Inhibitors and Obesity: The Prevalence and Strength of Association in People With Haemophilia

INTRODUCTION: Haemophilia is an X-linked bleeding disorder characterized by deficient or defective clotting factors. Obesity in persons with haemophilia (PwH) is associated with joint mobility issues, decreased range of motion and increased target joints. Complications of inhibitors, antibodies that neutralize clotting factor concentrate, can limit physical activity, potentially exacerbating obesity risk. This study examines the association between obesity and inhibitor status in PwH and explores the impact of emicizumab, a bispecific monoclonal antibody, on obesity trends. METHODS: A retrospective cohort analysis of the American Thrombosis and Hemostasis Network ATHNdataset from 2013 to 2021 was conducted. The study included 19,074 males with haemophilia A or B with at least one recorded body mass index measurement. Statistical analyses included logistic regression, generalized estimating equations and difference-in-difference models to assess obesity trends and associations with inhibitors and emicizumab use. RESULTS: Obesity prevalence significantly increased in paediatric and adult PwH (p < 0.001). Children had a significantly increased risk of inhibitors compared to adults with either haemophilia A or B. A history of target joints and emicizumab use was associated with an increased obesity risk. No significant difference in obesity prevalence was found in adult or paediatric PwH with or without exposure to emicizumab. No significant association was observed between obesity and inhibitor status. CONCLUSION: Obesity prevalence in PwH continues to rise, aligning with trends in the general population. The link between target joints and obesity highlights the need to reduce obesity and improve joint health; future studies should explore causality and how physical activity mediates these associations.