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Case Reports
. 2020 Oct;267(10):2790-2796.
doi: 10.1007/s00415-020-09944-8. Epub 2020 Jun 3.

COVID-19 in teriflunomide-treated patients with multiple sclerosis

Amir Hadi Maghzi  1 , Maria K Houtchens  1 , Paolo Preziosa  2 , Carolina Ionete  3 , Biljana D Beretich  4 , James M Stankiewicz  1 , Shahamat Tauhid  1 , Ann Cabot  5 , Idanis Berriosmorales  3 , Tamara H W Schwartz  4 , Jacob A Sloane  6 , Mark S Freedman  7 , Massimo Filippi  2   8 , Howard L Weiner  1 , Rohit Bakshi  9
Affiliations
Case Reports

COVID-19 in teriflunomide-treated patients with multiple sclerosis

Amir Hadi Maghzi et al. J Neurol. 2020 Oct.

Abstract

The outbreak of a severe acute respiratory syndrome caused by a novel coronavirus (COVID-19), has raised health concerns for patients with multiple sclerosis (MS) who are commonly on long-term immunotherapies. Managing MS during the pandemic remains challenging with little published experience and no evidence-based guidelines. We present five teriflunomide-treated patients with MS who subsequently developed active COVID-19 infection. The patients continued teriflunomide therapy and had self-limiting infection, without relapse of their MS. These observations have implications for the management of MS in the setting of the COVID-19 pandemic.

Keywords: Antiviral; COVID-19; Coronavirus; Multiple sclerosis; Teriflunomide.

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Conflict of interest statement

MK Houtchens has received consulting fees from Biogen, EMD Serono, Sanofi-Genzyme, Mallinckrodt, Roche and research support from Biogen, EMD Serono, and Sanofi-Genzyme. P Preziosa has received speaking fees from Biogen, ExceMED, Merck Serono, and Novartis. C Ionete has received consulting fees from Sanofi-Genzyme, and research support from Biogen, EMD Serono, and Genentech. JM Stankiewicz has received consulting fees from Biogen, BMS/Celgene, EMD Serono, Genentech, Sanofi-Genzyme, and Novartis. A Cabot has received speaking fees from Alexion, Biogen, EMD/Serono, Genentech, Novartis, and Sanofi-Genzyme. JA Sloane has received consulting fees from Biogen, BMS/Celgene, EMD Serono, Genentech, Alexion, and Sanofi-Genzyme, and research support from National MS Society, Genentech, Biogen, EMD Serono, and Sanofi-Genzyme. MS Freedman has received research or educational grants from EMD Serono, Hoffman-La Roche, and Sanofi-Genzyme, and honoraria, consultation, or speaking fees from Actelion, Alexion, Atara, Bayer, Biogen, BMS/Celgene, Clene Nanomedicine, EMD Serono, GRI Bio, Hoffman La-Roche, Magenta Therapeutics, MedDay, Merck Serono, Novartis, Sanofi-Genzyme, and Teva. M Filippi has received consulting and/or speaking fees from Bayer, Biogen Idec, Merck-Serono, Novartis, Roche, Sanofi Genzyme, Takeda, and Teva, and research support from Biogen, Merck-Serono, Novartis, Roche, and Teva. HL Weiner has received consulting fees from Biodextris, Biogen, CBridge Capital, Everest Medicines, Genentech, Tiziana, Tilos, IM Therapeutics, Magnolia, MedDay, and vTv, and research support from Biogen, EMD Serono, Genentech, Sanofi-Genzyme, Google, Novartis; Teva, Tilos, and Verily. R Bakshi has received consulting fees from Bayer, Biogen, BMS/Celgene, EMD Serono, Genentech, and Novartis, and research support from BMS/Celgene, EMD Serono, and Sanofi-Genzyme. The other authors have nothing to disclose.

Figures

Fig. 1
Fig. 1
Patient 1: MRI findings. Representative MRI scans are shown from Patient 1. 3T imaging: in 2017, at the time of initial diagnosis of radiologically isolated syndrome (early multiple sclerosis—MS), fluid-attenuated inversion recovery (upper left, lower middle) showed multiple supratentorial hyperintense white matter lesions, and a pontine hyperintense lesion (arrow), consistent with MS. After gadolinium administration, the left posterior juxtacortical lesion showed enhancement (upper middle, arrow). Right column images show cervical spinal cord hyperintensity (arrows) consistent with MS. 7T imaging: a few years later, T2* imaging demonstrated central (hypointense) veins within a majority of T2 hyperintense lesions (lower left, arrow), highly consistent with MS
Fig. 2
Fig. 2
Patient 2: MRI findings. The most recent fluid-attenuated inversion-recovery scan is shown from Patient 2, obtained a few months before COVID-19 infection. Note multiple supratentorial hyperintense white matter lesions (right image), and a cerebellar white matter hyperintense lesion (arrow), consistent with multiple sclerosis
Fig. 3
Fig. 3
Teriflunomide: relevant potential dual mechanisms of actions. Teriflunomide may express a dual action relevant to active COVID-19 infection. Teriflunomide could potentially interfere with viral replication in infected cells by blocking de novo pyrimidine synthesis and exerting an antiviral effect (left image). In addition, within immune cells (right image), teriflunomide could dampen the unwanted host immune activation through three distinct mechanisms: 1. reducing cytokine production, in particular IL-6, which is thought to contribute to acute respiratory distress syndrome in COVID-19 infection; 2. decreasing immune cell activation by disrupting interactions with antigen-presenting cells (via non-DHOH-mediated impairment of integrin activation and decreased protein aggregation); and 3. blocking cell proliferation through depletion of the intracellular pyrimidine pool
See this image and copyright information in PMC

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