Background

The role of Epstein-Barr virus (EBV) in relapsing-remitting multiple sclerosis (MS) pathogenesis is poorly understood. Options for inhibiting EBV are limited except for possibly teriflunomide, which has been associated with inhibitory activity against EBV and other viruses (Mei-Jiao G, et al. Biomed Pharmacother 2019). Inhibition of EBV activity could contribute to teriflunomide’s efficacy in MS. The most direct method of quantitatively measuring EBV activity in vivo is to measure EBV shedding in saliva.

Objectives

To quantify EBV in the saliva of teriflunomide-treated MS patients, compared with 3 control cohorts of patients with MS.

Methods

Patients stable on teriflunomide for ≥3 months were prospectively recruited from 2 large MS practices in Australia. Saliva was collected at home each week for 3 months, per a standardized protocol. Saliva specimens were stored in patients’ home freezers for 6 weeks, then shipped to Queen Mary University of London for quantitative measurements of EBV DNA. EBV shedding was defined as >5.8 copies/µL. Results were compared with samples from 3 separate reference cohorts of MS patients not taking teriflunomide, which served as controls; all samples were analyzed using the same lab and assay.

Results

Over 3 months, EBV DNA was detected in 11/19 (58%) teriflunomide-treated patients; 5 (26%) had EBV shedding detected in ≥1 samples. In control cohorts, EBV DNA was detected in 61%−70% of patients, with EBV shedding present in ≥1 samples in 37%−45% of patients (P=not significant vs teriflunomide). However, when looking at 211 saliva samples from the teriflunomide-treated patients, 20% had detectable EBV DNA and 9.5% had EBV shedding. Samples from control cohorts had significantly higher proportions with detectable EBV DNA (38%−41%) and shedding (21%−24%) versus those from teriflunomide-treated patients (all P<0.0001). The number of samples positive for EBV detection and shedding in the teriflunomide-treated group was mainly driven by 2 patients with consistent shedding, whereas positive samples were spread evenly in the control cohorts.

Conclusions

Of 19 teriflunomide-treated patients, only 2 had consistent EBV shedding in saliva, suggesting teriflunomide may inhibit EBV shedding. Future studies could confirm this relationship by quantifying EBV shedding before and after teriflunomide initiation. Longer-term studies comparing the clinical courses of EBV shedders and nonshedders may help determine the role of EBV in MS.

STUDY SUPPORT: Sanofi.