PB0259 - Relationship between current and historic clinical characteristics and bleeding outcomes in people with severe Haemophilia A on emicizumab: a multivariate analysis of data from the CHESS studies

Background: Past medical history and clinical characteristics of people with severe haemophilia A (PwSHA) can affect current therapy outcomes. This is a crucial element to consider evaluating treatment effectiveness in a shifting therapeutic landscape.

Aims: This analysis evaluated the impact of historic and current clinical characteristics on the bleeding outcomes in a population of PwSHA receiving emicizumab.

Methods: Data on non-inhibitor PwSHA, receiving emicizumab for ≥12 months, were examined from the CHESS data platform (2019-2022) (a repeated European cross-sectional retrospective burden-of-illness study conducted in adult PwH). A negative binomial regression model was specified to test and quantify the effect of historic clinical covariates on annual bleeding rate (ABR). ABR was defined as the sum of major and minor bleeding events in the preceding 12 months. A sensitivity analysis assessed spontaneous ABR (ASBR). Results are presented as mean (SD) and regression estimates (i.e. average marginal effects, AME).

Results: Among the 131 PwSHA included, age was 36.1 years (15.2) and BMI was 25.1 (3.1). Documented ABR was 3.1 (2.7) pre-switch to emicizumab and 1.7 (2.2) post-switch. Pre-switch ABR was a significant predictor of post-switch ABR (p < 0.001), with AME of 0.11 associated with each pre-switch bleeding event (Table 1). Pre-switch ABR remained a significant predictor in ASBR sensitivity analysis, with AME of 0.16 (p < 0.001) with each additional pre-switch bleeding event. Chronic joint damage also demonstrated a notable impact on ABR, with AME of 0.25 (p < 0.05) for each additional problem joint (Table 2).

Conclusion(s): These findings suggest an influence of historic bleeding and chronic joint damage on current bleeding patterns for PwSHA on emicizumab. ABR and ASBR were related to historic bleeding rates, while ASBR also appeared to be influenced by chronic joint damage. Early in life reduced bleeding frequency and prevention of chronic joint damage may be beneficial in minimising future bleeding and joint deterioration.