Real-World effectiveness of voxelotor for the treatment of sickle cell disease

Introduction: Voxelotor is a first-in- class sickle haemoglobin polymerisation inhibitor that targets the pathophysiology of sickle cell disease (SCD). Studies have shown that voxelotor increases haemoglobin and reduces markers of haemolysis. Emerging evidence suggests that voxelotor may improve the clinical symptoms of SCD, lower vaso-occlusive crisis (VOC) rates, and reduce transfusion needs. Objective(s): To examine the real-world impact of voxelotor on transfusion, VOC, and hospitalisation rates among patients with SCD. Method(s): Medical and pharmacy claims data for patients >=4 years with SCD who started voxelotor between November 2019 and March 2022 were obtained from the Symphony Health database. Patients with >=1 year of data before the index date (date of first voxelotor claim) were included. Annualised study outcomes were calculated for patients with >=1 occurrence of the corresponding event in the 3-month preindex period. Outcomes from a 90-day lookback were reported for the total and paediatric (aged 4 to <18 years) populations. Result(s): Of 4023 eligible patients from the Symphony Health database included in the analysis, 596 were <18 years. Compared with the 3-month preindex period, significantly lower annualised rates of transfusions, VOCs, and hospitalizations, and lower annualised mean number of inpatient days, were observed in the total population and paediatric subgroup over the 3-month postindex period. For the total population, the annualised event rates declined by 50.6% for transfusions (n = 248), 23.1% for VOCs (n = 1368), 35.5% for VOC-related hospitalizations (n = 757), and 39.4% for all-cause hospitalizations (n = 928). The annualised mean number of inpatient days declined by 29.6% for VOC-related hospitalizations (n = 757) and by 22.9% for all-cause hospitalizations (n = 928). For paediatric patients, the annualised event rates declined by 79.6% for transfusions (n = 18), 42.4% for VOCs (n = 157), 56.8% for VOC-related hospitalizations (n = 81), and 51.5% for all-cause hospitalizations (n = 106). The annualised mean number of inpatient days declined by 54.1% for VOC-related hospitalizations (n = 81) and by 45.8% for all-cause hospitalizations (n = 106). Conclusion(s): Treatment with voxelotor may provide a clinical benefit to patients with SCD by reducing the frequencies of transfusions, VOCs, and hospitalizations and decreasing inpatient days. Greater reductions were observed in the paediatric subgroup, potentially due to the smaller sample size, historically greater treatment compliance in paediatric patients, or younger patients having accumulated fewer SCD-related complications, enabling a greater clinical response. Limitations include the study's non-randomized design, reliance on claims data, and changes in healthcare use during the COVID-19 pandemic confounding the data.

MANAGEMENT OF SICKLE CELL DISEASE: A CLINICAL PRACTICE SURVEY

Background: Therapeutic options for Sickle Cell Disease (SCD) have increased recently as well as the development of updated national guidelines. It is not known how these options are being offered or to what degree guidelines are incorporated into clinical practice. Objectives: To assess the clinical practice patterns of providers treating children with SCD. Design/Method: A survey study was performed which included nine sections: clinic structure, prophylaxis, immunizations, hydroxyurea, splenic sequestration, stroke, novel therapies, potential curative therapies, and transition. Survey was disseminated over a three-month period via SurveyMonkey, to members of the American Society of Pediatric Hematology-Oncology Hemoglobinopathy Special Interest Group. Results: There were 86 respondents;most were attending/faculty (85%, 73/86) who were part of a university/academic practice (65%, 56/86). Program size was most commonly 50-250 patients (44%, 37/86). Accessibility to support staff in clinic included 95% (81/86) social work;76% (65/86) child life;68% (58/86) nurse coordinator and 34% (29/86) school liaison and 15% (13/86) transition navigator. For preventive care, 72% prescribe penicillin prophylaxis before 2 months of age recommending 100% (83) for HbSS and Sβnull, 72% (60/83) for HbSC and 70% (58/83) for HbSβplus. Influenza was the most common vaccine offered in clinic at 96% (76/79) with 91% (72/79) offering pneumococcal vaccines, 84% (67/79) offering meningococcal vaccines and 50% (40/79) offering COVID vaccines. Transcranial doppler screening was offered in 95% (69/73) but only 42% (31/73) performed MRI screening for silent stroke. Transfusion therapy was recommended for primary stroke prevention by 90% (65/72) and 84% (59/70) attempt to transition to hydroxyurea following TWITCH guidelines. For secondary stroke prevention, 88% (63/72) recommend chronic transfusion therapy. Regarding disease-modifying therapy, 90% (70/78) report starting hydroxyurea routinely in patients with HbSS and Sβnull;initiated at 9 months of age by 69% (54/78). Laboratory monitoring recommended every 3 months for stable dosing by 62% (49/78) and hydroxyurea held by 56% (44/78) if platelets <75,000, 73% (56/78) for neutrophils <1000. New therapies were recommended for patients on hydroxyurea who were still experiencing SCD complications: L-glutamine 68% (37/54;crizanlizumab 93% (54/58). Voxelotor was recommended for patients on hydroxyurea with low hemoglobin 65% (43/66). Matched sibling transplant was considered for any disease severity by 55% (38/69). Gene therapy trial is offered on-site by 29% (20/69). Transition programs were endorsed by 61% (42/69), but only 45% (31/68) had dedicated staff. Conclusion: This survey is the only assessment of the application of SCD guidelines in clinical practice.

Retrospective Study Evaluating Effect of Voxelotor Treatment on Acute Care Utilization during the Peak of COVID-19

Introduction In sickle cell disease (SCD), the polymerization of deoxygenated HbS fundamentally alters the structure of the erythrocyte, producing the sickle cell that is characteristic of the disease. Clinical manifestations often perceived in patients suffering from SCD include vaso-occlusion, anemia, and hemolysis. Due to these sequelae, patients frequent the emergency room (ER), urgent care clinic, and hospital. Voxelotor, an oral medication approved by the Food and Drug Administration (FDA) in 2019 for the treatment of SCD, directly targets the pathophysiology of SCD by inhibiting deoxygenated HbS polymerization. Results of the Phase III HOPE trial indicate that the drug can increase hemoglobin levels and reduce markers of hemolysis as well as the incidence of worsening anemia in patients with SCD (Vichinsky et al. N Engl J Med 2019). The COVID-19 pandemic has posed several challenges for patients with SCD in 2020. Amid the pandemic, patients continued to seek out acute medical care, including care in the ER, urgent care clinics, and hospital. The aim of this study was to determine whether utilization of acute medical care differed for patients who received voxelotor before and after therapy in 2020. We also evaluated the utilization of healthcare through telemedicine platforms to facilitate access to novel therapies such as voxelotor for patients with SCD. Methods 13 patients (≥18 years of age as of January 1, 2020) with SCD who had begun treatment with voxelotor between January 1, 2020 and December 31, 2020 were included in the initial analysis. Six patients were excluded from final analysis: three discontinued treatment due to side effects, one was noncompliant with treatment, and two were lost to follow-up. Acute care utilization, measured by the number of times each patient visited the ER, urgent care clinic, and hospital was compared for each patient in the period six months prior to their first dose of voxelotor and in the period six months after their last dose of the drug in 2020 using paired t-tests and Wilcoxon matched-pairs signed rank tests. Demographic information and the type of visit at which patients agreed to proceed with voxeletor was recorded for each patient. Simple linear regressions and multiple regressions controlled for covariates, defined as sex, BMI, age, type of insurance coverage, and duration of treatment. Results All seven (100%) patients discussed voxelotor treatment with their provider during a telehealth video visit. In the period before initiating treatment, patients frequented the ER an average of 2.71 (SD=6.75) times. In the six months after their last dose, patients visited the ER less than they had in the period prior to treatment, on average 0.57 (SD=0.79) times. This difference did not achieve statistical significance (p>0.9999). The mean number of visits to the urgent care clinic in the six months before treatment was 2.71 (SD=6.75) compared to 2 (SD=4) in the period after patients' last dose in 2020. This finding was not statistically significant (p>0.9999). Hospitalizations, on average, decreased significantly from 5.14 (SD=2.34) in the six months before starting treatment to 1.57 (SD=0.98) after ending therapy for 2020 (p=0.0015). Covariates did not have an effect on the differences in acute care utilization before treatment and after last treatment in 2020. Conclusions The findings of this study imply that treatment with voxelotor was associated with a decrease in the frequency of hospitalizations for the seven patients analyzed. This finding can potentially be attributed to the efficacy of voxelotor in improving anemia and reducing complications associated with SCD. While the difference between ER visits and urgent care visits before treatment and after the last dose in 2020 did not achieve statistical significance, likely due to small sample size, the data does suggest a reduction in both outcomes. In addition, the observation that all visits in which patient and provider discussed and initiated treatment were virtual support the use of telemedicine technology o improve access to multidisciplinary care and novel therapies for SCD patients. The impact of voxelotor treatment will continue to be assessed in SCD patients at our institution, and more data from clinical encounters will lead to a greater understanding of the efficacy of voxelotor. [Formula presented] Disclosures: Jain: GBT: Speakers Bureau;Novartis: Speakers Bureau;Sanofi: Other: advisory board;Argenx: Other: advisory board;DOVA: Other: advisory board.

Sickle Cell Disease and COVID-19 Infection: A Single-Center Experience

Background and Objectives: The COVID-19 (CO19) pandemic caused by SARS-CoV-2 remains a significant issue for global health, economics, and society. Several reports have shown that African Americans (AA) have been disproportionately affected by the CO19 pandemic. Limited data have suggested that sickle cell disease (SCD) could be one of the several reasons for higher morbidity and mortality related to CO19 among AA. Recent reports have suggested higher-than-average morbidity and mortality related to CO19 among patients with SCD. We conducted a retrospective, single-institution study in adult patients with SCD who were diagnosed with CO19 infection and their outcomes. Methods: After IRB approval, we conducted a chart review of adult patients (greater than 18 years) with SCD who were diagnosed with CO19 infection between March 1st, 2020, and March 31st, 2021. We recorded demographic data including age, gender, social factors (the type of insurance, availability of primary care provider (PCP), living alone/not), clinical parameters (type of SCD, co-morbidities), outpatient management of SCD, and how CO19 infection was managed like inpatient admission and complications. In patients who were admitted or seen in the emergency department (ED), we collected additional data including vitals, labs, the severity of illness, complications, length of stay, and outcomes. Computations were performed using statistical software SAS 9.4 for Windows. Results: We found a total of 51 patients with SCD diagnosed with CO19 infection in the above period. The median age of patients was 30 years. 61% were females and 39 % were males. All of them were AA. 11.76% were living alone, 49.02% were living with family, 1.96% (1 patient) was institutionalized, and the living situation was unknown in 37.25%. Most of the patients had Medicaid Insurance (52.94%), Medicare in 33.3%, private insurance in 13.73 % and 2% were uninsured. Only 64.71% of patients had a PCP. 60% had HbSS disease, 32% had HbSC disease, 4% had HbS-beta thalassemia, one patient each had HbSS with hereditary persistence of HbF and HbS/HbD. Comorbidities and previous history included acute chest syndrome in 65.96%, avascular necrosis in 36.96%, leg ulcers in 8.7%, hypertension in 8.7%, sickle cell retinopathy in 14.57%, cerebrovascular disease in 26.19%, chronic kidney disease in 7.69%, venous thromboembolism (VTE) in 20.41%, 10.41% were on anticoagulation, history of HIV and hepatitis C infection in 6.38%. 28.21% of patients were maintained on partial exchange transfusions as an outpatient for various indications. 72.73% were on hydroxyurea, 7.5% were on crizanlizumab, 5.26% were on voxelotor and 26.83% were on iron chelation. Vitals and pertinent lab values on initial assessment were recorded and many patients had missing data. On presentation, 25.53% were febrile, 29.17% of patients were tachycardic, 31.25% were hypoxic (SpO2 < 95%), 38.46% were tachypneic, 59.18% had a body mass index (BMI) of > 24.9. Median hemoglobin and hematocrit were 8.9/27.4 g/dL. The median white blood cell count was 9490/uL and platelets were 315,000/uL. Median ferritin was 1573 ug/L. Median bilirubin and creatinine were 2.05 mg/dL and 0.86 mg/dL. The patients were further stratified based on the clinical location where CO19 infection was managed (Table 1). 39.3% were diagnosed in the outpatient setting/ED and 60.3% in the inpatient setting. Among 51 patients, 5.71% (n=2) required ICU admission and was mechanically ventilated. 17.5% received dexamethasone, 7.69% received remdesivir, 2.76% received convalescent plasma, 17.07% had infections and 47% received antibiotics. Only one patient received an exchange transfusion during admission. One patient developed a new VTE after CO19 infection. On statistical analysis, the only factor which impacted the clinical location of management was tachycardia (P=0.007). Of the 51 patients, only 3.9% (2 patients) died of complications of CO19 infection, one with hypoxic respiratory failure, disseminated intravascular coagulation, shock, and the other one with pulmonary mbolism. 13% were readmitted within a month, one of them was admitted with a new pulmonary embolism and the others were admitted for acute painful episodes. Conclusion: We found a mortality rate of 3.9% in our single-center study of patients with SCD and CO19 infection. This mortality rate is lower than other published experiences in patients with SCD and CO19 infection. [Formula presented] Disclosures: Master: Blue Bird Bio: Current holder of individual stocks in a privately-held company.

Challenges in the Management of Sickle Cell Disease During SARS-CoV-2 Pandemic.

The management of sickle cell disease (SCD) and its complications in the COVID-19 era is very challenging. The recurrent sickling process in SCD causes tissue hypoxemia and micro-infarcts, resulting in end organ damage. Since the outbreak of SARS-CoV-2 pandemic, little data has been published about SCD concerning clinical presentation with COVID-19 and management. Hydroxyurea has been the cornerstone of management in children and adults with SCD, with evidence of its effect on controlling end organ damage. There are several anti-sickling drugs that have been approved recently that might have an additive value toward the management of SCD and its complications. The role of simple and exchange transfusions is well established and should always be considered in the management of various complications. The value of convalescent plasma has been demonstrated in small case series, but large randomized controlled studies are still awaited. Immunomodulatory agents may play a role in reducing the damaging effects of cytokines storm that contributes to the morbidity and mortality in advanced cases. Prophylactic anticoagulation should be considered in every management protocol because SCD and COVID-19 are thrombogenic conditions. Management proposals of different presentations of patients with SCD and COVID-19 are outlined.