Perelman School of Medicine, The Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, Pennsylvania.
University of Michigan, Ann Arbor, Michigan.
Haemophilia. 2019 Jul;25(4):575-580. doi: 10.1111/hae.13737.
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.
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.
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.
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.
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.
甲型血友病蛋白替代疗法的主要并发症是抗 FVIII 抗体或抑制剂的产生，在 25%-30%的重度甲型血友病患者中会发生这种情况。替代疗法，如旁路制剂或免疫耐受诱导方案，存在额外的挑战，并不总是有效。
召集国家心肺血液研究所 (NHLBI) 科学现状 (SOS) 研讨会，为研究抑制剂制定国家研究蓝图，以解决 FVIII 免疫原性问题。
2017 年 10 月成立了一个执行指导委员会，以确定 SOS 研讨会的科学重点和科学工作组。2018 年 5 月成立了四个工作组，以解决抑制剂基础、转化和临床研究中的科学优先事项。
工作组 1负责确定临床试验的科学优先事项，包括将非静脉、非因子治疗方法（包括基因治疗）纳入有抑制剂的甲型血友病患者的标准治疗方案。工作组 2确定了 21 世纪数据科学和生物标本采集的科学优先事项，用于观察性抑制剂队列研究。工作组 3制定了获得对 FVIII 免疫原性和宿主反应及 FVIII 耐受的免疫学的可操作理解的科学优先事项。工作组 4设计了前瞻性妊娠/分娩队列，以研究 FVIII 免疫原性、抑制剂的产生和消除。
NHLBI SOS 研讨会提出了克服甲型血友病消除和预防抑制剂挑战的科学优先事项和实施策略的重点总结。
