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PPMS Onset Upon Adalimumab Treatment Extends the Spectrum of anti-TNF-α Therapy-Associated Demyelinating Disorders

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PPMS Onset Upon Adalimumab Treatment Extends the Spectrum of anti-TNF-α Therapy-Associated Demyelinating Disorders

Sinah Engel et al. Ther Adv Neurol Disord.

Abstract

Since their introduction in 1999, anti-tumour necrosis factor-α (anti-TNF-α) therapies have been suspected repeatedly to be associated with the occurrence of central nervous system (CNS) demyelinating disorders, including multiple sclerosis (MS). However, recent publications were restricted to descriptions of monophasic demyelinating events or cases of relapsing-remitting MS (RRMS). We here provide the first case report of primary progressive MS (PPMS) onset upon anti-TNF-α therapy as well as a literature review of previously published cases of anti-TNF-α therapy-associated MS onset. The 51-year old male patient was treated with adalimumab due to psoriasis arthritis. About 18 months after treatment initiation, he developed slowly progressing neurological deficits including gait impairment, paraesthesia of the lower limbs, strangury and visual impairment, which led to the discontinuation of adalimumab therapy. Magnetic resonance imaging of the brain and the spinal cord revealed multiple inflammatory lesions and cerebrospinal fluid examination showed slight pleocytosis and positive oligoclonal bands. Thus, PPMS was diagnosed according to the 2017 revision of the McDonald criteria. As PPMS often causes only subtle symptoms in the beginning and early treatment discontinuation of anti-TNF-α therapy seems essential to improve the patient's outcome, we think that it is important to increase the awareness of slowly progressing neurological deficits as a potential adverse event of anti-TNF-α therapy among all clinicians involved in the initiation and monitoring of these drugs. In addition, the occurrence of both RRMS and progressive MS upon anti-TNF-α therapy might suggest a shared TNF-α-mediated pathophysiological mechanism in the evolution of all MS subtypes.

Keywords: adalimumab; anti-TNF-alpha therapy; primary progressive multiple sclerosis.

Conflict of interest statement

Conflict of interest statement: Sinah Engel, Aneka Mueller, Felix Luessi, Frauke Zipp and Stefan Bittner report no conflicts of interest associated with the publication of this manuscript. Rudolf E. Schopf has received honoraria/travel reimbursements from AbbVie, which were not associated with the submitted work.

Figures

Figure 1.
Figure 1.
Magnetic resonance imaging (MRI) and sequence analysis of the TNFRSF1A gene in the patient with primary progressive multiple sclerosis upon adalimumab treatment. T2-weighted sagittal MRI (A) and fluid attenuated inversion recovery (FLAIR) axial image (B) of the brain showed periventricular, corpus callosum and brainstem localized T2-hyperintense lesions (white arrows). No gadolinium enhancement was observed in T1Gd-weighted axial images (C). Proton density (PD)-weighted sagittal MRI of the spinal cord (D) revealed hyperintense cervical lesions (white arrows). The DNA sequence chromatogram (E) demonstrates a heterozygous A>G nucleotide change (red arrow) in intron 6 of TNFRSF1A gene (c.625+10A>G, rs1800693).

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