Frequency of Vaso-Occlusive Crises Is Associated with Health-Related Quality of Life in Pediatric Patients with Sickle Cell Disease: US Cross-Sectional Surveys of Adolescents and Caregivers

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▪Introduction: Pediatric patients with sickle cell disease (SCD) experience considerable disease-related burden. SCD-related morbidity is characterized by vaso-occlusive crises (VOCs), which are acutely painful events that may cause chronic and potentially life-threatening complications, contributing to the early mortality associated with SCD. Two cross-sectional observational surveys were fielded to evaluate the relationship between VOC frequency and health-related quality of life (HRQoL) in pediatric patients with SCD in the United States (US).Methods: Surveys were administered in 2 populations: adolescents with SCD ages 12-17 years (n=247) and caregivers (n=167) of children with SCD ages 2 months-11 years in the US. Adolescent participants first provided assent to participate, and their guardians provided permission. Adolescents then completed an online survey that included the Child Health Questionnaire-Child Form 45 (CHQ-CF45) and the Adult Sickle Cell Quality of Life Measurement Information System (ASCQ-Me) pain and sleep impact domains. After providing informed consent, caregivers completed an online survey assessing the HRQoL of their child with SCD; survey content was tailored to the age of their child. Caregivers of children ages 5-11 completed the CHQ-Parent Form 50 (CHQ-PF50) and the Patient-Reported Outcomes Measurement Information System (PROMIS) pain interference and sleep disturbance short forms (8a and 4a, respectively). Caregivers of children <5 completed the Infant/Toddler Quality of Life Questionnaire-Short Form 47 (ITQOL-SF47). Children were stratified according to the number of VOCs they experienced in the past 12 months (0-2 VOCs; ≥3 VOCs), and a series of general linear models were conducted to examine the relationship between VOC frequency and HRQoL domain scores, with children's age included as covariate. Statistical significance was evaluated using a significance level of 0.05; p-values were also compared to a Benjamini-Hochberg adjusted critical value.Results: In adolescents ages 12-17, higher frequencies of VOCs were associated with lower HRQoL: adolescents with more frequent VOCs reported greater impacts than adolescents with less frequent VOCs across all domains of HRQoL measured by the CHQ-CF45, including general health, physical functioning, role/social limitations, mental health, and family activities (p<0.05 for all) (Table 1). Pain and sleep (ASCQ-Me domains) were also associated with VOC frequency: greater impacts were observed among adolescents with more frequent VOCs (p<0.001 for both). Similar to adolescents, children < 12 who experienced more frequent VOCs exhibited lower HRQoL as reported by caregivers on most CHQ-PF50 and ITQOL-SF47 domains except those related to behavior and the ITQOL-SF47 change in health domain (Table 2). Children with more frequent VOCs also experienced greater pain interference and sleep disturbance than those with less frequent VOCs (p<0.01 for both PROMIS domains; Table 2). Among caregivers of children ages 5-11, those whose children experienced more frequent VOCs reported greater impacts on CHQ-PF50 parental time/emotions and family activity domains than those whose children experienced less frequent VOCs (p<0.01 for all; Table 2). Caregivers of children ages 2 months-4 years also reported a similar association between VOC frequency and the ITQOL-SF47 parental time domain (p<0.01; Table 2). ITQOL-SF47 parental emotional impact scores also differed when compared to a significance level of 0.05, but were not statistically different after adjusting for multiple comparisons.Conclusions: Via both self- and caregiver-reports, these surveys demonstrated significant detrimental impact of VOCs on pediatric patients with SCD. Decrements were observed across various domains of HRQoL, including general health, physical functioning, pain, sleep, role/social limitations, and mental health. VOC frequency negatively impacted family activities and caregiver time and emotions, confirming anecdotal evidence that the effects of VOCs extend beyond the child to the caregiver. Given the cross-sectional study design, these analyses did not establish a temporal or causal relationship between VOCs and HRQoL; however, it is plausible that treatments aimed at reducing the frequency of VOCs may alleviate some of the burden experienced by pediatric patients with SCD and their families. [Display omitted] DisclosuresCampbell: Novartis Pharmaceuticals Corporation: Consultancy, Research Funding. Rizio: Novartis Pharmaceuticals Corporation: Other: Avery Rizio is employed by QualityMetric Incorporated, LLC, which received funding from Novartis to conduct this research. McCausland: Novartis Pharmaceuticals Corporation: Other: Kristen McCausland is an employee of QualityMetric Incorporated, LLC, which received funding from Novartis to conduct this research. Iorga: Novartis Pharmaceuticals Corporation: Current Employment, Current equity holder in publicly-traded company. Yen: Novartis Pharmaceuticals: Current Employment; Merck & Co., Inc.: Current holder of stock options in a privately-held company, Ended employment in the past 24 months. Paulose: Novartis Pharmaceuticals Corporation: Current Employment. Lee: Novartis Pharmaceuticals Corporation: Current Employment.