Natalizumab PML Risk — RACP Adult Medicine MCQ

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ModerateNeurologyNatalizumab PML RiskRACP Adult Medicine

A 42-year-old woman with multiple sclerosis on natalizumab for 3 years has a JCV antibody index of 2.5 (high). She has had 40 monthly infusions. What is the recommended action?

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Correct answer: A — Switch to an alternative DMT due to high PML risk

Natalizumab (anti-α4 integrin – highly effective for RRMS) carries a risk of PML (progressive multifocal leukoencephalopathy) that increases with: (1) JCV antibody positivity, (2) high JCV antibody index (>1.5), (3) treatment duration >24 months, and (4) prior immunosuppression. This patient has all three major risk factors – her estimated PML risk is >10 per 1000 patients. Switching to an alternative high-efficacy DMT (ocrelizumab, ofatumumab, or cladribine) is recommended. Extended-interval dosing (every 6–8 weeks) reduces PML risk while maintaining efficacy and may be considered as an alternative.

Reference: eTG – 2025 – Neurology; MS Research Australia – 2023 – MS Clinical Guidelines