A 28-year-old woman with sickle cell disease (HbSS) has frequent vaso-occlusive crises (4 in the past year) and a recent acute chest syndrome episode. She is not on hydroxyurea. A comprehensive disease-modifying strategy is being planned. The HOPE trial specifically evaluated which agent for adults with sickle cell disease experiencing ≥ 2 vaso-occlusive crises/year?
- A Crizanlizumab — evaluated in the HOPE trial for anti-P-selectin effect reducing vaso-occlusive crises
- B Voxelotor — evaluated in the HOPE trial showing reduction in sickling and improvement in haemoglobin levels ✓
- C L-glutamine — evaluated in the HOPE trial for decreasing oxidative stress in sickle cell disease
- D Luspatercept — evaluated in the HOPE trial for fetal haemoglobin induction
Explanation
The HOPE trial (NEJM 2019) evaluated voxelotor, a haemoglobin S polymerisation inhibitor (allosteric modifier of HbS) that maintains haemoglobin in the oxygenated R-state, preventing deoxygenation-induced sickling. HOPE showed voxelotor 1500 mg/day significantly increased haemoglobin ≥ 1 g/dL and reduced markers of haemolysis (indirect bilirubin, reticulocyte count) compared to placebo. Crizanlizumab (anti-P-selectin) was evaluated in the SUSTAIN trial for VOC reduction. L-glutamine was studied in a separate RCT published in 2018 for oxidative stress. Luspatercept targets ineffective erythropoiesis in thalassaemia.
Reference: Harrison's Principles of Internal Medicine, 21st ed.
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