The use of a national registry and patient reported treatment records to evaluate outcomes in persons with haemophilia A managed with emicizumab in UK clinical practice

Abstract

Emicizumab is a novel factor VIII (FVIII) mimetic used for prophylaxis in haemophilia A. Real world evidence is required to confirm the efficacy in clinical practice, provide long-term safety data, and contribute to the understanding of issues not addressed in phase III trials. UK national registry and patient reported outcome (PRO) data are used to assess the clinical impact of emicizumab. Uptake, efficacy and safety of emicizumab including uncommon serious adverse events, that may not be well represented in clinical trials, are analysed. Two distinct but related populations are considered; persons with haemophilia A with inhibitors (PwHA-I) and persons with severe haemophilia A (PwSHA) without active inhibitors. For the latter population, in whom FVIII prophylaxis is generally effective, the effects of emicizumab on quality of life are also examined. During the study, 138 (52.3%) of the UK inhibitor and 618 (40.3%) of the non-inhibitor populations switched to emicizumab. Higher baseline bleeding rates were observed in emicizumab switchers, in both cohorts, when compared to people continuing conventional treatment. PwHA-I were generally older, had worse joint health and higher peak inhibitor titres than non-switchers. In PwSHA, without active inhibitors an inhibitor history was associated with lower rates of emicizumab uptake. Clinically and statistically significant improvements in bleeding outcomes were demonstrated in both populations on within-person comparison of emicizumab with prior therapy. An 89% reduction in annualised bleed rate (ABR) was observed in 89 PwHA-I using emicizumab. The median (IQR) post switch ABR was 0 (0,0) and zero-treated bleed (ZTB) rates increased from 45 to 88% (p

Date of Award	7 Mar 2024
Original language	English
Awarding Institution	The University of Manchester
Supervisor	John Burthem (Main Supervisor) & Charles Hay (Co Supervisor)