Final Results of the Prospective ADVATE® Immune Tolerance Induction Registry (PAIR) Study with Plasma- and Albumin-Free Recombinant Factor VIII

Final Results of the Prospective ADVATE® Immune Tolerance Induction Registry (PAIR) Study with Plasma- and Albumin-Free Recombinant Factor VIII

Amy D Shapiro,1 Alejandro Fernandez,2 Jerome Teitel,3 Jaco Botha,2 Kate Khair4 1Indiana Hemophilia & Thrombosis Center, Indianapolis, IN, USA; 2Takeda Pharmaceutical International AG, Zürich, Switzerland; 3St. Michael’s Hospital, University of Toronto, Toronto, ON, Canada; 4Centre for Outcomes a...

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Autores principales: Shapiro AD, Fernandez A, Teitel J, Botha J, Khair K
Formato: article
Lenguaje:EN
Publicado: Dove Medical Press 2021
Materias:
hemophilia a
immune tolerance
post-marketing product surveillance
therapeutics
adverse effects
Diseases of the blood and blood-forming organs
RC633-647.5
Acceso en línea:https://doaj.org/article/e8f7b0a0de8f401b952367e5ac65e494
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spelling oai:doaj.org-article:e8f7b0a0de8f401b952367e5ac65e4942021-11-21T19:08:51ZFinal Results of the Prospective ADVATE® Immune Tolerance Induction Registry (PAIR) Study with Plasma- and Albumin-Free Recombinant Factor VIII1179-2736https://doaj.org/article/e8f7b0a0de8f401b952367e5ac65e4942021-11-01T00:00:00Zhttps://www.dovepress.com/final-results-of-the-prospective-advate-immune-tolerance-induction-reg-peer-reviewed-fulltext-article-JBMhttps://doaj.org/toc/1179-2736Amy D Shapiro,1 Alejandro Fernandez,2 Jerome Teitel,3 Jaco Botha,2 Kate Khair4 1Indiana Hemophilia & Thrombosis Center, Indianapolis, IN, USA; 2Takeda Pharmaceutical International AG, Zürich, Switzerland; 3St. Michael’s Hospital, University of Toronto, Toronto, ON, Canada; 4Centre for Outcomes and Experience Research in Children’s Health Illness and Disability (ORCHID), Great Ormond Street Hospital, London, UKCorrespondence: Jaco BothaTakeda Pharmaceutical International AG, Thurgauerstrasse 130, Glattpark-Opfikon, Zürich, 8152, SwitzerlandTel +41 79 961 8561Email jaco.botha@takeda.comIntroduction: Neutralizing antibodies to coagulation factor VIII (FVIII) remain a major complication associated with FVIII replacement therapy.Aim: To assess safety and efficacy of immune tolerance induction (ITI) therapy with ADVATE® (antihemophilic factor [recombinant] [rAHF]) in patients who participated in the Prospective ADVATE Immune Tolerance Induction Registry (PAIR) study.Methods: The PAIR study was an international, multicenter, open-label, prospective, observational study in patients with hemophilia A and inhibitors, prescribed rAHF ITI therapy in clinical practice. The primary endpoint was adverse event (AE) reporting; the secondary endpoints included incidence of central venous access device-related complications and success rates of ITI therapy. Maintenance of immune tolerance was monitored for 12 months post-ITI therapy.Results: Of 44 patients, 36 completed ITI therapy, including 31 completing the 12-month follow-up. Most patients received rAHF 90– 130 IU/kg/day (59.1%) and a mean of 6.0 doses/week; the median duration of rAHF ITI therapy during the PAIR study was 600 days. Overall, 284 AEs were reported; 56 AEs were serious, of which none were considered rAHF-related. Of 228 nonserious AEs, 14 (in six patients) were deemed rAHF-related: increase of FVIII inhibitors titer due to anamnestic response, nausea, catheter site pain, pyrexia, urticaria, upper respiratory tract infection, arthralgia, and hemarthrosis. None were severe or led to ITI discontinuation. Eighteen patients experienced ≥ 1 central venous access device-related complication, and 21 of 36 completers achieved a negative inhibitor titer. The Kaplan–Meier estimate of success for achievement of first negative titer at 18 months of ITI therapy was 68.3% (95% confidence interval 51.8– 83.6%) among completers. Of patients with partial or complete success post-ITI, 87% (20/23) maintained immune tolerance at 12-month follow-up.Conclusion: Data suggest that rAHF ITI therapy in the PAIR study was effective, with no unexpected safety signals reported.Keywords: hemophilia A, immune tolerance, post-marketing product surveillance, therapeutics, adverse effectsShapiro ADFernandez ATeitel JBotha JKhair KDove Medical Pressarticlehemophilia aimmune tolerancepost-marketing product surveillancetherapeuticsadverse effectsDiseases of the blood and blood-forming organsRC633-647.5ENJournal of Blood Medicine, Vol Volume 12, Pp 991-1001 (2021)
institution DOAJ
collection DOAJ
language EN
topic hemophilia a
immune tolerance
post-marketing product surveillance
therapeutics
adverse effects
Diseases of the blood and blood-forming organs
RC633-647.5
spellingShingle hemophilia a
immune tolerance
post-marketing product surveillance
therapeutics
adverse effects
Diseases of the blood and blood-forming organs
RC633-647.5
Shapiro AD
Fernandez A
Teitel J
Botha J
Khair K
Final Results of the Prospective ADVATE® Immune Tolerance Induction Registry (PAIR) Study with Plasma- and Albumin-Free Recombinant Factor VIII
description Amy D Shapiro,1 Alejandro Fernandez,2 Jerome Teitel,3 Jaco Botha,2 Kate Khair4 1Indiana Hemophilia & Thrombosis Center, Indianapolis, IN, USA; 2Takeda Pharmaceutical International AG, Zürich, Switzerland; 3St. Michael’s Hospital, University of Toronto, Toronto, ON, Canada; 4Centre for Outcomes and Experience Research in Children’s Health Illness and Disability (ORCHID), Great Ormond Street Hospital, London, UKCorrespondence: Jaco BothaTakeda Pharmaceutical International AG, Thurgauerstrasse 130, Glattpark-Opfikon, Zürich, 8152, SwitzerlandTel +41 79 961 8561Email jaco.botha@takeda.comIntroduction: Neutralizing antibodies to coagulation factor VIII (FVIII) remain a major complication associated with FVIII replacement therapy.Aim: To assess safety and efficacy of immune tolerance induction (ITI) therapy with ADVATE® (antihemophilic factor [recombinant] [rAHF]) in patients who participated in the Prospective ADVATE Immune Tolerance Induction Registry (PAIR) study.Methods: The PAIR study was an international, multicenter, open-label, prospective, observational study in patients with hemophilia A and inhibitors, prescribed rAHF ITI therapy in clinical practice. The primary endpoint was adverse event (AE) reporting; the secondary endpoints included incidence of central venous access device-related complications and success rates of ITI therapy. Maintenance of immune tolerance was monitored for 12 months post-ITI therapy.Results: Of 44 patients, 36 completed ITI therapy, including 31 completing the 12-month follow-up. Most patients received rAHF 90– 130 IU/kg/day (59.1%) and a mean of 6.0 doses/week; the median duration of rAHF ITI therapy during the PAIR study was 600 days. Overall, 284 AEs were reported; 56 AEs were serious, of which none were considered rAHF-related. Of 228 nonserious AEs, 14 (in six patients) were deemed rAHF-related: increase of FVIII inhibitors titer due to anamnestic response, nausea, catheter site pain, pyrexia, urticaria, upper respiratory tract infection, arthralgia, and hemarthrosis. None were severe or led to ITI discontinuation. Eighteen patients experienced ≥ 1 central venous access device-related complication, and 21 of 36 completers achieved a negative inhibitor titer. The Kaplan–Meier estimate of success for achievement of first negative titer at 18 months of ITI therapy was 68.3% (95% confidence interval 51.8– 83.6%) among completers. Of patients with partial or complete success post-ITI, 87% (20/23) maintained immune tolerance at 12-month follow-up.Conclusion: Data suggest that rAHF ITI therapy in the PAIR study was effective, with no unexpected safety signals reported.Keywords: hemophilia A, immune tolerance, post-marketing product surveillance, therapeutics, adverse effects
format article
author Shapiro AD
Fernandez A
Teitel J
Botha J
Khair K
author_facet Shapiro AD
Fernandez A
Teitel J
Botha J
Khair K
author_sort Shapiro AD
title Final Results of the Prospective ADVATE® Immune Tolerance Induction Registry (PAIR) Study with Plasma- and Albumin-Free Recombinant Factor VIII
title_short Final Results of the Prospective ADVATE® Immune Tolerance Induction Registry (PAIR) Study with Plasma- and Albumin-Free Recombinant Factor VIII
title_full Final Results of the Prospective ADVATE® Immune Tolerance Induction Registry (PAIR) Study with Plasma- and Albumin-Free Recombinant Factor VIII
title_fullStr Final Results of the Prospective ADVATE® Immune Tolerance Induction Registry (PAIR) Study with Plasma- and Albumin-Free Recombinant Factor VIII
title_full_unstemmed Final Results of the Prospective ADVATE® Immune Tolerance Induction Registry (PAIR) Study with Plasma- and Albumin-Free Recombinant Factor VIII
title_sort final results of the prospective advate® immune tolerance induction registry (pair) study with plasma- and albumin-free recombinant factor viii
publisher Dove Medical Press
publishDate 2021
url https://doaj.org/article/e8f7b0a0de8f401b952367e5ac65e494
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