ITI Treatment is not First-Choice Treatment in Children with Hemophilia A and Low-Responding Inhibitors: Evidence from a PedNet Study.

Autor:	van den Berg HM; PedNet Foundation, Baarn, The Netherlands., Mancuso ME; Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Ospedale Maggiore Policlinico, Fondazione IRCCS Ca' Granda, Milan, Italy., Königs C; Department of Paediatrics and Adolescent Medicine, University Hospital Frankfurt, Frankfurt, Germany., D'Oiron R; Centre de Référence pour le Traitement des Maladies Hémorragiques, Hôpital Bicêtre, Paris, France., Platokouki H; Haemophilia Centre, Haemostasis Unit, 'Aghia Sophia' Children's Hospital, Athens, Greece., Mikkelsen TS; Division of Pediatric and Adolescent Medicine, Department of Clinical Medicine, Aarhus University Hospital, Aarhus, Denmark., Motwani J; Haematology Department, Birmingham Women's and Children's Hospital, Birmingham, United Kingdom., Nolan B; Our Lady's Children's Hospital Crumlin, Dublin, Ireland., Santagostino E; Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Ospedale Maggiore Policlinico, Fondazione IRCCS Ca' Granda, Milan, Italy.
Jazyk:	angličtina
Zdroj:	Thrombosis and haemostasis [Thromb Haemost] 2020 Aug; Vol. 120 (8), pp. 1166-1172. Date of Electronic Publication: 2020 Jun 22.
DOI:	10.1055/s-0040-1713097
Abstrakt:	Background:  Limited data exist on the clinical impact of low-responding inhibitors and the requirement for immune tolerance induction (ITI) treatment to establish tolerance, reduce bleeding, and improve outcome. The aim of this article is to describe the therapeutic management of children with severe hemophilia A and low-responding inhibitors and its effect on bleeding phenotype. Methods:  The REMAIN (Real-life Management of Inhibitors) study is a satellite study of the PedNet registry. It included unselected children with severe hemophilia A (factor VIII [FVIII] < 0.01 IU/mL) born between January 1, 1990 and December 31, 2009 who developed clinically relevant inhibitors and were followed-up for at least 3 years after the first positive inhibitor test. Results:  A total of 260 patients with inhibitors were identified and 68 of them (26%) had low-responding inhibitors (peak < 5 BU/mL). Five patients were lost to follow-up and 63 were included in this study. The median follow-up was 3.7 years (interquartile range: 3.0-7.5). ITI was started in 51/63 (81%) patients. The median time from ITI start to first negative inhibitor titer was similar with low-dose and high-dose ITI regimens (2.5 and 3.1 months, respectively). Ten of the 12 patients who did not receive ITI were treated with regular prophylaxis and reached a negative titer after a median of 6.5 months. Bleeding rate was low in all patients with no difference between treatment regimens. Conclusion:  In children with low-responding inhibitors negative titers were reached with regular FVIII treatment irrespective of the regimen (i.e., prophylaxis or ITI). Competing Interests: H.M.v.d.B. has received research grants from Bayer, Shire/Takeda, Novo Nordisk, CSL Behring, Pfizer, and Sobi; M.E.M. has acted as paid speaker/consultant for Bayer Healthcare, CSL Behring, Grifols, Roche, Kedrion, Pfizer, Novo Nordisk, Octapharma, Sobi, and Shire/Takeda; C.K. reports grants and personal fees from Bayer Vital GmbH, Biotest AG, CSL Behring, Grifols, Intersero, Pfizer, Sanofi, Sobi, Takeda, Jansen, Roche/Chugai, MSD, and Novo Nordisk; R.D.O. has received personal fees and nonfinancial support from Shire/Takeda, CSL Behring, LFB, Novo Nordisk, Octapharma, Roche, and Spark; H.P. has received honoraria from Bayer, Baxalta, CSL Behring, Novo Nordisk, Roche, Sobi, and Pfizer; T.S.M. has no conflicts to disclose; B.N. has received fees and research grants from Sanofi, Sobi, CSL Behring, and Bayer; E.S. has acted as paid speaker/consultant for Bayer Healthcare, CSL Behring, Grifols, Roche, Kedrion, Pfizer, Novo Nordisk, Octapharma, Sobi, Spark, Uniqure, and Shire/Takeda. (Georg Thieme Verlag KG Stuttgart · New York.)
Databáze:	MEDLINE
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