Abstract Number: PB0511
Meeting: ISTH 2021 Congress
Theme: Hemophilia and Rare Bleeding Disorders » Hemophilia - Clinical
Background: Real-world reports of outcomes of emicizumab prophylaxis in severe haemophilia A (SHA) without inhibitors are limited.
Aims: To evaluate the efficacy and safety of emicizumab across the UK
Methods: This prospective, observational study used registry and Haemtrack (HT) patient reported outcome data from patients prescribed emicizumab between 01/08/2019-30/09/2020. Short-term efficacy (ABR, AJBR and bleed-free proportion) were determined and compared with prior FVIII prophylaxis (within-person analysis) in patients with ≥ 6 months HT data before and after switching. Adverse events (AE) were adjudicated by the Co-Morbidities Working Party.
Results: Emicizumab was prescribed to 378 subjects, median (IQR) age 36.0 (31.0; 45.5), including 83 <18 years – 15 were previously untreated and 18 minimally treated patients. Within-person comparison in 179 with ≥ 6 months pre/post switching HT data (including 40 using rFVIIIFc prophylaxis), demonstrated significant reduction in bleeding rates with emicizumab (table). The overall bleed-free proportion increased from 37% to 75% in the 36 weeks before and after switching (P<0.001). A sub-analysis of the 44/179 who reported bleeding after switching showed a higher median (IQR) pre-switch ABR of 5.21 (2.20; 16.0) reducing to 1.90 (1.52; 3.67) post; a change of -3.22 (-10.0; -0.36), (p< 0.001). AEs, reported in 9/378 (2.4%), occurred predominantly during loading and included: grade 1-2 cutaneous reactions in three, severe headaches in three (resulting in drug cessation in one) and poor efficacy, unrelated to anti-drug antibodies, in one person who reverted to rFVIIIFc prophylaxis. Recurrence of a FVIII inhibitor (Bethesda negative for ~ 4 years) was reported after 6 months emicizumab therapy without factor VIII exposure. One death, unrelated to emicizumab, was reported. No thrombotic or microangiopathic events occurred.
Conclusions:
| Follow-up (weeks) | Med. (IQR) age (years) |
Med. (IQR) ABR | Med. (IQR) AJBR | Bleed-free n (%)† |
Med. (IQR) change in ABR | |
|---|---|---|---|---|---|---|
| All products pre-switch n=179* | 103 (94;109) | 30 (14.0; 46.0) | 2.46 (0.5; 7.1) | 1.37 (0.0; 4.7) | 67 (37) | -2.15 (-6.36; 0.08) P <0.00 |
| Emicizumab post-switch | 36.0 (30.0; 44.0) | 0.0 (0.0;0.0) | 0.0 (0.0;0.0) | 135 (75) P <0.001 |
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| rFVIII pre-switch n=134* |
104 (94; 109) | 31 (13; 46) | 2.6 (0.5; 8.1) | 1.6 (0.0; 4.8) | 49 (37) | -2.48 (-6.69; -0.04) P <0.001 |
| Emicizumab post-switch | 35 (30; 42) | 0.0 (0.0;0.0) | 0.0 (0.0;0.0) | 103 (77) P <0.001 |
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| rFVIIIFc pre-switch n=40* |
100 (94.8; 107) | 30.5 (18.5; 47.8) |
2.19 (0.6; 5.4) | 1.06 (0.0: 3.4) | 16 (40) | -1.38 (-3.83; 0.00) P <0.001 |
| Emicizumab post-switch | 37.8 (33; 44.5) | 0.0 (0.0; 0.0) | 0.0 (0.0;0.0) | 28 (70) P <0.001 |
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| * n=5 with mixed rFVIII and rFVIIIFc during the study period were not included in the sub-analysis by factor replacement type † follow-up periods pre and post matched to median 36 weeks for comparison of bleed-free rates |
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Within-person analysis of emicizumab with prior prophylaxis
Significant reductions in Haemtrack reported bleeding events were observed after changing to emicizumab prophylaxis in UK clinical practice. The safety profile appears acceptable but ongoing pharmacovigilance is required to determine long-term outcomes.
To cite this abstract in AMA style:
Wall C, Xiang H, P Palmer B, Chalmers E, Chowdary P, W Collins P, Fletcher S, P Hart D, W Hall G, Liesner R, Shapiro S, Stevensen D, Talks K, RM Hay C, United Kingdom Haemophilia Centre Doctors' Organisation . Efficacy and Safety of Emicizumab Prophylaxis in Severe Haemophilia A without Inhibitors: A Report from the UK Haemophilia Centre Doctors’ Organisation (UKHCDO) [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/efficacy-and-safety-of-emicizumab-prophylaxis-in-severe-haemophilia-a-without-inhibitors-a-report-from-the-uk-haemophilia-centre-doctors-organisation-ukhcdo/. Accessed December 11, 2023.« Back to ISTH 2021 Congress
ISTH Congress Abstracts - https://abstracts.isth.org/abstract/efficacy-and-safety-of-emicizumab-prophylaxis-in-severe-haemophilia-a-without-inhibitors-a-report-from-the-uk-haemophilia-centre-doctors-organisation-ukhcdo/