Physician-reported impact of vaso-occlusive crises in people with sickle cell disease: A multinational, real-world survey

Abstract Sickle cell disease (SCD) is an inherited red blood cell disorder caused by a β-globin gene mutation producing sickle hemoglobin (HbS). HbS polymerization causes red blood cell sickling, leading to hemolysis, anemia, vaso-occlusive crisis (VOC), and cumulative organ damage. People who experience VOCs due to SCD report severe pain which impacts health-related quality of life and work productivity. Multinational evidence on physician-reported VOC burden in people with SCD is currently limited, and further exploration into the effects of VOC frequency is needed to better understand the clinical management of these patients. We aimed to describe clinical characteristics and treatment patterns in SCD populations who experienced 1, 2, 3, or ≥4 VOCs in the 12 months prior to survey completion. Data were evaluated from the Adelphi Real World SCD Disease Specific Programme, a cross-sectional survey with retrospective data collectionin Brazil, Europe (France, Germany, Italy, Spain, and the United Kingdom), India, the Kingdom of Saudi Arabia, and the United States from August 2024 – April 2025. Physicians reported patient demographics, clinical characteristics including VOCs, and treatment history. The survey was open to the physician's interpretation of the questions. Patients who had received a bone marrow transplant, gene therapy, or voxelotor were excluded from the analysis. Analyses were descriptive. Overall, 307 physicians reported data on 2191 patients. Mean (standard deviation: SD) number of VOCs in the 12 months prior to survey was 1.9 (2.0) with 1615 patients (73.7%) experiencing ≥1 VOC. Of patients experiencing ≥1 VOC, mean (SD) age was 26.5 (12.6) years, 55.9% were male, and 47.8% were Black, African American, or Caribbean. At the time of survey, 29.1% of patients were employed full time (1 VOC: 32.7%; 2 VOCs: 30.0%; 3 VOCs: 25.4%; ≥4 VOCs: 25.4%) and 15.4% were unemployed (1 VOC: 9.0%; 2 VOCs: 14.2%; 3 VOCs: 18.4%; ≥4 VOCs: 23.9%). At the time of survey, 83.2% of patients with 1 VOC, 92.6% with 2 VOCs, 94.0% with 3 VOCs, and 95.9% with ≥4 VOCs in the prior year experienced symptoms including chronic pain (1 VOC: 48.8%; 2 VOCs: 55.3%; 3 VOCs: 60.9%; ≥4 VOCs: 67.6%), acute pain (1 VOC: 33.7%; 2 VOCs: 45.3%; 3 VOCs: 54.5%; ≥4 VOCs: 65.3%), and fatigue (1 VOC: 35.8%; 2 VOCs: 43.2%; 3 VOCs: 42.9%; ≥4 VOCs: 54.7%). On an eleven-point scale where 0 is no pain and 10 is the worst possible pain, physicians reported that 21.2% of patients experienced the worst possible pain during their most recent VOC (1 VOC: 16.8%; 2 VOCs: 18.5%; 3 VOCs: 24.0%; ≥4 VOCs: 29.8%). Overall, 81.1% of patients were aware of what triggered their most recent VOC. The three most frequently reported triggers were dehydration, weather, and illness/infection. Of those patients who required care in a medical setting during their most recent VOC, 75.2% were treated with opioid medications. The three most frequently reported reasons for why the patient was not treated with opioids were that the pain was easily managed with other pain relief, the level of pain didn't warrant opioid use, and the physician had concerns for the patient's side effects. Of the patients who had been prescribed treatment for at least one year (n=771), 93.9% were treated with a SCD modifying treatment, including hydroxyurea, L-glutamine, and crizanlizumab (1 VOC: 91.9%; 2 VOCs: 93.2%; 3 VOCs: 94.7%; ≥4 VOCs: 97.6%). Overall, 49.4% of patients were completely adherent to their modifying treatment (1 VOC: 57.2%; 2 VOCs: 49.5%; 3 VOCs: 54.2%; ≥4 VOCs: 34.8%). Analgesic medications were prescribed to 87.8% of patients (1 VOC: 82.6%; 2 VOCs: 88.0%; 3 VOCs: 93.8%; ≥4 VOCs: 91.6%) including opioids in 33.3% (1 VOC: 23.3%; 2 VOCs: 34.2%; 3 VOCs: 38.9%; ≥4 VOCs: 44.0%). In the 12 months prior to the survey, 53.1% of patients had received at least one blood transfusion (1 VOC: 46.8%; 2 VOCs: 50.4%; 3 VOCs: 58.6%; ≥4 VOCs: 62.4%). Physicians reported high unemployment, high levels of both acute and chronic pain, and high levels of fatigue, especially among patients who had ≥4 VOCs in the 12 months prior to survey. Despite receiving modifying treatments and blood transfusions, patients still experienced high clinical morbidity and unemployment burden due to their SCD, with patients suffering the highest numbers of VOCs reporting the greatest impact. Novel SCD modifying treatments which reduce the frequency of VOCs may minimize the burden of disease and improve quality of life for patients.