Estudio de los posibles factores clínicos genéticos y ambientales asociados con la respuesta al tratamiento con acetato de glatirámero en pacientes con esclerosis múltiple

La esclerosis múltiple (EM) es una enfermedad desmielinizante y neurodegenerativa de la mielina y el axón del sistema nervioso central, que afecta a un elevado número de pacientes en los países occidentales siendo la segunda causa de discapacidad en los adultos jóvenes de estas poblaciones. Sus causas no se conocen de forma completa en la actualidad, pero se acepta que la enfermedad tiene un origen multifactorial, en el que participan por un lado factores ambientales y factores genéticos de susceptibilidad, y por otro una respuesta autoinmune inflamatoria contra esta mielina del sistema nervioso central y mecanismos degenerativos. La combinación de estos mecanismos fisiopatológicos genera 4 tipos clínicos de EM: la forma recurrente-remitente (EM-RR), secundariamente-progresiva (EM-SP), primariamente-progresiva (EM-PP), y primaria-recurrente (EM-PR). Actualmente existen varios tratamientos que han demostrado eficacia controlando el componente inflamatorio de la enfermedad, y por lo tanto disminuyendo la probabilidad de aparición de nuevos brotes. En concreto, en este momento en Europa, están aprobados varios tratamientos para las formas clínicas de EM-RR (IFN beta 1b (Betaferon ®, Extavia ®), IFN beta 1 a (Avonex ®, Rebif ®), acetato de glatirámero (Copaxone ®), mitoxantrona (Novantrone ®), natalizumab (Tysabri ®), fingolimod (Gilenya ®), teriflunomida (Aubagio ®), BG-12 (Tecfidera ®) y alemtuzumab (Lemtrada ®), y para los tipos de EM-SP (Betaferon ® , Extavia ®, Rebif ® y Novantrone ®)..

Teriflunomide and Epstein–Barr virus in a Spanish multiple sclerosis cohort: in vivo antiviral activity and clinical response

BackgroundEpstein–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.Objective1. 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.MethodsA 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).ResultsAntiviral 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.ConclusionTreatment 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