Sickle cell disease (SCD) is a genetic disorder, characterized by hemolytic anemia and vaso‐occlusive crises (VOCs). Data on the global SCD impact on quality of life (QoL) from the patient viewpoint are limited. The international Sickle Cell World Assessment Survey (SWAY) aimed to provide insights into patient‐reported impact of SCD on QoL. This cross‐sectional survey of SCD patients enrolled by healthcare professionals and advocacy groups assessed disease impact on daily life, education and work, symptoms, treatment goals, and disease management. Opinions were captured using a Likert scale of 1‐7 for some questions; 5‐7 indicated “high severity/impact.” Two thousand one hundred and forty five patients (mean age 24.7 years [standard deviation (SD) = 13.1], 39% ≤18 years, 52% female) were surveyed from 16 countries (six geographical regions). A substantial proportion of patients reported that SCD caused a high negative impact on emotions (60%) and school achievement (51%) and a reduction in work hours (53%). A mean of 5.3 VOCs (SD = 6.8) was reported over the 12 months prior to survey (median 3.0 [interquartile range 2.0‐6.0]); 24% were managed at home and 76% required healthcare services. Other than VOCs, fatigue was the most commonly reported symptom in the month before survey (65%), graded “high severity” by 67% of patients. Depression and anxiety were reported by 39% and 38% of patients, respectively. The most common patient treatment goal was improving QoL (55%). Findings from SWAY reaffirm that SCD confers a significant burden on patients, epitomized by the high impact on patientsʼ QoL and emotional wellbeing, and the high prevalence of self‐reported VOCs and other symptoms.

Nephropathy is a common and progressive complication of sickle cell anemia (SCA). In SCA mice, we found that hyperangiotensinemia in the absence of hypertension underlies nephropathy, and its downregulation by losartan, an angiotensin-II-receptor-1 blocker, reduced albuminuria and progression of nephropathy. Therefore, we performed a phase-2 trial of oral losartan, given for 6 months, to explore whether it reduced albuminuria in children and adults with SCA. Participants were allocated to groups defined by class of baseline urinary albumin-to-creatinine ratio (UACR): no albuminuria (NoA), microalbuminuria (MicroA), and macroalbuminuria (MacroA). The primary endpoint was a ≥25% reduction UACR from baseline. There were 32 evaluable participants (mean age 24 years; NoA=14, MicroA=12, MacroA=6). The primary endpoint was met in 83% of the MacroA group (P<0.0001) and 58% of the MicroA group (P<0.0001). Median fold-change in UACR was −0.74 for MacroA and −0.46 for MicroA. In MacroA and MicroA, UACR classification improved in 50% but worsened in 11%. Urine osmolality and estimated glomerular filtration rate (eGFR) did not change significantly. Losartan was discontinued in 3 participants [leg cramps, N=1; decline in eGFR >25% (142→104 mL/minute/1.73 m2), N=1; rise in serum creatinine >50% (0.2→0.3 mg/dL), N=1]. Albuminuria was associated with diastolic dysfunction and impaired functional capacity, although cardiopulmonary status was unchanged after 6 months of losartan therapy. In summary, losartan decreased urinary albumin excretion in most participants with albuminuria. Those with macroalbuminuria had the greatest benefit. This study forms the basis for a phase-3, randomized, placebo-controlled trial of losartan for the nephropathy of SCA.

Background: Sickle cell disease (SCD) is a multi-system disease affecting millions of people. The disease is characterized by vaso-occlusive crises (VOCs), resulting in acute and chronic pain, end-organ damage and life-threatening complications. The symptoms experienced by patients, caused largely by multi-cellular adhesion leading to vaso-occlusion and vasculopathy, significantly affect their quality of life (QoL) and ability to work/study. Understanding the effect of SCD on patients' daily lives can inform management of the disease and improve patients' QoL. Aims: To assess the impact of SCD on patients' daily lives, including physical symptoms, emotional wellbeing and economic burden, based on the worldwide SWAY survey. Methods: SWAY is an ongoing multi-country, cross-sectional survey of SCD patients, caregivers and treating physicians. Data are collected using self-completed or proxy surveys and categories include demographics, symptoms and impact of disease (physical, emotional and financial) and need for a caregiver. Where relevant, questions include a 7-point severity scale for each statement, with a score of 5 to 7 indicating 'high severity/impact'. Patient enrollment is via treating physicians and patient association groups. The enrollment target is approximately 2000 patients. Results: To date, 1513 SCD patients (48% male, mean age 24.1 years, 63% HbSS and 30% SC disease) have been surveyed from countries across the world, including the USA (365), UK (299), Nigeria (264), Ghana (255), Brazil (160) and Germany (91). The most commonly experienced symptoms of SCD were bone aches (63%), difficulty concentrating (49%), difficulty gaining weight (49%) and joint stiffness (41%). For these symptoms, 67%, 53%, 70% and 59% of patients rated them as 'high severity' on the 7-point scale, respectively. Background pain was present on an average of 2.9 days per week (standard deviation [SD]=2.2). Commonly experienced complications of SCD include fever (65%), joint issues (55%) and infections (55%). Patients reported a total of 7829 VOCs, with a mean of 5.2 VOCs per patient (SD=5.07) in the 12 months before survey completion; 38% of these VOCs resulted in overnight hospitalization, 24% were managed at home, 19% were treated in the emergency room and 19% of patients sought medical assistance in the community. A high impact on emotional wellbeing was reported by 61% of patients. The highest impact was caused by frustration with symptoms (60%), worry about disease worsening (59%) and worry about family/friends/children who care for them (54%). Only 42% of patients have received professional emotional support (eg psychiatrist, psychologist, counseling), but 67% reported a desire to receive this support. A high impact on household daily activities (eg food preparation, housework, childcare) and on family or social life was reported by 39% and 43% of patients, respectively, with 34% stating a high impact in terms of sexual desire/activity and 35% a high impact on relationships with spouse/partner. Physical activity was also affected in patients with SCD, with 60% reporting they avoid intense physical activity and 30% avoiding even mild physical activity, most commonly because of concerns about pain, exhaustion and dehydration (58%, 57% and 50%, respectively). Of the patients surveyed, 32% were employed, 8% not working but seeking employment, 6% not working and not seeking employment, 36% students, 1% retired, 13% on disability pay and 1% long-term sick leave. Employed patients reported SCD had a high impact on their ability to work, with 57% reducing their hours and 47% considering leaving their job. An average of 6.3 hours missed from work was reported in the 7 days prior to survey completion due to SCD. Half of patients believe that their income would be higher if they did not have SCD, 60% reported often missing school in the past and 52% felt that their disease has had a negative impact on their academic achievements. Conclusions: The acute and chronic symptoms associated with SCD have a substantial impact on patients' daily lives, including emotional and physical wellbeing, relationships and school/work. In addition, the acute symptoms associated with VOCs occur several times a year, resulting in frequent hospitalizations. Improved management of SCD would enhance patients' quality of life both at home and at school/work, likely leading to improved emotional wellbeing and a positive economic effect. Disclosures Osunkwo: Micella Biopharma: Other: DSMB Member ; Novartis: Consultancy, Speakers Bureau; Pfizer: Consultancy; Terumo: Speakers Bureau. Andemariam:Bluebird Bio: Membership on an entity's Board of Directors or advisory committees; Global Blood Therapeutics: Other: DSMB Member; Imara: Research Funding; NovoNordisk: Membership on an entity's Board of Directors or advisory committees; Sanofi Genzyme: Membership on an entity's Board of Directors or advisory committees; Terumo BCT: Membership on an entity's Board of Directors or advisory committees; Cyclerion: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Emmaus: Membership on an entity's Board of Directors or advisory committees; New Health Sciences: Membership on an entity's Board of Directors or advisory committees; Community Health Network of Connecticut: Consultancy. El-Rassi:Novartis Pharmaceuticals: Research Funding. Francis-Gibson:Sickle Cell Disease Association of America: Employment. Nero:Novartis: Consultancy. Minniti:Doris Duke Foundation: Research Funding. Trimnell:Global Blood Therapeutics: Consultancy; Novartis: Consultancy; Cyclerion: Consultancy. Abboud:AstraZeneca: Membership on an entity's Board of Directors or advisory committees, Research Funding; CRSPR Therapeutics: Membership on an entity's Board of Directors or advisory committees; Modus: Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Eli Lilly: Research Funding; GBT: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Other: Travel support; Novo Nordisk: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Colombatti:Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Addmedica: Membership on an entity's Board of Directors or advisory committees; Global Blood Therapeutics: Membership on an entity's Board of Directors or advisory committees. de Montalembert:AddMedica: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; bluebird bio, Inc: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Jastaniah:Novartis Pharmaceuticals: Consultancy, Honoraria. Nur:Novartis Pharmaceuticals: Consultancy. DeBonnett:Novartis Pharmaceuticals Corporation: Employment. James:Sickle Cell Society: Employment; Novartis: Honoraria.

Proper management of sickle cell anemia (SCA) begins with establishing the correct diagnosis early in life, ideally during the newborn period. The identification of affected infants by neonatal screening programs allows early initiation of prophylactic penicillin and pneumococcal immunizations, which help prevent overwhelming sepsis. Ongoing education of families promotes the early recognition of disease-released complications, which allows prompt and appropriate medical evaluation and therapeutic intervention. Periodic evaluation by trained specialists helps provide comprehensive care, including transcranial Doppler examinations to identify children at risk for primary stroke, plus assessments for other parenchymal organ damage as patients become teens and adults. Treatment approaches that previously highlighted acute vaso-occlusive events are now evolving to the concept of preventive therapy. Liberalized use of blood transfusions and early consideration of hydroxyurea treatment represent a new treatment paradigm for SCA management.

There is an immediate need to address long-standing questions about the reproductive health of girls and women with sickle cell disease (SCD). There are many SCD-related reproductive risks and uncertainties across girls' and women's reproductive life span, with particularly outstanding concerns about menstruation, contraception, fertility and pregnancy. Extant literature addressing women's reproductive health topics is mostly descriptive; there are few high-quality interventional studies. In 2020, the Centers for Disease Control and Prevention and the Foundation for Women and Girls with Blood Disorders convened an expert panel to assess the knowledge gaps in women's reproductive health in SCD. The panel identified significant limitations to clinical care due to the need for research. The panel also identified prominent barriers to research and care. In this report, we frame these issues, providing a roadmap for investigators, funding agencies, and policy makers to advance care for girls and women with SCD.

Barriers to completing age-appropriate recommended pneumococcal immunizations should be identified and addressed to further reduce invasive pneumococcal disease in this high-risk patient population.

Sickle cell disease (SCD) and β-thalassemia are among the most common inherited diseases, affecting millions of persons globally. It is estimated that 5-7% of the world's population is a carrier of a significant hemoglobin variant. Without early diagnosis followed by initiation of preventative and therapeutic care, both SCD and β-thalassemia result in significant morbidity and early mortality. Despite great strides in the understanding of the molecular basis and pathophysiology of these conditions, the burden of disease remains high, particularly in limited resource settings. Current therapy relies heavily upon the availability and safety of erythrocyte transfusions to treat acute and chronic complications of these conditions, but frequent transfusions results in significant iron overload, as well as challenges from acquired infections and alloimmunization. Hydroxyurea is a highly effective treatment for SCD but less so for β-thalassemia, and does not represent curative therapy. As technology and use of cellular and gene therapies expand, SCD and thalassemia should be among the highest disease priorities.

Background: Sickle cell disease (SCD) is an inherited systemic disorder in which sickle hemoglobin (HbS) polymerization triggers red blood cell sickling, chronic hemolytic anemia, and recurrent episodes of vaso-occlusion. SCD-related complications lead to acute and chronic life-threatening events, cumulative organ damage, disability, and early mortality. Voxelotor (Oxbryta ®) tablets are approved in the United States for treatment of SCD in adults and adolescents aged ≥12 years, based on the efficacy and safety data from the randomized, placebo-controlled, multicenter HOPE trial. Voxelotor is an oral, once-daily HbS-polymerization inhibitor that has been shown to increase hemoglobin (Hb) levels and reduce markers of hemolysis. The Retrospective Study to Evaluate Outcomes in Patients with Sickle Cell Disease Treated with Oxbryta (RETRO) is designed to collect, aggregate, and characterize real-world, retrospective laboratory and clinical data on adults and adolescents with SCD treated with voxelotor as part of their usual care at multiple clinical centers in the United States. Methods: RETRO is a multicenter, post-marketing, retrospective study of approximately 300 patients (aged ≥12 years) with SCD from 10 US study sites. Independent SCD expertise is provided by a steering committee to inform the design and conduct of the voxelotor registry. Clinical and laboratory data have been collected and aggregated 12 months before initiation of voxelotor treatment and compared with post-treatment data outcomes. Patients with documented SCD (all genotypes) who received voxelotor treatment for ≥2 consecutive weeks were included in this analysis. Only data available from patients' medical records (and other secondary data sources) 1 year before and up to 1 year after the first voxelotor dose were documented in de-identified case report forms via an electronic data capture system. Results: Forty-nine patients whose data were entered at 5 sites at the time of data cutoff (June 25, 2021) were included (mean age [SD]: 34.3 [12.91] years; 57.1% female; 85.7% HbSS and 6.1% HbSβ 0 genotype). Mean (SD) duration of voxelotor treatment was 48.1 (23.0) weeks. The initial prescribed voxelotor dose strengths (n, %) were 500 mg (4, 8.2%), 1000 mg (7, 14.3%), and 1500 mg (38, 77.6%). Rationale for prescription (n, %) included reduction of anemia (36, 73.5%), reduction in frequency of vaso-occlusive crises (23, 46.9%), reduction in pain (34, 69.4%), reduction in the need for blood transfusion (8, 16.3%) and other (5, 10.2%); more than 1 reason may have been selected. In 35 patients with recorded baseline and post-treatment Hb values, the peak observed post-treatment Hb (mean [SD]) was 9.4 (2.44) g/dL, an increase of 1.6 (1.5) g/dL from baseline (7.8 [2.02] g/dL). Fifty percent (11/22) of patients had a clinical response (Hb increase of &gt;1.0 g/dL from baseline) within 12 months of voxelotor treatment. Per-patient peak changes in Hb during the study period showed that 62.9% of patients experienced a response at some time up to 12 months during treatment (Figure). Change in hemolytic markers was also evaluated. In patients with recorded baseline and post-treatment reticulocyte percentage (N=19) and indirect bilirubin (N=24), the mean (SD) absolute post-treatment value was 7.4% (4.65%) for reticulocyte percentage, a decrease of 4.9% (6.63%) compared with baseline (12.4% [8.32%]), and 1.9 (1.66) mg/dL for indirect bilirubin, a decrease of 17.7 (81.83) mg/dL compared with baseline (19.6 [81.82] mg/dL). The most common non-SCD-related treatment-emergent adverse events (AEs) were diarrhea, headache, and rash (Table); 19 (38.8%) patients reported ≥1 AE, and most non-SCD-related AEs were mild in severity. Conclusions: RETRO is the first multicenter, retrospective study to examine the real-world effectiveness of voxelotor and describe the observed changes in laboratory and clinical outcomes after ≥2 weeks of therapy. This study shows that voxelotor treatment was associated with increased Hb levels and decreased hemolytic markers. The safety data are consistent with those from the HOPE trial. Further evaluation is needed, with additional data from all 10 sites, and will be presented later. Funding: This study was supported by Global Blood Therapeutics. Figure 1 Figure 1. Disclosures Achebe: Fulcrum Therapeutics: Consultancy; Pharmacosmos: Membership on an entity's Board of Directors or advisory committees; Global Blood Therapeutics: Membership on an entity's Board of Directors or advisory committees. Clay: GBT: Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria. Nero: Global Blood Therapeutics: Consultancy; Editas Medicine: Consultancy; bluebird bio: Consultancy; Novartis: Consultancy. Osunkwo: Terumo: Consultancy; Global Blood Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Acceleron: Consultancy; Forma Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees; Health and Services Administration: Research Funding; Patient Centered Outcomes Research Instituted: Research Funding; Micella Biopharma: Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Chiesi: Consultancy; Cyclerion: Consultancy; Emmaus: Consultancy. Idowu: Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; Global Blood Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Ironwood: Research Funding; Forma Therapeutics, Inc.: Research Funding; Pfizer: Research Funding. Shah: Novartis: Research Funding, Speakers Bureau; Alexion: Speakers Bureau; Emmaus: Consultancy; GBT: Consultancy, Research Funding, Speakers Bureau; Guidepoint Global: Consultancy; CSL Behring: Consultancy; GLG: Consultancy; Bluebird Bio: Consultancy. Curtis: GBT: Consultancy. Minniti: Bluebird Bio: Other: Endpoint adjudicator ; F. Hoffmann-La Roche Ltd: Consultancy; Chiesi: Consultancy; Novo Nordisk: Consultancy; Forma: Consultancy; Novartis: Consultancy; GBT: Consultancy; CSL Behring: Other: Endpoint adjudicator .