A 28-year-old woman with sickle cell disease (HbSS) presents with a painful vaso-occlusive crisis. Her Hb is 7.8 g/dL (baseline 8.2). She is on hydroxyurea. Based on the HOPE trial (2019, NEJM), which newer agent approved for prevention of vaso-occlusive episodes in sickle cell disease targets P-selectin to reduce sickling-related inflammation?
- A Crizanlizumab (anti-P-selectin monoclonal antibody) ✓
- B Voxelotor (Hb S polymerization inhibitor)
- C L-glutamine (reduces oxidative stress in sickle RBCs)
- D Luspatercept (activin receptor ligand trap)
Explanation
Crizanlizumab (Adakveo) is a humanized monoclonal antibody against P-selectin, approved by FDA in 2019 based on the SUSTAIN trial. P-selectin on activated endothelium and platelets mediates adhesion of sickle RBCs, neutrophils, and platelets, initiating vaso-occlusion. By blocking P-selectin, crizanlizumab reduces vaso-occlusive crises frequency by ~45% compared to placebo. Voxelotor (HOPE trial) targets Hb S polymerization directly, increasing Hb S-oxygen affinity and reducing sickling — it improves Hb levels and reduces hemolysis markers but the primary endpoint was Hb rise, not VOC reduction. L-glutamine (Endari) reduces oxidative damage and was the first new SCD drug (2017 FDA) since hydroxyurea. Luspatercept is for beta-thalassemia.
Reference: Harrison's Principles of Internal Medicine, 21st ed.
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Written and medically reviewed by the StethoPrep medical team.