Objective To estimate the effects of biological drugs on the risk of demyelinating events in rheumatoid arthritis (RA).

Methods Case–control analyses nested in an administrative database cohort.

Results Initially the risk of demyelinating events appeared to be increased after exposure to anakinra and decreased after exposure to antitumour necrosis factor (anti-TNF) agents. However, this apparent differential risk was due to more anakinra use (and avoidance of anti-TNF agents) in persons at high risk for demyelinating events. In individuals not at high risk, the adjusted rate ratio was 1.31 (95% CI 0.68 to 2.50) after exposure to anti-TNF agents and 0.80 (95% CI 0.29 to 2.24) after exposure to anakinra.

Conclusions When accounting for differential prescription patterns, there was a trend towards more events after exposure to anti-TNF agents. When studying rare but important potential drug associations, pharmacoepidemiological studies are valuable but must be carefully performed.