Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, IRCCS Ca' Granda Ospedale Maggiore Policlinico Foundation, Milan, Italy.
Blood. 2017 Oct 12;130(15):1757-1759. doi: 10.1182/blood-2017-06-791756. Epub 2017 Aug 2.
A recent randomized trial, the Survey of Inhibitors in Plasma-Product Exposed Toddlers (SIPPET), showed a higher risk of inhibitor development with recombinant factor VIII (rFVIII) than plasma-derived concentrates (pdFVIII). We investigated whether risk stratification by F8 mutation identifies patients who do not suffer this deleterious effect of rFVIII. Among 235 randomized patients with severe hemophilia A previously untreated with FVIII concentrate, 197 with null mutations were classified as high risk and 38 with non-null mutations were classified as low risk. With pdFVIII, no inhibitors occurred in those with low genetic risk, whereas high-risk patients had a cumulative incidence of 31%. The risk among low- and high-risk patients did not differ much when they were treated with rFVIII (43% and 47%, respectively). This implies that patients with low genetic risk suffer disproportionate harm when treated with rFVIII (risk increment 43%), as also shown by the number needed to harm with rFVIII, which was 6.3 for genetically high-risk patients and only 2.3 for low-risk patients. Risk stratification by F8 mutation does not identify patients who can be safely treated with rFVIII, as relates to immunogenicity. This trial was registered at the European Clinical Trials Database (EudraCT) as #2009-011186-88 and at www.clinicaltrials.gov as #NCT01064284.
最近的一项随机试验，即血浆制品暴露幼儿抑制剂调查（SIPPET）表明，与血浆衍生浓缩物（pdFVIII）相比，重组因子 VIII（rFVIII）导致抑制剂发展的风险更高。我们研究了 F8 突变的风险分层是否可以识别不会遭受 rFVIII 这种有害影响的患者。在 235 名以前未接受 FVIII 浓缩物治疗的严重 A 型血友病随机患者中，197 名具有无义突变的患者被归类为高危，38 名具有非无义突变的患者被归类为低危。对于 pdFVIII，低遗传风险的患者没有发生抑制剂，而高风险患者的累积发生率为 31%。当用 rFVIII 治疗时，低风险和高风险患者之间的风险差异不大（分别为 43%和 47%）。这意味着，用 rFVIII 治疗时，低遗传风险的患者遭受不成比例的伤害（风险增加 43%），这也可以通过用 rFVIII 治疗所需的人数来证明，对于遗传高风险患者，需要 6.3 人，而对于低风险患者，仅需要 2.3 人。F8 突变的风险分层不能识别可以安全用 rFVIII 治疗的患者，因为这与免疫原性有关。该试验在欧洲临床试验数据库（EudraCT）中注册为 #2009-011186-88，在美国国立卫生研究院临床试验数据库（www.clinicaltrials.gov）中注册为 #NCT01064284。
