Quinn Jennifer, Delaney Kathleen A, Wong Wing Yen, Miesbach Wolfgang, Bullinger Monika
BioMarin Pharmaceuticals UK Ltd, London, UK.
BioMarin Pharmaceutical Inc., Novato, CA, USA.
Patient Relat Outcome Meas. 2022 Jul 18;13:169-180. doi: 10.2147/PROM.S357555. eCollection 2022.
The hemophilia-specific health-related quality of life (HRQOL) questionnaire (Haemo-QOL-A) is validated for detecting QOL changes following standard therapy for hemophilia A, but has not been rigorously evaluated after gene therapy. This post hoc analysis evaluated the psychometric properties of Haemo-QOL-A in adult people with severe hemophilia A (PWSHA) receiving valoctocogene roxaparvovec (AAV5-hFVIII-SQ) in 2 clinical trials (phase 1/2, NCT02576795; phase 3, NCT03370913).
Adult PWSHA (factor VIII levels ≤1 IU/dL) received 1 AAV5-hFVIII-SQ infusion (6×10 vg/kg). Participants were assessed using the Haemo-QOL-A and the EuroQOL (EQ)-5D-5L and visual analog scale (VAS) questionnaires pre- and post-infusion. Psychometric analyses included convergent and discriminant validity, internal consistency, and reliability. Clinically important difference (CID) was estimated using 3-point change in EQ-5D-5L VAS as anchor.
Haemo-QOL-A data were analyzed from 7 (phase 1/2, 3-year follow-up) and 16 participants (phase 3, 26-week analysis). Change in Haemo-QOL-A Total Scores correlated with EQ-5D-5L VAS score change at 26 weeks (Pearson's correlation 0.77). At 26 weeks, increased Haemo-QOL-A Physical Functioning was associated with decreased EQ-5D-5L Pain and Discomfort and decreased Anxiety and Depression (Spearman's Rank correlations -0.73 and -0.62, respectively, <0.01). Internal consistency analysis showed good reliability for all domains (Cronbach's alpha >0.7) except Treatment Concern (Cronbach's alpha = 0.31). Anchor-based CID estimates were met for Haemo-QOL-A Total Score (≥5.5) and domain scores (≥6) for Consequences of Bleeding, Physical Functioning, Role Functioning, and Worry.
Our preliminary results suggest that the Haemo-QOL-A is a valid, reliable instrument for HRQOL assessment in PWSHA undergoing gene therapy. Future research should be undertaken to confirm these findings in a larger number of participants.
血友病特异性健康相关生活质量（HRQOL）问卷（Haemo-QOL-A）已被验证可用于检测A型血友病标准治疗后的生活质量变化，但尚未在基因治疗后进行严格评估。这项事后分析评估了Haemo-QOL-A在两项临床试验（1/2期，NCT02576795；3期，NCT03370913）中接受valoctocogene roxaparvovec（AAV5-hFVIII-SQ）治疗的重度A型血友病成年患者（PWSHA）中的心理测量特性。
成年PWSHA（因子VIII水平≤1 IU/dL）接受1次AAV5-hFVIII-SQ输注（6×10 vg/kg）。在输注前和输注后使用Haemo-QOL-A、欧洲生活质量量表（EQ）-5D-5L和视觉模拟量表（VAS）问卷对参与者进行评估。心理测量分析包括收敛效度和区分效度、内部一致性和可靠性。以EQ-5D-5L VAS的3分变化为锚点估计临床重要差异（CID）。
对7名参与者（1/2期，3年随访）和16名参与者（3期，26周分析）的Haemo-QOL-A数据进行了分析。Haemo-QOL-A总分的变化与26周时EQ-5D-5L VAS评分的变化相关（Pearson相关性为0.77）。在26周时Haemo-QOL-A身体功能的改善与EQ-5D-5L疼痛与不适的减轻以及焦虑和抑郁的减轻相关（Spearman等级相关性分别为-0.73和-0.62，<0.01）。内部一致性分析显示，除治疗关注（Cronbach's alpha = 0.31）外，所有领域的可靠性都很好（Cronbach's alpha>0.7）。Haemo-QOL-A总分（≥5.5）以及出血后果、身体功能、角色功能和担忧等领域得分（≥6）达到了基于锚点的CID估计值。
我们的初步结果表明，Haemo-QOL-A是评估接受基因治疗的PWSHA的HRQOL的有效、可靠工具。未来应开展研究，在更多参与者中证实这些发现。
