Demyelinating events following anti-tumor necrosis factor alpha therapy: Rare but challenging to treat

Demyelinating events are listed as adverse events with tumor necrosis factor alpha inhibitors (TNFi), but epidemiological studies have provided partly conflicting risk estimates. Furthermore, studies examining long-term outcomes of demyelinating events associated with TNFi are rare.

This was a retrospective, observational study comprising validation and tracking of long-term outcomes in patients referred to a tertiary neurology referral center for suspected neurological complications associated with TNFi.

Of 48 patients evaluated, only 14 showed signs of demyelinating disease on magnetic resonance imaging, where six fulfilled criteria for a clinically isolated syndrome (CIS) and eight were diagnosed with multiple sclerosis (MS). However, 13 patients had received an International Classification of Diseases code for MS at some stage. Mean follow-up from referral was 13 and 10.5 years among subjects with MS and CIS, respectively. Continued disease activity was recorded among several of those fulfilling MS criteria, and two ultimately underwent autologous hematopoietic stem cell transplantation. In contrast, subjects with CIS showed no progression after cessation of TNFi.

Our findings suggest that only a minority of those with suspected demyelinating disease following TNFi fulfill diagnostic criteria for MS and that MS diagnoses among those not fulfilling MS criteria may contribute to inflated epidemiological risk estimates. Nevertheless, in those fulfilling MS criteria, initiation of disease-modulating therapy, with escalation as needed, was important to suppress further disease activity.