Crizanlizumab in Sickle Cell Disease

Abstract

Vaso-occlusion in sickle cell disease (SCD) leads to a myriad of manifestations driving morbidity and mortality in patients with SCD. Increased leucocyte adhesion and P-selectin expression on platelets and endothelial cells is an inciting event that leads to obstruction of microcirculation by adhesion with rigid sickled red blood cells. Crizanlizumab is a first-in-class monoclonal antibody that inhibits P-selectin and has been shown to decrease the frequency of vaso-occlusive pain crises in patients with SCD in clinical trials. The role of crizanlizumab in other manifestations of SCD still needs further investigation.

Plain language summary

There are more than 100,000 people in the USA living with sickle cell anemia, which is a form of the inherited blood disorder, sickle cell disease. Patients with sickle cell anemia are typically diagnosed through newborn screening programs. They are also diagnosed during times of vaso-occlusive pain crisis, where patients present with severe pain without an obvious cause, and also through hemolytic anemia, a disorder in which red blood cells are destroyed faster than they can be made.

While children typically survive into adulthood, the life expectancy of those with sickle cell remains shorter secondary to the after-effects of chronic sickling, where the hemoglobin inside red blood cells sticks or clumps together, causing the cell to become fragile. The associated complications of chronic sickling include pulmonary hypertension (high blood pressure in the arteries of the lung and the right side of the heart), heart failure, stroke, liver dysfunction and splenic infarction, where the blood flow to the spleen is compromised. Crizanlizumab is a new therapy targeting p-selectin, a protein that blocks interaction with p-selectin glycoprotein ligand, and has shown promise in reducing vaso-occlusive crises.

Tweetable abstract

Crizanlizumab is a first-in-class monoclonal antibody that inhibits P-selectin and has been shown to decrease the frequency of vaso-occlusive pain crises in patients with sickle cell disease.

Keywords::

• crizanlizumab
• P-selectin
• pain crisis
• sickle cell disease
• vaso-occlusion

Author contributions

K Kaur and K Kennedy contributed equally to the preparation of this manuscript. D Liles directed the overall preparation of the manuscript and revisions. All three authors were involved in conducting the literature review, drafting the work and revising it critically for important intellectual content, and approved the final version to be submitted for publication.

Financial disclosure

The authors have no financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Competing interests disclosure

The authors have no competing interests or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Writing disclosure

No writing assistance was utilized in the production of this manuscript.