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.

Plain language summary

Effectiveness and safety of octocog alfa and rurioctocog alfa pegol to treat hemophilia A in the real world

Hemophilia A is a rare inherited condition in which the blood of a patient does not clot properly. Over time, bleeding into joints such as the knees and elbows can cause severe damage, leading to pain and reduced mobility. Octocog alfa and rurioctocog alfa pegol are treatments for hemophilia that can be used when needed to stop bleeding (“on-demand treatment”) and can also be taken regularly to prevent future bleeds (“prophylaxis”). Clinical trials have shown that these treatments are effective, but it is important to know if the treatments work just as well when they are used in the real world. In the German AHEAD study, we looked at the effectiveness and safety of octocog alfa and rurioctocog alfa pegol in patients with hemophilia A who were prescribed treatment by their doctor. The joint health of patients was measured using the Gilbert scale, which takes into account pain, bleeding, and examination of the joint by the doctor. Over time, Gilbert scores improved, particularly for patients who received prophylaxis rather than on-demand treatment. Similarly, the number of bleeds patients experienced per year tended to be lower in those receiving prophylaxis rather than on-demand treatment, although this German ADVATE / ADYNOVI Hemophilia A Outcome Database (AHEAD) study only applied for patients with severe hemophilia. In those with moderate hemophilia, the number of bleeds per year was similar with prophylaxis and on-demand treatment. The safety of octocog alfa and rurioctocog alfa pegol was similar to what has previously been seen in clinical trials. Overall, the results from this study show that octocog alfa and rurioctocog alfa pegol are as effective for managing hemophilia A in the real world as they are in clinical trials, particularly when given as regular prophylaxis to prevent bleeding.

Graphical Abstract