Crizanlizumab for the Prevention of Vaso-Occlusive Pain Crises in Sickle Cell Disease

Stevens, Debra L; Hix, Meri; Gildon, Brooke L.

doi:10.1177/87551225211008460

Cited by 11 publications

(6 citation statements)

References 19 publications

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“…Crizanlizumab: This monoclonal antibody targets P-selectin, a molecule involved in the adhesion of sickled red blood cells. Clinical trials have explored its potential in preventing vaso-occlusive crises (Stevens et al, 2021).…”

Section: Anti-sickling Agentsmentioning

confidence: 99%

Emerging therapies and management approaches in sickle cell disease (SCD): A critical review

Patel,

Mukkala

et al. 2023

J. Phytonanotech. Pharmaceut. Sci.

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This comprehensive review delves into the intricate landscape of sickle cell disease (SCD), a global genetic disorder impacting individuals, healthcare systems, and communities. The article traces the historical origins of SCD, providing an in-depth exploration of its complex pathophysiology and the myriad clinical complications it engenders. Traditional management approaches, including pain management, blood transfusions, and hydroxyurea therapy, are scrutinized alongside assessing their associated limitations and challenges. Innovative therapies on the horizon, such as gene therapy, CRISPR/Cas9-based gene editing, and strategies to induce fetal hemoglobin production, offer glimmers of hope for potential curative interventions. Patient perspectives are seamlessly integrated, offering invaluable insights into the daily challenges and lived experiences of individuals grappling with SCD. The review underscores the pivotal role of multidisciplinary care teams, preventive strategies, patient education, and psychosocial support in optimizing SCD care. Furthermore, it examines the influence of healthcare policies, research funding, and advocacy organizations in propelling advancements in SCD management. Peering into the future, the article discusses the prospects of curative breakthroughs, precision medicine, enhanced pain management, and improved quality of life for SCD patients. It underscores the imperative of sustained research, collaborative efforts, and advocacy initiatives to tackle disparities, ensure equitable access to care, and foster innovation in SCD management.This comprehensive review provides a panoramic view of SCD, accentuating its complexities and the potential for transformative change in the lives of those affected. It issues a resounding call to action, championing continuous endeavors to enhance SCD care and pave the way for a brighter, healthier future for all impacted individuals.

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Section: Anti-sickling Agentsmentioning

confidence: 99%

Emerging therapies and management approaches in sickle cell disease (SCD): A critical review

Patel,

Mukkala

et al. 2023

J. Phytonanotech. Pharmaceut. Sci.

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“…In a recent therapeutic development, Crizanlizumab, a humanized monoclonal antibody to P-selectin, was clinically approved as a treatment for limiting thromboinflammation in sickle cell disease associated vaso-occlusive crisis. 96 Inhibitors that block the interaction of platelet GPIbα with MAC-1 can also reduce thrombosis. 92 Other platelet-associated receptor-ligand interactions such as programmed cell death protein 1 (PD)-1-PD ligand-1 (PDL-1) can also exert immunomodulatory functions in thromboinflammation.…”

Section: The Binding Between Platelet P-selectin With P-selectin Glyc...mentioning

confidence: 99%

“…Due to its key role in initiating platelet‐leukocyte interactions, P‐selectin has emerged as a therapeutic target to reduce thrombosis in many thrombo‐inflammatory diseases including DVT 95 and sickle cell disease. In a recent therapeutic development, Crizanlizumab, a humanized monoclonal antibody to P‐selectin, was clinically approved as a treatment for limiting thromboinflammation in sickle cell disease associated vaso‐occlusive crisis 96 . Inhibitors that block the interaction of platelet GPIbα with MAC‐1 can also reduce thrombosis 92 .…”

Section: Nanomedicine Inspired By Platelet Role In Thrombosis and Thr...mentioning

confidence: 99%

Platelet‐inspired nanomedicine in hemostasis thrombosis and thromboinflammation

Raghunathan

Rayes

Gupta

2022

Journal of Thrombosis and Haemostasis

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Platelets are anucleate cell‐fragments derived predominantly from megakaryocytes in the bone marrow and released in the blood circulation, with a normal count of 150 000–40 000 per μl and a lifespan of approximately 10 days in humans. A primary role of platelets is to aid in vascular injury site‐specific clot formation to stanch bleeding, termed hemostasis. Platelets render hemostasis by a complex concert of mechanisms involving platelet adhesion, activation and aggregation, coagulation amplification, and clot retraction. Additionally, platelet secretome can influence coagulation kinetics and clot morphology. Therefore, platelet defects and dysfunctions result in bleeding complications. Current treatment for such complications involve prophylactic or emergency transfusion of platelets. However, platelet transfusion logistics constantly suffer from limited donor availability, challenges in portability and storage, high bacterial contamination risks, and very short shelf life (~5 days). To address these issues, an exciting area of research is focusing on the development of microparticle‐ and nanoparticle‐based platelet surrogate technologies that can mimic various hemostatic mechanisms of platelets. On the other hand, aberrant occurrence of the platelet mechanisms lead to the pathological manifestation of thrombosis and thromboinflammation. The treatments for this are focused on inhibiting the mechanisms or resolving the formed clots. Here, platelet‐inspired technologies can provide unique platforms for disease‐targeted drug delivery to achieve high therapeutic efficacy while avoiding systemic side‐effects. This review will provide brief mechanistic insight into the role of platelets in hemostasis, thrombosis and thromboinflammation, and present the current state‐of‐art in the design of platelet‐inspired nanomedicine for applications in these areas.

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“…Crizanlizumab has raised great hope as it reduced VOC incidence by 45% in a phase II, double‐blind, placebo‐controlled and randomized clinical trial 6 . However, concerns exist about infusion‐related potentially severe reactions, 7 high cost 8 and uncertain long‐term efficacy of humanized monoclonal antibodies 9 . We have recently reported an increase in plasma histamine levels, possibly reflecting mast cell activation, in patients with SCD, particularly ≤18 years of age, at baseline and even more during VOCs 10 .…”

Section: Introductionmentioning

confidence: 99%

Oral famotidine reduces the plasma level of soluble P‐selectin in children with sickle cell disease

Allali,

Marquant,

Rignault‐Bricard

et al. 2023

Br J Haematol

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SummaryPlasma histamine levels are increased in patients with sickle cell disease (SCD), potentially promoting endothelial P‐selectin expression and vaso‐occlusion via histamine type 2 (H2) receptors. We conducted a prospective, non‐comparative, single‐centre study to determine whether famotidine, a H2 receptor antagonist, reduces P‐selectin expression in SCD children. The median plasma P‐selectin level was significantly reduced after 29 days of oral famotidine (53.2 ng/mL [IQR: 46.7–63.4] vs. 69.9 ng/mL [IQR: 53.6–84.2], median difference −10.2 ng/mL [IQR: −21.8 to −2.7], p = 0.005) in 28 patients. No effect was observed on other adhesion molecules, inflammation or haemolysis markers, except decreased reticulocyte count. No adverse events deemed related to famotidine were observed. Randomized controlled trials are now needed to assess the efficacy of famotidine in preventing vaso‐occlusion in SCD.

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Crizanlizumab for the Prevention of Vaso-Occlusive Pain Crises in Sickle Cell Disease

Cited by 11 publications

References 19 publications

Emerging therapies and management approaches in sickle cell disease (SCD): A critical review

Emerging therapies and management approaches in sickle cell disease (SCD): A critical review

Platelet‐inspired nanomedicine in hemostasis thrombosis and thromboinflammation

Oral famotidine reduces the plasma level of soluble P‐selectin in children with sickle cell disease

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