Emicizumab in Management of Hemophilia_A Patients with High Titer FVIII Inhibitor - Real-World Evidence from Poland

Background: Since 2020, under the National Hemophilia Treatment Program (outside of clinical trials), emicizumab has been used to manage Polish patients with hemophilia A with factor VIII (FVIII) inhibitor (PWHAinh). Emicizumab's efficacy and safety real-world data have been recently reported but more data are needed to better understand the role of emicizumab.

Aim: To evaluate the efficacy and safety of emicizumab in 34 adults with PWHAinh.

Methods: We calculated annualized bleeding rates requiring hemostatic therapy (ABR-HT) during emicizumab prophylaxis and compared these with ABR-HT in the pre-emicizumab period. The retrospective analysis included data from the 6 months pre-emicizumab prophylaxis. These data were collected from Hemophilia Treatment Centers in Poland. Physicians entered the data from patients' medical records into a specifically designed electronic case report form (eCRF). Statistical calculations presented in this paper were performed using STATISTICA version 13.

Results: Thirty-four men with PWHAinh, aged 21-70 (median: 41) years were included. The mean maximum inhibitor titer was 678.7 ± 1462.2 (median: 123, range: 3 to 5940) BU/mL.

ABR was 24 in the pre-emicizumab period, and 0.28 during emicizumab treatment (p < 0.0001).

Only 1/34 (2.9%) patients declared no comorbidities. Of the remaining patients, 94% reported hemophilic arthropathy. Approximately 62% had a history of life-threatening bleeding.

Twenty-two patients (64.7%) received long-term prophylaxis in the 6 months preceding emicizumab treatment; 19/22 (86.4%) received activated prothrombin complex concentrate (aPCC), 2/22 (9.1%) received recombinant factor VIIa (rFVIIa), and 1/22 (4.5%) received aPCC and rFVIIa.

In the 6 months before emicizumab was introduced, 30/34 (88.2%) of all patients and 18/22 (81.8%) of those receiving long-term prophylaxis reported bleeding episodes that required hemostatic therapy. In total, 12.073.509 aPCC units and 8.308 mg rVIIa were used for the bleeding treatment and prophylaxis of 34 patients.

Immediately before introducing emicizumab, patients had a mean 1.47 ± 1.86 (median: 1) target joints (target joint = joints with a minimum of 3 bleeds in the last 6 months).

Mean duration of emicizumab treatment for all patients was 1.6 ± 2 (median: 1) years; 10/34 (29.4%) had started emicizumab in clinical trials and continued treatment in the National Hemophilia Treatment Program.

At the start of emicizumab therapy, mean patient weight was 80.1 ± 14.2 (median: 80.0) kg. After the saturating dose period, 21/34 (61.8%) received emicizumab at 3 mg/kg every fortnight and 11/34 (32.4%) received 1.5 mg/kg once a week. Only 2/34 (5.9%) received 6 mg/kg once a month.

During emicizumab therapy, the dosing regimen was changed for 3/34 (8.8%) patients because of body weight changes.

No emicizumab-related adverse events were observed. During emicizumab treatment, 7/34 patients (21%) experienced breakthrough bleeds, of whom 5/7 (71.4%) required hemostatic therapy (all received 237 mg rFVIIa in total). Spontaneous bleeds and traumatic bleeds were observed in 2 and 6 patients, respectively (1 patient had both types of bleeds). Six/34 (17.6%) patients underwent various minor invasive interventions, including colonoscopy and gastroscopy, tooth extractions, and other small surgical procedures, of which 4/6 (66.7%) received 77 mg rFVIIa.

At the time of data analysis, all 34 patients were continuing emicizumab therapy.

Conclusion: Emicizumab significantly reduced ABR vs. previously used by-passing agents (rFVIIa and aPCC) and showed a favorable safety profile with no concerns. Only 8.8% of patients needed their dose of emicizumab adjusted due to body weight changes.

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