Validation of a new instrument to measure disease-related distress among patients with haemophilia.

INTRODUCTION: In patients with haemophilia, general psychological distress as measured by the National Comprehensive Cancer Network (NCCN) distress thermometer has been associated with pain, disability and increased healthcare utilization. AIMS: To develop and validate a measure of haemophilia-related distress. METHODS: After qualitative interviews, the Hemophilia-Related Distress Questionnaire (HRDq) was developed. To validate the HRDq, adults (≥18 years) with haemophilia were enrolled, reported demographic and clinical information, and completed the HRDq and other questionnaires that measured similar constructs. Analysis included factor analysis and assessment of internal consistency using Cronbach's α, convergent validity using Pearson's correlation coefficient, and discriminant validity by comparing subgroups of patients. Test-retest reliability was assessed using an intraclass correlation coefficient (ICC). RESULTS: Among 130 enrolled participants, 126 (median age=32.7 years) completed the 24 item HRDq in a median time of 5.4 minutes with overall HRDq scores ranging from 2 to 83 (median score=31.5; higher scores indicating higher distress). Assessment of convergent validity demonstrated a strong correlation (ρ>.60) of the HRDq total score with the NCCN Distress Thermometer, Haem-A-QoL total Score, and PROMIS-29 Profile social role domain and a mild to moderate correlation with all other questionnaire domains (.3-.59, p < .05). Distress was higher among those who had less education, were not employed, and were disabled and was not significantly different among those with severe compared with non-severe disease. Assessment of test-retest reliability demonstrated an ICC value of .84 (95% CI .71-.91) for the total score. CONCLUSIONS: The HRDq demonstrates good internal consistency, construct and discriminant validity, and retest reliability with a low responder burden.

Emicizumab for hemophilia A without inhibitors.

Introduction: Hemophilia A (HA) is an inherited bleeding disorder that, if not properly treated, is associated with debilitating joint damage due to recurrent hemarthroses as well as life-threatening bleeds including intracranial hemorrhage. For decades, the only method to prevent bleeding events was to infuse factor (F) VIII concentrates intravenously two to three times weekly. Although successful in reducing bleeding frequency, preventing a high proportion of joint disease, and extending life expectancy, standard continuous prophylaxis with FVIII is burdensome and insufficiently effective at preventing long-term joint dysfunction in some patients. In October 2018, the Federal Drug Administration approved a novel agent, emicizumab-kxwh, for the treatment of patients with HA without inhibitors. Areas covered: In this article, the preclinical and clinical development of emicizumab-kxwh will be reviewed. Data from licensure phase 3 clinical trials will be reviewed in detail discussing issues of both safety and efficacy. Expert opinion: As emicizumab-kxwh leads the way of a shift in treatment paradigm for patients with HA without inhibitors, a number of questions remain, including the impact of emicizumab-kxwh on joint and bone health, inhibitor development, and thrombotic risk. Ultimately, time and clinical investigation will be able to elucidate the influence of emicizumab-kxwh in these areas.