Denise E Sabatino1, Steven W Pipe2, Diane J Nugent3, J Michael Soucie4, W Craig Hooper4, W Keith Hoots5, Donna M DiMichele5. 1. Perelman School of Medicine, The Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, Pennsylvania. 2. University of Michigan, Ann Arbor, Michigan. 3. Children's Hospital of Orange County, University of California at Irvine, Irvine, California. 4. Division of Blood Disorders, Centers for Disease Control and Prevention, Atlanta, Georgia. 5. Division of Blood Diseases and Resources, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland.
Abstract
INTRODUCTION: The major complication of protein replacement therapy for haemophilia A is the development of anti-FVIII antibodies or inhibitors that occur in 25%-30% of persons with severe haemophilia A. Alternative therapeutics such as bypassing agents or immune tolerance induction protocols have additional challenges and are not always effective. AIM: Assemble a National Heart, Lung and Blood Institute (NHLBI) State of the Science (SOS) Workshop to generate a national blueprint for research on inhibitors to solve the problem of FVIII immunogenicity. METHODS: An Executive Steering Committee was formed in October 2017 to establish the scientific focus and Scientific Working Groups for the SOS Workshop in May 2018. Four working groups were assembled to address scientific priorities in basic, translational and clinical research on inhibitors. RESULTS: Working Group 1 was charged with determining the scientific priorities for clinical trials to include the integration of non-intravenous, non-factor therapeutics including gene therapy into the standard of care for people with haemophilia A with inhibitors. Working Group 2 established the scientific priorities for 21st-century data science and biospecimen collection for observational inhibitor cohort studies. The scientific priorities for acquiring an actionable understanding of FVIII immunogenicity and the immunology of the host response and FVIII tolerance were developed by Working Group 3. Working Group 4 designed prospective pregnancy/birth cohorts to study FVIII immunogenicity, inhibitor development and eradication. CONCLUSION: The NHLBI SOS Workshop generated a focused summary of scientific priorities and implementation strategies to overcome the challenges of eradicating and preventing inhibitors in haemophilia A.
INTRODUCTION: The major complication of protein replacement therapy for haemophilia A is the development of anti-FVIII antibodies or inhibitors that occur in 25%-30% of persons with severe haemophilia A. Alternative therapeutics such as bypassing agents or immune tolerance induction protocols have additional challenges and are not always effective. AIM: Assemble a National Heart, Lung and Blood Institute (NHLBI) State of the Science (SOS) Workshop to generate a national blueprint for research on inhibitors to solve the problem of FVIII immunogenicity. METHODS: An Executive Steering Committee was formed in October 2017 to establish the scientific focus and Scientific Working Groups for the SOS Workshop in May 2018. Four working groups were assembled to address scientific priorities in basic, translational and clinical research on inhibitors. RESULTS: Working Group 1 was charged with determining the scientific priorities for clinical trials to include the integration of non-intravenous, non-factor therapeutics including gene therapy into the standard of care for people with haemophilia A with inhibitors. Working Group 2 established the scientific priorities for 21st-century data science and biospecimen collection for observational inhibitor cohort studies. The scientific priorities for acquiring an actionable understanding of FVIII immunogenicity and the immunology of the host response and FVIII tolerance were developed by Working Group 3. Working Group 4 designed prospective pregnancy/birth cohorts to study FVIII immunogenicity, inhibitor development and eradication. CONCLUSION: The NHLBI SOS Workshop generated a focused summary of scientific priorities and implementation strategies to overcome the challenges of eradicating and preventing inhibitors in haemophilia A.
Authors: Steven W Pipe; Denise E Sabatino; Diane J Nugent; W Craig Hooper; J Michael Soucie; W Keith Hoots; Donna M DiMichele Journal: Haemophilia Date: 2019-07 Impact factor: 4.287
Authors: H Eichler; P Angchaisuksiri; K Kavakli; P Knoebl; J Windyga; V Jiménez-Yuste; A Hyseni; U Friedrich; P Chowdary Journal: J Thromb Haemost Date: 2018-09-30 Impact factor: 5.824
Authors: Johannes Oldenburg; Johnny N Mahlangu; Willem Bujan; Peter Trask; Michael U Callaghan; Guy Young; Elina Asikanius; Flora Peyvandi; Elena Santagostino; Rebecca Kruse-Jarres; Claude Negrier; Craig Kessler; Jin Xu; Jerzy Windyga; Midori Shima; Sylvia von Mackensen Journal: Haemophilia Date: 2018-11-14 Impact factor: 4.287
Authors: Leonard A Valentino; Michelle L Witkop; Maria E Santaella; Donna DiMichele; Michael Recht Journal: Haemophilia Date: 2022-06-14 Impact factor: 4.263