Abstract Background: Detailed treatment outcomes data in people with congenital hemophilia A (PwHA) outside North America, Western Europe, and Japan are scarce. We report data in children, adolescents, and adults with severe HA with/without factor (F)VIII inhibitors enrolled in RESHAPE across Latin America, Eastern Europe, Africa, Asia, and the Middle East. Methods: RESHAPE was a non-interventional, real-world study conducted across 80 sites in 24 countries. PwHA with FVIII activity 1 IU/dL were enrolled (Sep 2020–Dec 2022) into Cohort A (without FVIII inhibitors) or Cohort B (with inhibitors) and observed for 52 weeks (wks) or until treatment switch. Bleeds were recorded using a Bleed and Medication Questionnaire. We report mean annualized treated bleed rates (ABRs) and participants with zero treated bleeds, per age group (12, 12–17, and ≥18 years yrs), and all adverse events (AEs). Treatment dosing was per label and local practice. Results: Among a total of 669 PwHA, 489 comprised Cohort A: 45 (9.2%) received emicizumab prophylaxis (EMI), 369 (75.5%) FVIII prophylaxis, and 75 (15.3%) FVIII on demand (OD). In Cohort B, among 180 PwHA, 81 (45.0%) received EMI, 51 (28.3%) bypassing agent (BPA) prophylaxis, and 48 (26.7%) BPAs OD. Across age groups in Cohort A, most PwHA received FVIII prophylaxis, followed by FVIII OD and EMI. In Cohort B, most children received EMI, followed by BPA prophylaxis and BPAs OD; most adolescents also received EMI, followed by BPAs OD and BPA prophylaxis; most adults received BPA prophylaxis, followed by BPAs OD and EMI. Mean treatment duration (mTD) for Cohort A/B was 52/47 wks, 48/33 wks, and 40/32 wks for EMI, FVIII/BPA prophylaxis, and FVIII/BPA OD, respectively. In Cohort A, mean (95% confidence interval CI) ABRs (treated bleeds) were lower with EMI (0.2 0–4.1, 0.5 0–4.7, and 0.4 0–4.4 for ages 12, 12–17, and ≥18 yrs, respectively) compared with FVIII prophylaxis (3.5 0.8–9.5, 4.1 1.1–10.3, and 4.9 1.6–11.6, respectively) and FVIII OD (6.3 2.4–13.5, 6.3 2.4–13.5, and 16.5 9.5–26.6, respectively). Similar results were observed in Cohort B: mean (95% CI) ABRs were 0.3 (0–4.3), 0.5 (0–4.7), and 1.2 (0.1–6.0), respectively, for EMI; 8.9 (4.1–17.0), 5.6 (2.0–12.5), and 8.4 (3.7–16.3), respectively, for BPA prophylaxis; and 11.7 (6.0–20.6), 13.4 (7.2–22.7), and 7.9 (3.4–15.7), respectively, for BPAs OD. The proportion of PwHA with zero treated bleeds was higher in participants receiving EMI vs FVIII/BPA prophylaxis and FVIII/BPAs OD. In PwHA aged 12 yrs, respective proportions in Cohort A were 80% (n=16; mTD: 51 wks), 33% (n=43; mTD: 50 wks), and 13% (n=3; mTD: 51 wks) for EMI, FVIII prophylaxis, and FVIII OD. In Cohort B, they were 81% (n=34; mTD: 52 wks), 41% (n=9; mTD: 38 wks), and 5% (n=1; mTD: 45 wks) for EMI, BPA prophylaxis, and BPAs OD. Proportions of PwHA with ≥1 AE were similar across cohorts: 19 (28.8%) for EMI, 124 (33.2%) for FVIII prophylaxis, and 23 (29.9%) for FVIII OD (Cohort A); 33 (31.7%) for EMI, 18 (31.6%) for BPA prophylaxis, 16 (31.4%) for BPAs OD (Cohort B). One thromboembolism occurred in the FVIII prophylaxis group (unrelated to treatment). No thrombotic microangiopathies occurred, nor any indication of anti-emicizumab antibody development. Two deaths were reported in the FVIII prophylaxis group (unrelated to treatment). No AEs led to treatment discontinuation. The most common AEs were infections and infestations (Cohort A/B: 18.2%/14.4%, 13.4%/12.3%, and 9.1%/11.8% with EMI, FVIII/BPA prophylaxis, and FVIII/BPAs OD, respectively); musculoskeletal and connective tissue disorders (4.5%/4.8%, 8.3%/5.3%, and 5.2%/9.8%, respectively); injury, poisoning and procedural complications (4.5%/8.7%, 5.9%/14.0%, and, 3.9%/7.8%, respectively); and gastrointestinal disorders (0%/3.8%, 5.1%/8.8%, and 6.5%/7.8%, respectively). Conclusions: These results provide critical real-world evidence from regions with scarce treatment-outcomes data. Although most participants received prophylaxis, a substantial proportion were treated OD, suggesting that while prophylaxis is viable in these regions, there is a remaining need to expand its use. Consistently across age groups, bleeding rates were lowest with EMI prophylaxis, followed by FVIII/BPA prophylaxis and FVIII/BPAs OD; despite this, EMI use was low, particularly in the non-inhibitor population, suggesting barriers to access in the studied regions. All treatments were well tolerated and consistent with published safety data.
Lemos et al. (Mon,) studied this question.