This meta-analysis examined CNS demyelination cases associated with TNF-α inhibitors, detailing clinical features, onset timing, management, and outcomes.

A comprehensive search across major databases from January 2005 to July 2025 identified reports of TNF-α inhibitors associated CNS demyelination. Two reviewers independently screened and extracted data on patient demographics, underlying diseases, type of TNF-α used, duration, and outcomes. A meta-analysis was performed to summarize the frequency of demyelinating events, mean age and time to onset.

A total of 79 studies published between 2005 to 2025 were included, encompassing 155 patients with TNF-α inhibitor associated CNS demyelination (63.9% females, 36.1% males). The most frequent events were relapsing-remitting multiple sclerosis (24.5%), optic neuritis (23.2%), and clinically isolated syndrome (16.1%). Adalimumab (34.2%), etanercept (30.3%), and infliximab (28.4%) were predominant agents implicated with shortest onset after certolizumab (8.74 months) and longest after etanercept (22.5 months). The mean age at onset ranged from 37.1 to 50 years across drugs. Most patients ceased TNF-α therapy and received corticosteroids; few required plasma exchange or IVIG. Disease modifying therapy such as rituximab and dimethyl fumarate were used in some cases. Overall, 56.1% achieved full recovery, 27.7% partial improvement, and 11% had no recovery. Observational data indicated an estimated 30% increased risk of demyelination with TNF-α inhibitors, though results remain inconsistent.

TNF-α inhibitors, though highly effective for autoimmune diseases, carry a rare but unpredictable risk of CNS demyelination. Most events were linked to adalimumab, etanercept, and infliximab. Although improved after discontinuation and steroid therapy. However, incomplete recovery in some patients highlights the need for cautious use, baseline neurological evaluation, and close monitoring for early demyelinating symptoms.