Introduction: A second peak of inhibitors has been reported in patients with severe haemophilia A (HA) aged >50 years in the UK.1 The reason for this suggested breakdown of tolerance in the ageing population is unclear, as is the potential impact of regular exposure to the deficient factor by prophylaxis at higher age. No data on haemophilia B (HB) has ever been reported. Aim: The ADVANCE Working Group investigated the incidence of late-onset inhibitors and the use of prophylaxis in patients with HA and HB aged ≥40 years. Methods: A retrospective, observational, cohort, survey-based study of all patients aged ≥40 years with HA or HB treated at an ADVANCE HTC. Results: Information on 3,095 people aged ≥40 years with HA or HB was collected. Of the 2,562 patients with severe HA, the majority (73% across all age groups) received prophylaxis. In patients with severe HA, the inhibitor incidence per 1,000 treatment years was 2.37 (age 40–49), 1.25 (age 50–59) and 1.45 (age 60+). Overall, the inhibitor incidence was greatest in those with moderate HA (5.77 (age 40–49), 6.59 (age 50–59) and 4.69 (age 60+) and the majority of inhibitor cases were preceded by a potential immune system challenge. No inhibitors in patients with haemophilia B were reported. Conclusion: Our data do not identify a second peak of inhibitor development in older patients with haemophilia. Prophylaxis may be beneficial in older patients with severe, and possibly moderate HA, to retain a tolerant state at higher age.

中文翻译：

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老龄化人群中的新抑制剂：一项针对老年血友病患者新抑制剂的回顾性、观察性、队列研究

引言：据报道，在英国 50 岁以上的严重血友病 A (HA) 患者中出现了第二个抑制物峰值。 1 导致老年人口耐受性下降的原因尚不清楚，常规治疗的潜在影响也是如此。在较高年龄通过预防暴露于缺乏因子。从未报道过关于血友病 B (HB) 的数据。目的：ADVANCE 工作组调查了年龄≥40 岁的 HA 和 HB 患者迟发性抑制剂的发生率和预防措施的使用。方法：一项回顾性、观察性、队列、基于调查的研究，对象为在 ADVANCE HTC 接受治疗的所有年龄≥40 岁的 HA 或 HB 患者。结果：收集了 3,095 名年龄≥40 岁的 HA 或 HB 患者的信息。在 2,562 名严重 HA 患者中，大多数（所有年龄组的 73%）接受了预防治疗。在重度 HA 患者中，每 1000 治疗年的抑制剂发生率为 2.37（40-49 岁）、1.25（50-59 岁）和 1.45（60 岁以上）。总体而言，中度 HA（5.77（40-49 岁）、6.59（50-59 岁）和 4.69（60 岁以上））的抑制剂发生率最高，并且大多数抑制剂病例之前都有潜在的免疫系统挑战。未报告血友病 B 患者中的抑制剂。结论：我们的数据未发现老年血友病患者出现第二个抑制物峰值。预防可能对患有严重和可能中度 HA 的老年患者有益，以保持耐受状态年龄较大。77（40-49 岁）、6.59（50-59 岁）和 4.69（60 岁以上）和大多数抑制剂病例之前都有潜在的免疫系统挑战。没有报告在血友病 B 患者中使用抑制剂。结论：我们的数据没有发现老年血友病患者出现第二个抑制物发展高峰。预防可能对患有重度和可能中度 HA 的老年患者有益，以在较高年龄时保持耐受状态。77（40-49 岁）、6.59（50-59 岁）和 4.69（60 岁以上）和大多数抑制剂病例之前都有潜在的免疫系统挑战。没有报告在血友病 B 患者中使用抑制剂。结论：我们的数据并未发现老年血友病患者出现第二个抑制物发展高峰。预防可能对患有重度和可能中度 HA 的老年患者有益，以在较高年龄时保持耐受状态。