Real-World Patient-Reported Sickle Cell Disease Burden in the United States
Authors: Barcelos Giovanna Tedesco , Colavecchia Carmine , Meier Emily Riehm , Wirz Reto , Hines Dionne M. , Purdie David M. , Libby Susanna , Iqbal Halima , Lai Sophie , Chatterton Emma , Mellor Jennifer , Baker Christine L. 
Published: December 2024

Introduction: Sickle cell disease (SCD) is an inherited blood disorder caused by a β-globin gene mutation producing sickle Hb (HbS). HbS polymerization causes red blood cell sickling, leading to hemolysis, anemia, vaso-occlusive crises (VOCs), and cumulative organ damage. Clinical manifestations of SCD are burdensome and can reduce the health-related quality of life (HRQoL) of affected individuals. Evidence characterizing the patient-reported burden of SCD using validated patient-reported outcome (PRO) measures and associated Hb (hemoglobin) values is limited. We investigate patient perspectives on SCD burden and impact on HRQoL, fatigue, pain, and work productivity leveraging PRO measures.
Methods: Analyses utilized data from an Adelphi Real World self-reported patient survey collected in the United States between June and July of 2024. Adults living with SCD completed questionnaires about their demographics, SCD burden and PRO measures, including the EQ-5D-5L and EQ-5D visual analog scale (VAS), the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue scale, and Work Productivity and Activity Impairment (WPAI) measures. Participants rated their HRQoL using the EQ-5D (score range, 0-1; 0=‘state as bad as being dead’ to 1='full health') and EQ-VAS (0-100; 0='worst health imagined' to 100='best health imagined') and the 13-item FACIT-Fatigue PRO (0-4; 0='not at all fatigued' to 4=‘very much fatigued’ with a total score of 0-52). Higher WPAI scores indicate greater impairment and less productivity. Participants were also asked their baseline Hb value. All analyses were descriptive.
Results: Of the 71 survey participants with baseline Hb levels, the mean (SD) age was 37.3 (10.4) years, 94% were Black, 92% were female, and 41% were employed. Overall, the mean (SD) self-reported baseline Hb level was 7.3 (1.9) g/dL; 37% of individuals had a Hb of &lt;7 g/dL (low Hb), 34% had ≥7-&lt;9 g/dL (mid Hb), and 30% had ≥9 g/dL (high Hb). Approximately 69% of participants in the low Hb group, 54% in the mid Hb group, and 43% in the high Hb group reported ≥4 VOCs in the last 12 months. All participants in the low and mid Hb groups reported ≥1 VOC and 19% in the high Hb group reported no VOCs in the prior 12 months.
In the low Hb group, 100% of respondents required caregiver assistance with activities of daily living (ADLs) compared with 86% in the mid and 90% in the high Hb groups. For the worst pain experienced in the 7 days prior to survey completion, 100% of the low Hb group reported pain compared with 92% and 76% in the mid and high Hb groups, respectively. Experiencing ‘very severe’ pain in the prior 7 days was reported by 35% of participants in the low, 21% in the mid, and 5% in the high Hb groups, respectively.
The mean (SD) EQ-5D VAS scores for those in the lowest to the highest Hb groups were 62.0 (22.4), 63.6 (21.5) and 67.0 (20.2), respectively. The median (interquartile range, IQR) FACIT-Fatigue score for individuals in the low Hb group was 23.5 (16.8-35.2), and in the mid and high Hb groups it was 26.0 (19.2-37.2) and 24.0 (19.5-31.5), respectively. Of those in the low Hb group, 23% selected ‘very much’ for 'I feel weak all over,' while 12% and 5% of the mid and high Hb groups reported the same. In the low Hb group,19% of participants chose 'very much' for 'need to sleep during the day,' compared with 12% and 5% in the mid and high Hb groups. No one in the high Hb group responded, 'very much' to 'feeling 'too tired to eat,' whereas 8% each in the low and mid Hb groups did.
The median (IQR) WPAI score was 40.0 (20.0-66.2) for participants who reported working (n=35). For activity impairment, the median score for the low Hb group (n=26) was 60 (50.0-80.0), and in the mid (n=24) and high Hb (n=21) groups it was 60 (32.5-67.5) and 50.0 (15.0-70.0), respectively.
Conclusions: Respondents with SCD and low Hb levels self-reported a greater SCD burden; they required more assistance with ADLs, have higher pain intensity, higher VOC frequency, and worse PRO scores than those in mid and high Hb groups. Numerical differences were noted in the FACIT-Fatigue domains; respondents with low Hb levels reported more fatigue, but the overall scores were similar across Hb groups. Maintaining higher Hb levels may lead to a lower burden of disease and improve HRQoL for patients with SCD.