Introduction Anti-TNFα therapy has been associated with demyelination since early trials in Multiple Sclerosis (MS) demonstrated disease worsening.Subsequent small case series have reported plausible clinical associations although epidemiological studies have produced conflicting data.The specific clinical features of demyelination following anti-TNF therapy have not been described.This study uses a systematic independent assessment of causality to describe the clinical characteristics and outcomes of anti-TNFα associated demyelination.

Method Patients were recruited from 28 hospitals.Inclusion criteria included i)no history of neurological symptoms prior to anti-TNFα exposure,ii)MRI brain and/or spinal cord or electrophysiological tests consistent with PNS or CNS demyelination,iii)demyelination illness confirmed by neurologist and drug withdrawn.An adjudication panel comprising at least 3 neurologists and a neuro-radiologist identified definite and probable cases from case report forms.Probable cases required a consistent history and signs and objective radiological±electrophysiological evidence of demyelination.Definite cases had a recurrence of demyelination on drug rechallenge.

Results 54 cases were recruited, of whom 35 (24 female) were adjudicated as definite or probable cases. Adalimumab,Infliximab,Etanercept and Certolizumab were implicated in 17/35 (49%), 15/35 (43%), 5/35 (14%), and 1/35 (3%) of cases respectively.Average age of symptom onset was 40 (95%CI 37–44) years. The mean duration of anti-TNFα exposure was 27 (95%CI 18–36) months prior to symptom onset onset of demyelination. 22 cases (63%) presented with brain ± spinal lesions, 8 (23%) spine only demyelination, and 5 (14%) peripheral demyelination.On drug withdrawal patients were followed for a mean of 42 (95%CI 32–52) months.Of those with CNS lesions, 11/30 (37%) developed a relapsing demyelinating syndrome or MS and only 5/30 (17%) had complete resolution of their symptoms with a mean time to resolution of 419 days (95% CI 36–802).

Conclusion This large case series adds comprehensive clinical information to the existing reports of demyelinating events associated with anti-TNFα therapy for inflammatory disorders.Consistent with known risk factors for MS, young females appear to be over represented.Over one third of patients appear to develop a relapsing illness/MS and complete neurological recovery is uncommon.We aim to build this cohort further so that we might explore clinically useful genetic markers that identify at-risk patients.

Disclosure of Interest None Declared