Teriflunomide and Epstein-Barr virus in a Spanish multiple sclerosis cohort:

Background

Epstein-Barr virus (EBV) and human herpesvirus 6 (HHV-6) have been associated with multiple sclerosis (MS). Teriflunomide is an oral disease-modifying therapy approved for treatment of relapsing forms of MS. In the preclinical Theiler's murine encephalitis virus model of MS, the drug demonstrated an increased rate of viral clearance versus the vehicle placebo. Furthermore, teriflunomide inhibits lytic EBV infection

Objective

1. To evaluate the humoral response against EBV and HHV-6 prior to teriflunomide treatment and 6 months later. 2. To correlate the variation in the humoral response against EBV and HHV-6 with the clinical and radiological response after 24 months of treatment with teriflunomide. 3. To analyze the utility of different demographic, clinical, radiological, and environmental data to identify early biomarkers of response to teriflunomide.

Methods

A total of 101 MS patients (62 women; mean age: 43.4 years) with one serum prior to teriflunomide onset and another serum sample 6 months later were recruited. A total of 80 had been treated for at least 24 months, 13 had stopped teriflunomide before 24 months, and 8 were currently under teriflunomide therapy but with less than 24 months of follow-up. We analyzed the levels of the viral antibodies titers abovementioned in serum samples with ELISA commercial kits, and the levels of serum neurofilament light chain (Nf-L).

Results

Antiviral antibody titers decreased for EBNA-1 IgG (74.3%), VCA IgG (69%), HHV-6 IgG (60.4%), and HHV-6 IgM (73.3%) after 6 months of teriflunomide. VCA IgG titers at baseline correlated with Nf-L levels measured at the same time (r = 0.221; p = 0.028) and 6 months later (r = 0.240; p = 0.017). We found that higher EBNA-1 titers (p = 0.001) and a higher age (p = 0.04) at baseline were associated with NEDA-3 conditions. Thus, 77.8% of patients with EBNA-1 >23.0 AU and >42.8 years (P50 values) were NEDA-3.

Conclusion

Treatment with teriflunomide was associated with a reduction of the levels of IgG antibody titers against EBV and HHV-6. Furthermore, higher EBNA-1 IgG titers prior to teriflunomide initiation were associated with a better clinical response.

Informations de copyright

Copyright © 2023 Domínguez-Mozo, González-Suárez, Villar, Costa-Frossard, Villarrubia, Aladro, Pilo, Montalbán, Comabella, Casanova-Peño, Martínez-Ginés, García-Domínguez, García-Martínez, Arroyo and Álvarez-Lafuente.

Déclaration de conflit d'intérêts

IG-S: reports compensation for consulting services and speaker honoraria from Biogen, Janssen, Merck-Serono, Novartis, Sanofi, and Roche. LV: has served at scientific advisory boards, participated in meetings sponsored by and received speaking honoraria or travel funding or research grants from Roche, Sanofi, Merck, Biogen, Bristol Myers, and Novartis. LC-F: reports compensation for consulting services and speaker honoraria from Biogen, Bristol Myers Squibb, Janssen, Merck-Serono, Novartis, Sanofi, Roche, and Teva. BP: has received speaker honoraria by Novartis and Almirall, travel honoraria by Merck, and training honoraria by Sanofi and Merck. XM: speaking honoraria and travel expenses for scientific meetings, has been a steering committee member of clinical trials or participated in advisory boards of clinical trials in the past 3 years with Actelion, Alexion, Biogen, Celgene, EMD Serono, Genzyme, Immunic, MedDay, Merck, Mylan, Novartis, Roche, Sanofi-Genzyme, and Teva Pharmaceutical. MC: compensation for consulting services and speaking honoraria from Bayer Schering Pharma, Merk Serono, Biogen-Idec, Teva Pharmaceuticals, Sanofi-Aventis, Genzyme, Bristol-Myers Squibb, and Novartis. IC-P: having received payments as speaker, and support for attending meetings from Bayern, Biogen, Merck, Novartis, Roche Sanofi, and Teva. MM-G: has received compensation for consulting services and speaking fees from Merck, Biogen, Novartis, Sanofi-Genzyme, Almirall, ROCHE, BMS, and TEVA. JG-D: honoraria as speaker, advisor or researcher from Almirall, Bristol-Myers-Squibb, Biogen, Janssen, Merck, Novartis, Roche, Teva, and Sanofi. RA: has been a speaker or has participated in the advisory board of Novartis, Teva, Roche, Bristol, Janssen, Biogen, Merck, and Sanofi-Genzyme. RA-L: has received support for attending meetings from Biogen, Novartis, and Sanofi-Genzyme. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.