A 42-year-old man with relapsing-remitting multiple sclerosis (RRMS) on interferon beta-1a develops breakthrough disease: two relapses in 12 months and two new T2 lesions on MRI. He has no JC virus antibody. According to current EMA/FDA treatment escalation guidelines, the most appropriate high-efficacy DMT is:
- A Glatiramer acetate
- B Natalizumab ✓
- C Dimethyl fumarate
- D Teriflunomide
Explanation
In breakthrough RRMS with active disease on first-line therapy, escalation to high-efficacy DMT is recommended. Natalizumab (anti-VLA-4 antibody, blocks lymphocyte CNS entry) reduces relapses by ~68% and is preferred when JC virus antibody is negative because PML (progressive multifocal leukoencephalopathy) risk is lowest (JC-antibody negative = Stratify index negative). Glatiramer acetate, dimethyl fumarate, and teriflunomide are all moderate-efficacy agents not appropriate for breakthrough disease. JC-antibody positivity would favor switching to ofatumumab, ocrelizumab, or alemtuzumab.
Reference: Harrison's Principles of Internal Medicine, 21st ed.
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Written and medically reviewed by the StethoPrep medical team.