Final data from the German AHEAD study: effectiveness and safety of octocog alfa and rurioctocog alfa pegol for hemophilia A in a real-world setting

Background: Octocog alfa and rurioctocog alfa pegol have demonstrated efficacy in the prevention and management of bleeding associated with hemophilia A (HA) in clinical trials. The German AHEAD study (DRKS00000556) was designed to provide real-world data over a long period to complement these studies. Objectives: To assess real-world long-term outcomes in patients with moderate/severe HA receiving octocog alfa or rurioctocog alfa pegol in routine clinical practice Design: Noninterventional, prospective, study conducted between 2010 and 2022. Methods: The primary endpoint was the incidence of hemophilia-affected joint arthropathy. Secondary endpoints included annualized bleeding rate and joint bleeding rate (ABR/AJBR), and octocog alfa and rurioctocog alfa pegol consumption. Final data are presented. Results: The analysis included 377 patients aged 1–80 years who received octocog alfa (severe HA, n = 309; moderate HA, n = 68) and 99 patients aged ⩾12 years who received rurioctocog alfa pegol (severe, n = 82; moderate, n = 17). Over 8 years of follow-up, average Gilbert scores were maintained with prophylaxis. In patients with severe HA, median ABRs/AJBRs were generally lower with prophylaxis versus on-demand treatment, whereas in moderate HA, bleeding rates were similar. Treatment-related adverse events (AEs) and serious treatment-related AEs were reported in 5.3% and 4.2% (35 events including hemorrhage, arthropathy, and factor FVIII (FVIII) inhibitor development) of patients receiving octocog alfa, respectively, and 5.1% and 4.0% of patients receiving rurioctocog alfa pegol, respectively. One previously treated patient receiving octocog alfa developed de novo FVIII inhibitors. Conclusion: These real-world data corroborate previous clinical trial and real-world data demonstrating the long-term effectiveness and safety of octocog alfa and rurioctocog alfa pegol in patients with HA. In patients with severe HA, octocog alfa prophylaxis was associated with reduced bleeding rates compared with on-demand therapy. Trial registration: Deutsches Register Klinischer Studien (German Clinical Trials Register): DRKS00000556.