Interim bleeding data of 522 hemophilia A patients from the international AHEAD Study after 3 years of observation

K. Steinitz-Trost1, J. Oldenburg2, D. A. Tsakiris3, C. Hermans4, K. Khair5, R. Liesner5, M. G. Mazzucconi6, G. Spotts7, A. J. Reininger1, A. Gringeri1 (1Vienna, Austria, 2Bonn, Germany, 3Basel, Switzerland, 4Brussels, Belgium, 5London, United Kingdom, 6Rome, Italy, 7Westlake Village, USA)

Bleeding disorders, coagulation and fibrinolytic factors
Date: 17.02.2017,
Time: 17:15 - 18:15

Objective: Continuous long-term real-world data on treatment outcome and safety in a large cohort of hemophilia A patients are still insufficient.

Methods: The AHEAD study is a non-interventional, prospective long-term cohort study including severe and moderate hemophilia A patients treated with ADVATE. Study endpoints include long-term joint health outcomes, annualized (joint) bleeding rates (ABR/AJBR), factor consumption, quality of life and safety data. This report includes data from 3 years of follow up.

Results: Interim report includes data from 522 patients from 21 countries (German sister study is not included), for overall 1,160 patient years. Of these, 334 patients completed year 1, 238 year 2 and 136 year 3 study visits. Median age at screening was 17 years (min-max: 0 – 78) and 57% of patients had severe HA (FVIII<1%); the majority was on prophylaxis. The median ABRs in year 1, 2 and 3 were 1.2/1.2/1.9 respectively in patients on prophylaxis and 8.4/10.0/7.2, respectively in patients on OD. Median AJBRs were 0.9/0.9/1.0 in the prophylaxis group and 6.4/5.5/5.9 for patients on OD in the first three years of observation. Very similar data were reported taking only severe hemophilia A patients on prophylaxis into account. . Moreover, about 44% of patients on prophylaxis vs. 23% of patients on on-demand had zero annual joint bleeding rates (AJBR).Effectiveness of prophylaxis assessed by investigators was excellent/good in 93-96% of cases in the three years of observation. Functionality assessment using the hemophilia activity level (HAL) questionnaire showed a median summary score of 77.3-86.7 for patients on prophylaxis and 67.9-71.3 in patients OD over the 3 year follow up period. Health related quality of life (HRQoL) assessment showed differences in the domain physical functioning (median score of 75-100 in patients on prophylaxis vs. 50-75 on OD) and role physical (median scores of 75 vs. 62.5-75 in patients on prophylaxis and OD, respectively). Nine patients developed inhibitors that all disappeared spontaneously.

Conclusion: Interim read-out of 3 year follow up of patients enrolled in the AHEAD study show a clinically meaningful difference in ABR/AJBR, HAL, HRQoL of patients on prophylaxis or OD treatment. These data also confirm that the goal of zero bleeds is achievable, although not yet achieved in all patients.