Improvement in Annualized Bleed Rate in Patients with Hemophilia A Initiating Emicizumab - Physician Reported Outcomes from the Adelphi Hemophilia a Disease Specific Programme™

Introduction: Emicizumab is indicated for prophylaxis to prevent or reduce the frequency of bleeding episodes in patients with hemophilia A (PwHA) with or without factor VIII inhibitors. There is a paucity of research on real-world effectiveness of emicizumab in PwHA, particularly in non-severe hemophilia A (HA). We aimed to describe characteristics of PwHA initiating emicizumab, and examine the change in annualized bleed rate (ABR) in these patients after initiating emicizumab in the real world.

Methods: Data were collected via the Adelphi HA Disease Specific Programme™, a point-in-time survey of physicians treating PwHA collected in the United States of America from February 2020 - April 2021. Participating physicians completed a patient record form for their next consulting eligible HA patients using information from their medical charts and physician recall. Data on socio-demographics, clinical characteristics and HA treatment were collected. The sample included patients receiving emicizumab and had been receiving it for at least 12 months at the time of survey completion with the index date defined as the date of emicizumab initiation. The analysis was restricted to patients with complete data on bleeding events in the 12 months before and ≥12 months after emicizumab initiation. We calculated the annual bleed rate in the pre-index period, and annualized the bleed rate in the post-index period for those with >12 months follow-up. Change in proportion of patients with zero bleeds pre- and post-emicizumab was evaluated using the McNemar test. Changes in ABR over time in the overall cohort and subgroups of disease severity (severe vs. mild/moderate) and inhibitor status were examined using unadjusted negative binomial regression models.

Results: A total of 19 patients, 14 (74%) severe and 5 (26%) mild/moderate met the inclusion criteria. 18 patients were adult (95%) with a mean age of 31 (standard deviation [SD] = 11.5) years; 15 (79%) patients were white, 8 (42%) patients had active inhibitors at the time of survey completion [5 (36%) of the 14 severe, and 3 (60%) of the 5 mild/ moderate patients], 14 (74%) patients previously received prophylactic treatment, 14 (74%) patients were commercially insured and 12 (63%) patients received at least some care at a Hemophilia Treatment Centre. Mean age at diagnosis was 4.1 (SD=8.9) years; 13.9 (SD=12.2) years in mild/ moderate patients, and 0.1 (SD=0.27) years for severe patients. The most common comorbidities were hypertension (n=3, 16%), anxiety (n=2, 11%) and depression (n=2, 11%). The average time since starting treatment with emicizumab was approximately 20.8 (SD=7.0) months. A larger proportion of patients experienced zero bleeds in the post-emicizumab compared to pre-emicizumab period (79% vs. 21%, p=0.003).The ABR was 2.10 events (95% confidence interval [CI]: 1.22 -2.99) before initiating emicizumab compared to 0.29 events (95% CI: 0.02 - 0.56) in the post-emicizumab period, indicating an 86% lower ABR after initiating emicizumab prophylaxis (ABR rate ratio [RR]: 0.14; 95% CI: 0.06 - 0.34; p<0.001). In the pre-emicizumab period, the ABR in severe patients was 1.71 events (95% CI: 0.72 -2.70) and 3.2 events (95% CI: 1.63 - 4.77) in mild/moderate patients compared to 0.19 events (95% CI: -0.08 - 0.47) and 0.57 events (95% CI: -0.09 - 1.22) respectively, in the post-emicizumab period, suggesting an 89% (ABR RR: 0.11; 95% CI: 0.03 - 0.40; p=0.001) and 82% (ABR RR: 0.18; 95% CI: 0.05 - 0.63; p=0.007) lower ABR in these subgroups respectively, after initiating emicizumab. Similarly, the ABR in patients with active inhibitors was 2.13 events (95% CI: 0.81 - 3.44) and 2.09 events (95% CI: 0.9 - 3.28) in patients without inhibitors in the pre-emicizumab period compared to 0.21 events (95% CI: -0.25 - 0.66) and 0.35 events (95% CI: 0.00 - 0.71) respectively, in the post-emicizumab period, suggesting a 90% (ABR RR: 0.10; 95% CI: 0.02 - 0.48; p=0.004) and 83% (ABR RR: 0.17; 95% CI: 0.06 - 0.50; p=0.001) lower ABR in these subgroups respectively, after initiating emicizumab.

Conclusion: This real-world survey is one of the first to examine the change in ABR in PwHA initiating emicizumab. Significant bleed reductions were seen after initiating emicizumab, regardless of patient's inhibitor status.