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CNS demyelination with TNFα inhibitor exposure: A retrospective cohort study
Spencer K Hutto1, Dylan R Rice1, Farrah J Mateen1
1Department of Neurology, Massachusetts General Hospital, Boston, MA, USA.
Objective:
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.
Methods:
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.
Results:
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.
Conclusions:
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.
Insights
Patients exposed to tumor necrosis factor-alpha inhibitors (TNFai) can experience central nervous system (CNS) demyelinating events. Many patients show ongoing disease activity, including new MRI lesions and clinical relapses, even after discontinuing TNFai.
Area of Science:
- Neurology
- Immunology
- Neuroimmunology
Background:
- Tumor necrosis factor-alpha inhibitors (TNFai) are widely used for inflammatory conditions.
- The association between TNFai use and central nervous system (CNS) demyelinating events requires further investigation.
- Understanding long-term outcomes is crucial for managing patients with potential TNFai-induced demyelination.
Purpose of the Study:
- To evaluate the long-term clinical and radiological outcomes in patients experiencing CNS demyelinating events while on TNFai therapy.
- To assess the incidence of subsequent clinical relapse, new MRI lesions, and the need for disease-modifying therapy (DMT) for multiple sclerosis (MS).
- To analyze outcomes based on TNFai discontinuation and continuation/reinitiation.
Main Methods:
- Retrospective analysis of adult patients evaluated for CNS demyelinating disease during TNFai use between January 1998 and August 2020.
- Inclusion criteria: first neurological event during TNFai use, MRI lesions consistent with demyelination, and no alternative diagnosis.
- Patients were analyzed in clinically relevant subgroups, with data on clinical relapses, MRI findings, and DMT use.
Main Results:
- Twenty-one patients (mean age 44, 20 female) experienced index neurological events at a median of 12 months after starting TNFai.
- New MRI lesions developed in 67% of patients with follow-up MRIs, and 47% suffered clinical relapses.
- Despite discontinuing TNFai in 86% of cases, 56% showed further evidence of CNS demyelination, and 75% of those continuing/restarting TNFai relapsed.
Conclusions:
- A majority of patients with CNS demyelinating events during TNFai exposure exhibit a relapsing disease course.
- New MRI lesions and clinical relapses are common, even after TNFai discontinuation.
- These findings highlight the need for careful monitoring and management of CNS demyelination in patients using TNFai.
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