A 25-year-old woman with relapsing-remitting MS (RRMS) has had 2 relapses in the past year and new MRI lesions on low-efficacy therapy. Anti-JCV antibody index is 0.4. Which high-efficacy disease-modifying therapy (DMT) has the HIGHEST risk of progressive multifocal leucoencephalopathy (PML) and should be used cautiously?
- A Natalizumab ✓
- B Ocrelizumab
- C Alemtuzumab
- D Cladribine
Correct answer: A. Natalizumab
Explanation
Natalizumab (anti-VLA-4 integrin monoclonal antibody) carries the highest PML risk among MS DMTs because it prevents JC virus-specific cytotoxic T-cell trafficking into the CNS. Risk is stratified by anti-JCV antibody index: index >1.5 with prior immunosuppression and >2 years of natalizumab use confers highest risk (>1:100). At index 0.4, current risk is low but should be monitored every 6 months. Ocrelizumab (anti-CD20) carries very low PML risk. Alemtuzumab's main concerns are secondary autoimmunity. Cladribine's PML risk is theoretical/rare.
Reference: Harrison's Principles of Internal Medicine, 21st ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.