Teriflunomide and Epstein–Barr virus in a Spanish multiple sclerosis cohort: in vivo antiviral activity and clinical response
Biomarker; Multiple sclerosis; Teriflunomide
| Authors: | ; ; ; ; ; ; ; |
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| Format: | Article |
| Status: | Published version |
| Publication date: | 2023 |
| Country: | España |
| Institution: | Departament de Salut de la Generalitat de Catalunya (DS) |
| Repository: | Scientia. Dipòsit d'Informació Digital del Departament de Salut |
| OAI Identifier: | oai:scientiasalut.gencat.cat:11351/10559 |
| Online Access: | https://hdl.handle.net/11351/10559 |
| Access Level: | Open access |
| Keyword: | Medicaments antivírics - Ús terapèutic Esclerosi múltiple Infeccions per virus d'Epstein-Barr DISEASES::Nervous System Diseases::Autoimmune Diseases of the Nervous System::Demyelinating Autoimmune Diseases, CNS::Multiple Sclerosis CHEMICALS AND DRUGS::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Anti-Infective Agents::Antiviral Agents DISEASES::Virus Diseases::DNA Virus Infections::Herpesviridae Infections::Epstein-Barr Virus Infections ENFERMEDADES::enfermedades del sistema nervioso::enfermedades autoinmunitarias del sistema nervioso::enfermedades autoinmunes desmielinizantes del SNC::esclerosis múltiple COMPUESTOS QUÍMICOS Y DROGAS::acciones y usos químicos::acciones farmacológicas::usos terapéuticos::antiinfecciosos::antivíricos ENFERMEDADES::virosis::infecciones por virus ADN::infecciones por Herpesviridae::infecciones por virus de Epstein-Barr |
| _version_ | 1878741351039762432 |
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| author | Dominguez-Mozo, Maria Inmaculada |
| author2 | González-Suárez, Inés Villar, Luisa M Costa-Frossard França, Lucienne Aladro, Yolanda Comabella Lopez, Manuel Villarrubia, Noelia Montalban, Xavier |
| author2_role | author author author author author author author |
| author_browse | Aladro, Yolanda Comabella Lopez, Manuel Costa-Frossard França, Lucienne Dominguez-Mozo, Maria Inmaculada González-Suárez, Inés Montalban, Xavier Villar, Luisa M Villarrubia, Noelia |
| author_facet | Dominguez-Mozo, Maria Inmaculada González-Suárez, Inés Villar, Luisa M Costa-Frossard França, Lucienne Aladro, Yolanda Comabella Lopez, Manuel Villarrubia, Noelia Montalban, Xavier |
| author_role | author |
| collection | Scientia. Dipòsit d'Informació Digital del Departament de Salut |
| description | Biomarker; Multiple sclerosis; Teriflunomide |
| eu_rights_str_mv | openAccess |
| format | article |
| id | ES_e3a7cce4eded12e132747c19f3c30f4f |
| institution | Departament de Salut de la Generalitat de Catalunya (DS) |
| instname_str | Departament de Salut de la Generalitat de Catalunya (DS) |
| network_acronym_str | ES |
| network_name_str | España |
| oai_identifier_str | oai:scientiasalut.gencat.cat:11351/10559 |
| publishDate | 2023 |
| publishDateSort | 2023 |
| publisher | Frontiers Media |
| publisherStr | Frontiers Media |
| reponame_str | Scientia. Dipòsit d'Informació Digital del Departament de Salut |
| spelling | Teriflunomide and Epstein–Barr virus in a Spanish multiple sclerosis cohort: in vivo antiviral activity and clinical response Dominguez-Mozo, Maria Inmaculada González-Suárez, Inés Villar, Luisa M Costa-Frossard França, Lucienne Aladro, Yolanda Comabella Lopez, Manuel Villarrubia, Noelia Montalban, Xavier Medicaments antivírics - Ús terapèutic Esclerosi múltiple Infeccions per virus d'Epstein-Barr DISEASES::Nervous System Diseases::Autoimmune Diseases of the Nervous System::Demyelinating Autoimmune Diseases, CNS::Multiple Sclerosis CHEMICALS AND DRUGS::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Anti-Infective Agents::Antiviral Agents DISEASES::Virus Diseases::DNA Virus Infections::Herpesviridae Infections::Epstein-Barr Virus Infections ENFERMEDADES::enfermedades del sistema nervioso::enfermedades autoinmunitarias del sistema nervioso::enfermedades autoinmunes desmielinizantes del SNC::esclerosis múltiple COMPUESTOS QUÍMICOS Y DROGAS::acciones y usos químicos::acciones farmacológicas::usos terapéuticos::antiinfecciosos::antivíricos ENFERMEDADES::virosis::infecciones por virus ADN::infecciones por Herpesviridae::infecciones por virus de Epstein-Barr Biomarker; Multiple sclerosis; Teriflunomide Biomarcador; Esclerosi múltiple; Teriflunomida Biomarcador; Esclerosis múltiple; Teriflunomida 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 in vitro. 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. AM has a technician contract from “REI: Red de Enfermedades Inflamatorias” (RD21/0002/0038). This work was financially supported by Ministerio de Ciencia e Innovación (Proyectos de generación de conocimiento)-Fondo Europeo de Desarrollo Regional (Feder) (PID2021-126041OB-I00) and “Fundación LAIR”. Frontiers Media https://hdl.handle.net/11351/10559 |
| spellingShingle | Teriflunomide and Epstein–Barr virus in a Spanish multiple sclerosis cohort: in vivo antiviral activity and clinical response Dominguez-Mozo, Maria Inmaculada Medicaments antivírics - Ús terapèutic Esclerosi múltiple Infeccions per virus d'Epstein-Barr DISEASES::Nervous System Diseases::Autoimmune Diseases of the Nervous System::Demyelinating Autoimmune Diseases, CNS::Multiple Sclerosis CHEMICALS AND DRUGS::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Anti-Infective Agents::Antiviral Agents DISEASES::Virus Diseases::DNA Virus Infections::Herpesviridae Infections::Epstein-Barr Virus Infections ENFERMEDADES::enfermedades del sistema nervioso::enfermedades autoinmunitarias del sistema nervioso::enfermedades autoinmunes desmielinizantes del SNC::esclerosis múltiple COMPUESTOS QUÍMICOS Y DROGAS::acciones y usos químicos::acciones farmacológicas::usos terapéuticos::antiinfecciosos::antivíricos ENFERMEDADES::virosis::infecciones por virus ADN::infecciones por Herpesviridae::infecciones por virus de Epstein-Barr |
| status_str | publishedVersion |
| title | Teriflunomide and Epstein–Barr virus in a Spanish multiple sclerosis cohort: in vivo antiviral activity and clinical response |
| title_full | Teriflunomide and Epstein–Barr virus in a Spanish multiple sclerosis cohort: in vivo antiviral activity and clinical response |
| title_fullStr | Teriflunomide and Epstein–Barr virus in a Spanish multiple sclerosis cohort: in vivo antiviral activity and clinical response |
| title_full_unstemmed | Teriflunomide and Epstein–Barr virus in a Spanish multiple sclerosis cohort: in vivo antiviral activity and clinical response |
| title_short | Teriflunomide and Epstein–Barr virus in a Spanish multiple sclerosis cohort: in vivo antiviral activity and clinical response |
| title_sort | Teriflunomide and Epstein–Barr virus in a Spanish multiple sclerosis cohort: in vivo antiviral activity and clinical response |
| topic | Medicaments antivírics - Ús terapèutic Esclerosi múltiple Infeccions per virus d'Epstein-Barr DISEASES::Nervous System Diseases::Autoimmune Diseases of the Nervous System::Demyelinating Autoimmune Diseases, CNS::Multiple Sclerosis CHEMICALS AND DRUGS::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Anti-Infective Agents::Antiviral Agents DISEASES::Virus Diseases::DNA Virus Infections::Herpesviridae Infections::Epstein-Barr Virus Infections ENFERMEDADES::enfermedades del sistema nervioso::enfermedades autoinmunitarias del sistema nervioso::enfermedades autoinmunes desmielinizantes del SNC::esclerosis múltiple COMPUESTOS QUÍMICOS Y DROGAS::acciones y usos químicos::acciones farmacológicas::usos terapéuticos::antiinfecciosos::antivíricos ENFERMEDADES::virosis::infecciones por virus ADN::infecciones por Herpesviridae::infecciones por virus de Epstein-Barr |
| topic_facet | Medicaments antivírics - Ús terapèutic Esclerosi múltiple Infeccions per virus d'Epstein-Barr DISEASES::Nervous System Diseases::Autoimmune Diseases of the Nervous System::Demyelinating Autoimmune Diseases, CNS::Multiple Sclerosis CHEMICALS AND DRUGS::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Anti-Infective Agents::Antiviral Agents DISEASES::Virus Diseases::DNA Virus Infections::Herpesviridae Infections::Epstein-Barr Virus Infections ENFERMEDADES::enfermedades del sistema nervioso::enfermedades autoinmunitarias del sistema nervioso::enfermedades autoinmunes desmielinizantes del SNC::esclerosis múltiple COMPUESTOS QUÍMICOS Y DROGAS::acciones y usos químicos::acciones farmacológicas::usos terapéuticos::antiinfecciosos::antivíricos ENFERMEDADES::virosis::infecciones por virus ADN::infecciones por Herpesviridae::infecciones por virus de Epstein-Barr |
| url | https://hdl.handle.net/11351/10559 |