A 25-year-old woman with relapsing-remitting MS (3 relapses in 2 years, EDSS 3.5) is being counselled about high-efficacy disease-modifying therapy. Which mechanism characterizes natalizumab's mode of action?

• A Inhibits sphingosine-1-phosphate receptors trapping lymphocytes in lymph nodes
• B Monoclonal antibody against CD20 depleting B cells
• C Anti-α4-integrin antibody preventing lymphocyte trafficking across the blood-brain barrier ✓
• D Inhibits Bruton's tyrosine kinase in B cells

Explanation

Natalizumab is a humanized monoclonal antibody against α4-integrin (VLA-4) that prevents the binding of lymphocytes to VCAM-1 on CNS endothelium, thereby blocking lymphocyte trafficking across the blood-brain barrier into CNS tissue. Fingolimod inhibits S1P receptors causing lymphocyte sequestration. Ocrelizumab and rituximab target CD20 on B cells. Ibrutinib/evobrutinib inhibit BTK. Natalizumab's major risk is progressive multifocal leukoencephalopathy (PML) caused by JC virus reactivation, risk stratified by JCV antibody index.

Reference: Harrison's Principles of Internal Medicine, 21st ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.