New Inhibitors in the Ageing Population: A Retrospective, Observational, Cohort Study of New Inhibitors in Older People with Hemophilia

Abstract

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. Received: 27 April 2021 Accepted after revision: 09 September 2021 Publication Date: 10 September 2021 (online) © 2021. Thieme. All rights reserved. Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany