A 45-year-old woman with relapsing-remitting multiple sclerosis has been on interferon-beta for 2 years with two clinical relapses and new MRI lesions. She asks about escalation of therapy. Which of the following high-efficacy disease-modifying therapies carries risk of PML (progressive multifocal leukoencephalopathy) due to JC virus reactivation?
- A Natalizumab ✓
- B Ocrelizumab
- C Cladribine
- D Dimethyl fumarate
Correct answer: A. Natalizumab
Explanation
Natalizumab (anti-VLA-4 integrin monoclonal antibody) prevents lymphocyte trafficking into the CNS but blocks immune surveillance, leading to JC virus reactivation and PML — a potentially fatal or severely disabling opportunistic infection. Risk is stratified by anti-JCV antibody index; high-index seropositive patients on natalizumab for > 24 months have significantly elevated PML risk. Ocrelizumab, cladribine, and dimethyl fumarate have PML risk orders of magnitude lower.
Reference: Harrison's Principles of Internal Medicine, 21st ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.