Hay C R M, Palmer B P, Chalmers E A, Hart D P, Liesner R, Rangarajan S, Talks K, Williams M, Collins P W
Manchester University Department of Haematology, Manchester Royal Infirmary, Manchester, UK.
The UK National Haemophilia Database, Manchester, UK.
Haemophilia. 2015 Mar;21(2):219-226. doi: 10.1111/hae.12563. Epub 2014 Nov 7.
Although it has been suggested that switching of factor VIII (FVIII) products may increase inhibitor formation this is disputed. Half of UK patients changed rFVIII brands because of national contracting in 2010, presenting an opportunity to compare inhibitor incidence of switchers with non-switchers. Centres were requested to test all the patients for inhibitors prior to the switching date and 6-monthly thereafter. Positive and negative inhibitor test data were also collected to analyse for testing bias. A total of 1198 patients with severe haemophilia A and treated with Advate, Kogenate/Helixate or Refacto AF preswitch were included in the analysis, of whom 516 switched to Refacto-AF and 682 did not switch products. Five new inhibitors were reported amongst previously treated patients (>50 exposure days) with a median titre at the time of detection of 1.25 BU mL(-1) (IQR 0.7-23.05). One inhibitor occurred in a non-switcher using Kogenate, an incidence of 1.5 per 1000 treatment-years (95% CI 0.2-10.5). Four inhibitors arose in patients who had switched from Kogenate (two) or Advate (two) to ReFacto-AF, an incidence of 7.8 per 1000 treatment-years (95% CI 2.9-20.8). These incidence rates did not differ significantly from one another (incidence rate ratio 5.3 (95% CI 0.5-260.3) or from the historical rate of 6.05 inhibitors/1000 treatment-years (95% CI 5.18-7.06). Only one inhibitor (non-switcher) persisted. Non-switchers were significantly older (P = 0.03), and used significantly less FVIII per year (P = 0.005) prior to switching. Following switching, factor usage increased similarly (P = 0.53) in both groups. Switching from FLRFVIII to Refacto-AF (BDDRFVIII) was not associated with an increased inhibitor development.
尽管有人认为更换凝血因子VIII（FVIII）产品可能会增加抑制剂的形成，但这一观点存在争议。2010年，英国有一半的患者因国家采购合同而更换了重组FVIII品牌，这为比较更换者和未更换者的抑制剂发生率提供了一个机会。各中心被要求在更换日期之前对所有患者进行抑制剂检测，此后每6个月检测一次。还收集了阳性和阴性抑制剂检测数据，以分析检测偏差。共有1198例重度A型血友病患者在更换产品前接受了Advate、Kogenate/Helixate或Refacto AF治疗，其中516例更换为Refacto-AF，682例未更换产品。在先前接受治疗的患者（暴露天数>50天）中报告了5例新的抑制剂，检测时的中位滴度为1.25 BU mL（-1）（四分位间距0.7-23.05）。1例抑制剂出现在使用Kogenate的未更换者中，发生率为每1000治疗年1.5例（95%可信区间0.2-10.5）。4例抑制剂出现在从Kogenate（2例）或Advate（2例）更换为ReFacto-AF的患者中，发生率为每1000治疗年7.8例（95%可信区间2.9-20.8）。这些发生率之间没有显著差异（发生率比值5.3（95%可信区间0.5-260.3）），也与历史发生率6.05例抑制剂/1000治疗年（95%可信区间5.18-7.06）没有显著差异。只有1例抑制剂（未更换者）持续存在。未更换者年龄显著较大（P = 0.03），在更换前每年使用的FVIII显著较少（P = 0.005）。更换后，两组的因子使用量增加情况相似（P = 0.53）。从FLRFVIII更换为Refacto-AF（BDDRFVIII）与抑制剂形成增加无关。
