Background: Advances in hemophilia A (HA) treatment have led to lower bleeding rates (Srivastava et al. Haemophilia 2020), shifting focus toward functional endpoints such as joint health. Despite treatment with factor (F)VIII prophylaxis, joint health has been observed to deteriorate over time (Arvanitakis et al. Haemophilia 2024). BEYOND ABR (NCT05181618) aims to evaluate joint health and physical activity outcomes in people with HA (PwHA) switching from FVIII prophylaxis to emicizumab. This second interim analysis reports data analyzed after 12 months of treatment with emicizumab.

Methods: BEYOND ABR is a Phase IV, multicenter, open-label study in PwHA aged 13–69 years with moderate/severe HA without FVIII inhibitors. Joint health for ankles, knees, and elbows is evaluated in participants' joints without pre-study surgery/procedures using the Hemophilia Joint Health Score (HJHS) 2.1. Numerical changes in problem joint counts (defined as per Chowdary et al. Haemophilia 2023) from baseline are captured by both participants and investigators. Target joint resolution is assessed in participants with ≥52 weeks of follow-up. Physical activity is measured using the International Physical Activity Questionnaire (IPAQ). The number of participants with zero treated bleeds is determined using data from a Bleeds and Medication Questionnaire. The Emicizumab Preference Survey was carried out following 6 months of emicizumab treatment.

Results: Overall, 136 PwHA were enrolled, all male with varying levels of joint status/impairment. At the single joint level, mean (standard deviation [SD]) HJHS total score was 2.3 (3.5) at baseline and improved by -0.3 (1.7) at Month 6 and -0.5 (1.9) at Month 12. At Month 6, 93/726 (12.8%) joints showed an improvement of ≥2 points, increasing to 119/696 (17.1%) at Month 12; 41/726 (5.6%) joints and 42/696 (6.0%) joints showed a worsening of ≥2 points at Month 6 and Month 12, respectively.

At the participant level, the mean (SD) HJHS sum of joints (excluding Global Gait Score; maximum score: 120, calculated as 6 joints x 10 points each) was 10.1 (13.2) at baseline and improved by -2.0 (6.4) at Month 6 and -2.8 (7.9) at Month 12. In total, 23/88 (26.1%) participants reported an improvement of ≥4 points in HJHS sum of joints from baseline to Month 12 and 5/88 (5.7%) reported worsening of ≥4 points at Month 12.

At Month 12, the number of participant-reported problem joints had decreased from baseline in 35/117 (29.9%) participants, including resolution of ≥2 problem joints in 16 (13.7%) participants. Conversely, 16/117 (13.7%) participants reported an increase in the number of problem joints from baseline, including an increase of ≥2 problem joints in 8 participants (6.8%). The number of investigator-reported problem joints reduced in 33/131 (25.2%) participants at Month 12; 13 (9.9%) participants had ≥2 resolved problem joints. Overall, 19/131 (14.5%) participants had an increase in investigator-reported problem joints, including 14 (10.7%) with an increase of ≥2 problem joints. In participants who remained in the study for at least one year, 27/27 (100%) baseline target joints in 15 participants had resolved at Month 12.

In participants with valid IPAQ data at baseline and/or 3 months and/or 12 months after switching to emicizumab, the proportion of participants in the low physical activity category decreased from 30.8% (32/104) at baseline to 22.3% (23/103) at Month 3, and remained stable at Month 12 (23.4% [22/94]). The proportion of participants in the high physical activity category increased from 44.2% (46/104) to 52.4% (54/103) at Month 3, and was 50.0% (47/94) at Month 12.

Zero treated bleeds were reported by 110/136 (80.9%) participants between Weeks 1 and 24, and 105/134 (78.4%) between Weeks 25 and 48.

At Month 6, 125/130 (96.2%) participants preferred emicizumab to their previous FVIII prophylaxis, while only 1/130 (0.8%) preferred their previous treatment; 4/130 (3.1%) had no preference.

Conclusions: In the first 12 months after switching from FVIII prophylaxis to emicizumab, participants had low bleeding rates associated with numerical improvements in joint health, as measured with HJHS, plus a reduction in the number of problem and target joints. Overall, physical activity levels assessed with IPAQ were stable or showed a shift towards higher activity levels, and most participants preferred emicizumab compared with their previous treatment. Follow-up will continue for 3 years.

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2025
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