CNS demyelination with TNFα inhibitor exposure: A retrospective cohort study

To study long-term outcomes in patients with CNS demyelinating events exposed to TNFa-inhibitors (TNFai), including subsequent clinical relapse, MRI lesions, and use of disease modifying therapy (DMT) for MS. Adult patients evaluated for a CNS demyelinating disease during TNFai use were identified a...

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Bibliographic Details
Published in:Journal of neuroimmunology 2021-07, Vol.356, p.577587-577587, Article 577587
Main Authors: Hutto, Spencer K., Rice, Dylan R., Mateen, Farrah J.
Format: Article
Language:English
Subjects:
CNS Inflammatory Disorder
Demyelination
Inflammation
Multiple sclerosis
TNF alpha inhibitor
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Summary:To study long-term outcomes in patients with CNS demyelinating events exposed to TNFa-inhibitors (TNFai), including subsequent clinical relapse, MRI lesions, and use of disease modifying therapy (DMT) for MS. Adult patients evaluated for a CNS demyelinating disease during TNFai use were identified at Mass General Brigham [01/1998–08/2020] and analyzed in clinically-relevant subgroups. Inclusion criteria required a first neurological event while taking a TNFai, MRI lesions consistent with demyelination, and the absence of a more probable alternative diagnosis. 21 cases (mean age 44 years, 20 female, 14 ≥ 2 MS risk factors) had an index neurological event (INE) at a median of 12 months (range 1–176) from onset of TNFai use (adalimumab in 10, etanercept 6, infliximab 5). MRI lesions were most often present in periventricular (16/20, 80%) and spinal zones (10/20, 50%); 37% (7/19) met ≥ 2 Barkhof criteria at onset. CSF testing was abnormal in 64% (7/11). 67% (10/15) with available follow-up MRIs developed new lesions by a median of 29.5 months of MRI surveillance (median MRI surveillance 60 months); 55% (11/20) met ≥ 2 Barkhof criteria. 47% (8/17) suffered a clinical relapse by a median of 40.5 months of clinic follow-up (median clinic follow-up since INE: 26 months). In patients discontinuing TNFai (18/21, 86%) at INE onset, 56% (10/18) had further evidence of CNS demyelination. Six patients (6/21, 29%) started an MS disease modifying therapy (DMT) at INE of whom 50% (3/6) had subsequent disease activity. Continuing or restarting TNFai was followed by relapse in 75% (3/4). 65% (13/20) met 2017 McDonald criteria for MS at INE with another 10% (15/20, 75%) by study conclusion. With extended follow-up, a majority of patients had a relapsing CNS demyelinating disorder—as evidenced by new MRI lesions or clinical relapses—despite TNFai discontinuation. [Display omitted] •TNF alpha inhibitors (TNFai) have been associated with central nervous system demyelination.•We retrospectively studied 21 cases of TNFai demyelination.•47% had a clinical relapse by a median of 41 months.•65% met 2017 McDonald criteria for multiple sclerosis at first neurological event.•With extended follow-up, most had a relapsing disorder despite discontinuing TNFai.
ISSN:0165-5728
1872-8421
DOI:10.1016/j.jneuroim.2021.577587