P550 Clinical features of demyelination following anti-TNFα therapy

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Background: Anti-TNFα therapy has been associated with demyelination since early trials in Multiple Sclerosis (MS) demonstrated disease exacerbation. 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.

Methods: Patients were recruited from 27 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tests consistent with PNS or CNS demyelination, iii) demyelination illness confirmed by neurologist and drug withdrawn.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 re-challenge.

Results: 52 cases were recruited, of whom 34 (23 female) were adjudicated as definite or probable cases. Adalimumab, Infliximab, Etanercept and Certolizumab were implicated in 16/34 (47%), 12/34 (35%), 5/34 (15%), and 1/34 (3%) of cases respectively. Average age at symptom onset was 40 (95% CI 36–44) yrs. The mean duration of anti-TNFα exposure was 29 (95% CI 20–39) months prior to onset of demyelination. 19 (56%) cases presented with brain ± spinal lesions, 9 (26%) spine only demyelination, and 5 (15%) peripheral demyelination. 1 patient (3%) presented with both central and peripheral demyelination. On drug withdrawal patients were followed for a mean of 40 (95% CI 32–48) months. 11 (32%) of patients developed a relapsing demyelinating syndrome or MS and only 6 (18%) had complete resolution of their symptoms with a mean time to resolution of 381 days (95% CI 80–682).

Conclusions: This case series reports the clinical features of demyelinating events associated with anti-TNFα therapy. Consistent with known risk factors for MS, young females appear to be over represented. Approximately one third of patients appear to develop a relapsing illness/MS and complete neurological recovery is uncommon. We aim to build this cohort further to explore clinically useful genetic markers that identify at-risk patients.

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