Determining meaningful health-related quality-of-life improvement in persons with haemophilia A using the Haemophilia Quality of Life Questionnaire for Adults (Haem-A-QoL)

Introduction The Haem-A-QoL is frequently utilized in haemophilia clinical trials and captures relevant aspects of disease impact. Thresholds for some domains 'Physical Health' (PH), 'Sports & Leisure' (S&L) and 'Total Score' (TS) have previously been identified to benchmark the amount of change that is meaningful to patients, but not been independently confirmed. Aim The objective of this analysis was to determine the clinically important responder (CIR) thresholds for these three domains. Methods CIR thresholds in adult persons with haemophilia A (PwHA) enrolled in HAVEN 1, 3 and 4 studies were determined for improvements from baseline to 24 weeks of emicizumab prophylaxis using anchor-based methodology with the EQ-5D-5L as the validated anchor, cumulative distribution functions (CDF) and distribution-based methodology. The results were compared with previously published thresholds. Results At baseline and after 24 weeks of emicizumab prophylaxis, Haem-A-QoL data from 241/258 patients were available. Concordance was observed between the Haem-A-QoL and EQ-5D-5L in patterns of improvement, deterioration or lack of change. CDF estimates of the Haem-A-QoL PH and TS grouped by response categories on the Mobility, Pain/Discomfort and Usual Activities EQ-5D-5L domains demonstrated the same pattern of responses to each scale; distribution-based estimates were 11.9 for PH, 13.9 for S&L, and 8.3 for TS. Conclusion Our responder thresholds are mostly consistent with those proposed by Wyrwichet al(cut-offs of -10 and -7 for PH and TS, respectively). The majority of responders to emicizumab prophylaxis had improvements greater than the previously reported 10-point reduction in PH and 7-point reduction in TS.