC) codes
- Hematology
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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 journal › Article
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.
UR - http://www.scopus.com/inward/record.url?scp=85034265899&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85034265899&partnerID=8YFLogxK
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
ER -