Safety and efficacy of mitapivat in sickle cell disease (RISE UP): results from the phase 2 portion of a global, double-blind, randomised, placebo-controlled trial.

Background: Sickle cell disease, a debilitating, inherited haemolytic anaemia with premature morbidity and mortality, affects millions globally. Mitapivat, a first-in-class, oral, allosteric activator of pyruvate kinase, improves red blood cell survival by increasing ATP and diminishes sickling by decreasing 2,3-diphosphoglycerate. We aimed to evaluate the efficacy and safety of mitapivat in patients with sickle cell disease.

Expert consensus on the management of infusion-related reactions (IRRs) in patients with sickle cell disease (SCD) receiving crizanlizumab: a RAND/UCLA modified Delphi panel.

Crizanlizumab, a monoclonal antibody against P-selectin, has been shown to reduce vaso-occlusive crises (VOCs) compared to placebo in patients ≥ 16 years with sickle cell disease (SCD). However, there have been rare reports of patients experiencing severe pain and subsequent complications within 24 hours of crizanlizumab infusions. These events are defined as infusion-related reactions (IRRs).

Riociguat in patients with sickle cell disease and hypertension or proteinuria (STERIO-SCD): a randomised, double-blind, placebo controlled, phase 1-2 trial.

Background: Although nitric oxide based therapeutics have been shown in preclinical models to reduce vaso-occlusive events and improve cardiovascular function, a clinical trial of a phosphodiesterase 5 inhibitor increased rates of admission to hospital for pain. We aimed to examine if riociguat, a direct stimulator of the nitric oxide receptor soluble guanylate cyclase, causes similar increases in vaso-occlusive events.

Methods: This was a phase 1-2, randomised, double blind, placebo-controlled trial.

Opioid Prescribing and Outcomes in Patients With Sickle Cell Disease Post-2016 CDC Guideline.

Importance: Although the intention of the 2016 US Centers for Disease Control and Prevention (CDC) Guideline for Prescribing Opioids for Chronic Pain was not to limit pain treatment for patients with sickle cell disease (SCD), clinicians and patients have recognized the possibility that the guideline may have altered outcomes for this population. However, the outcomes of the 2016 guideline for this patient population are unknown.

Objective: To examine changes in opioid prescribing patterns and health outcomes among patients with SCD before and after the release of the 2016 CDC guideline.

Managing sickle cell disease and related complications in pregnancy: results of an international Delphi panel.

Data to guide evidence-based management of pregnant people with sickle cell disease (SCD) are limited. This international Delphi panel aimed to identify consensus among multidisciplinary experts for SCD management during pregnancy. The 2-round Delphi process used questionnaires exploring 7 topics (antenatal care, hydroxyurea use, transfusion, prevention of complications, treatment of complications, delivery and follow-up, and bottlenecks and knowledge gaps) developed by a steering committee.

Using disease-modifying therapies in sickle cell disease.

As curative therapy using allogeneic hematopoietic stem cell transplantation as well as gene therapy and gene editing remains inaccessible to most patients with sickle cell disease, the availability of drug therapies that are safe, efficacious, and affordable is highly desirable. Increasing progress is being made in developing drug therapies based on our understanding of disease pathophysiology. Four drugs, hydroxyurea, L-glutamine, crizanlizumab, and voxelotor, are currently approved by the US Food and Drug Administration, with multiple others at various stages of testing.

Hydroxyurea at escalated dose versus fixed low-dose hydroxyurea in adults with sickle cell disease.

Hydroxyurea reduces the frequency of vaso-occlusive complications, increases hemoglobin, and decreases mortality in sickle cell disease (SCD). Although current guidelines recommend escalation to maximum tolerated dose (MTD), the use of fixed low-dose hydroxyurea is common in low-resource countries. We conducted a systematic review and meta-analysis to evaluate the efficacy of escalated doses versus fixed low-dose of hydroxyurea in adults with SCD.

Comparative pharmacovigilance assessment of adverse events associated with the use of hydroxyurea, L-glutamine, voxelotor, and crizanlizumab in sickle cell disease.

Using disproportionality analysis, this study compared the adverse events (AEs) associated with the use of the new agents (e.g., L-glutamine, voxelotor, and crizanlizumab) to the commonly used medication, hydroxyurea, in sickle cell disease.

The challenge of clinical end points in sickle cell disease.

As most patients with sickle cell disease (SCD) do not have access to curative therapies, the availability of drug therapies that can modify disease severity remains highly desirable. Despite an increased understanding of the pathophysiology of SCD, only 4 drugs are approved by the US Food and Drugs Administration. Most drug trials in SCD have involved the use of acute pain episodes as the primary clinical end point.

Evaluation of treatment patterns, healthcare resource utilization and cost of illness for sickle cell disease in Ghana: a private medical insurance claims database study.

Background: Sickle cell disease (SCD) is a major public health concern in sub-Saharan Africa, accounting for nearly 75% of the global disease burden. The current analysis evaluated patient characteristics, treatment patterns, healthcare resource utilization (HCRU) and associated costs in patients with SCD based on a Private Medical Insurance Database in Ghana.

Methods: This retrospective longitudinal cohort study was conducted using an e-claims database from Ghana (01 January 2015 to 31 March 2021).

Kidney failure outcomes in children and young adults with sickle cell disease in the United States Renal Data System.

Background: Children and young adults with sickle cell disease (SCD) develop kidney disease early in childhood, with some patients progressing to require dialysis and kidney transplantation. The prevalence and outcomes of children with kidney failure (chronic kidney disease stage 5) due to SCD are not well described. This study aimed to assess the outcome of children and young adults with SCD with kidney failure compared to matched children and young adults without SCD with kidney failure in a large national database.

Age-related differences in risks and outcomes of 30-day readmission in adults with sickle cell disease.

Background: Literature on 30-day readmission in adults with sickle cell disease (SCD) is limited. This study examined the overall and age-stratified rates, risk factors, and healthcare resource utilization associated with 30-day readmission in this population.

Methods: Using the Nationwide Readmissions Database, a retrospective cohort study was conducted to identify adult patients (aged ≥ 18) with SCD in 2016.

End Stage Kidney Disease Outcomes in Children and Young Adults with Sickle Cell Disease in the United States Renal Data System.

Children and young adults with sickle cell disease (SCD) develop kidney disease early in childhood with some patients progressing to require dialysis and kidney transplantation. The prevalence and outcomes of children with end stage kidney disease (ESKD) due to SCD is not well described. This study aimed to assess the burden and outcomes of ESKD in children and young adults with SCD in a large national database.

Urinary angiotensinogen is associated with albuminuria in adults with sickle cell anaemia.

We explored the association of novel urinary biomarkers with albumin-creatinine ratio (ACR) in adults with sickle cell anaemia. Of 37 participants, 13 (35.2%) had persistent albuminuria (PA).

The Evolving Landscape of Drug Therapies for Sickle Cell Disease.

Although sickle cell disease can be cured using allogeneic hematopoietic stem cell transplantation and possibly gene therapy and gene editing, these treatments remain unavailable to most patients. As understanding of the disease pathophysiology increases, progress is being made in developing drug therapies. Hydroxyurea, l-glutamine, crizanlizumab, and voxelotor are currently approved by the US Food and Drug Administration, with multiple others at various stages of testing.

Longitudinal study of glomerular hyperfiltration in adults with sickle cell anemia: a multicenter pooled analysis.

Glomerular hyperfiltration is common in young sickle cell anemia patients and precedes development of overt kidney disease. In this multicenter pooled cohort, we characterized hyperfiltration and its decline to normal range in adult patients. Glomerular filtration rate (GFR) was estimated using the creatinine-based 2009 CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equation omitting race adjustment and the 2021 CKD-EPI equation.

The nephropathy of sickle cell trait and sickle cell disease.

Sickle cell syndromes, including sickle cell disease (SCD) and sickle cell trait, are associated with multiple kidney abnormalities. Young patients with SCD have elevated effective renal plasma flow and glomerular filtration rates, which decrease to normal ranges in young adulthood and subnormal levels with advancing age. The pathophysiology of SCD-related nephropathy is multifactorial - oxidative stress, hyperfiltration and glomerular hypertension are all contributing factors.

Enuresis and Hyperfiltration in Children With Sickle Cell Disease.

Nocturnal enuresis is a common symptom in children with sickle cell disease (SCD). Risk factors for development of enuresis are currently unknown. An early manifestation of SCD-associated kidney damage is glomerular hyperfiltration.