Paradigm shifts in multiple sclerosis management: Implications for daily clinical practice.

Multiple sclerosis (MS) is the most common chronic inflammatory neurological disease. The emergence of disease-modifying therapies (DMTs) has greatly improved disease activity control and progression of disability in MS patients. DMTs differ in their mode of action, route of administration, efficacy, and safety profiles, offering multiple options for clinicians. Personalized medicine aims at tailoring the therapeutic strategy to patients' characteristics and disease activity but also patients' needs and preferences. New therapeutic options have already changed treatment paradigms for patients with active relapsing MS (RMS). The traditional approach consists in initiating treatment with moderate-efficacy DMTs and subsequently, escalating to higher-efficacy DMTs when there is evidence of clinical and/or radiological breakthrough activity. Recent real-world studies suggest that initiation of high-efficacy DMTs from disease onset can improve long-term outcomes for RMS patients. In this article, we review different treatment strategies and discuss challenges associated with personalized therapy.

Structural and Biochemical Basis for Development of Diketo Acid Inhibitors Targeting the Cap-Snatching Endonuclease of the Ebinur Lake Virus (Order: Bunyavirales).

The Bunyavirales contain many important human pathogens that lack an antiviral therapy. The cap-snatching endonuclease (EN) of segmented negative-strand RNA viruses is an attractive target for broad-spectrum antivirals due to its essential role in initiating viral transcription. L-742,001, a previously reported diketo acid inhibitor against influenza virus EN, demonstrated potent EN inhibition and antiviral activity on various bunyaviruses. However, the precise inhibitory mechanism of the compound is still poorly understood. We recently characterized a highly active EN from Ebinur Lake virus (EBIV), a newly identified member of the Orthobunyavirus genus, and obtained its high-resolution structures, paving the way for structure-guided inhibitor development. Here, nine L-742,001 derivatives were designed and synthesized de novo, and their structure-activity relationship with EBIV EN was studied. In vitro biochemical data showed that the compounds inhibited the EBIV EN activity with different levels and could be divided into three categories. Five representative compounds were selected for further cell-based antiviral assay, and the results largely agreed with those of the EN assays. Furthermore, the precise binding modes of L-742,001 and its derivatives in EN were revealed by determining the high-resolution crystal structures of EN-inhibitor complexes, which suggested that the p-chlorobenzene is essential for the inhibitory activity and the flexible phenyl has the greatest exploration potential. This study provides an important basis for the structure-based design and optimization of inhibitors targeting EN of segmented negative-strand RNA viruses. IMPORTANCE The Bunyavirales contain many important human pathogens such as Crimean-Congo hemorrhagic fever virus and Lassa virus that pose serious threats to public health; however, currently there are no specific antiviral drugs against these viruses. The diketo acid inhibitor L-742,001 is a potential drug as it inactivates the cap-snatching endonuclease (EN) encoded by bunyaviruses. Here, we designed and synthesized nine L-742,001 derivatives and assessed the structure-activity relationship using EN of the newly identified Ebinur Lake virus (EBIV) as a research model. Our results revealed that the p-chlorobenzene of this broad-spectrum EN inhibitor is crucial for the inhibitory activity and the flexible phenyl "arm" has the best potential for further optimization. As cap-snatching ENs are present not only in bunyaviruses but also in influenza viruses, our data provide important guidelines for the development of novel and more potent diketo acid-based antiviral drugs against those viruses.

Therapeutic response to leflunomide in combo therapy and monotherapy is associated to serum teriflunomide (A77 1726) levels.

There is a significant rate of therapeutic failure in rheumatoid arthritis (RA) patients treated with leflunomide (LEF). This study investigates the utility values of teriflunomide levels (A77 1726) in identifying RA patients who remained with moderate or severe disease activity after the treatment with LEF. In this cross-sectional study, we compared: (a) RA patients who achieved a DAS28-ESR ≤ 3.2, and (b) RA patients who maintained a DAS28-ESR > 3.2 after treatment. ROC curves determined the cut-off of A77 1726 with the better performance to identify patients achieving a DAS28-ESR ≤ 3.2. Of the 115 patients treated with LEF, 69 (60%) remained with moderate/severe disease activity and 46 (40%) achieved low disease activity/remission. Higher A77 1726 levels showed a negative correlation with DAS28-ESR (r = - 0.42, p < 0.001) and other parameters of disease activity. We obtained the following utility values with the cut-off of A77 1726 > 10 µg/mL to identify RA patients who achieved a DAS28-ESR ≤ 3.2: sensitivity of 91.31%; specificity of 73.91%; positive predictive value of 70.00%; and negative predictive value of 92.73%. Serum A77 1726 discriminated between RA patients who remained with moderate/severe disease activity despite the treatment with LEF both as monotherapy and LEF as combo therapy.

Quantitative Proteomics Reveals the Role of Lysine 2-Hydroxyisobutyrylation Pathway Mediated by Tip60.

Lysine 2-hydroxyisobutyrylation (Khib) is a new type of posttranslational modifications (PTMs) extensively reported on eukaryotic cell histones. It is evolutionarily conserved and participates in diverse important biological processes, such as transcription and cell metabolism. Recently, it has been demonstrated that Khib can be regulated by p300 and Tip60. Although the specific Khib substrates mediated by p300 have been revealed, how Tip60 regulates diverse cellular processes through the Khib pathway and the different roles between Tip60 and p300 in regulating Khib remain largely unknown, which prevents us from understanding how this modification executes its biological functions. In this study, we report the first Khib proteome mediated by Tip60. In total, 3502 unique Khib sites from 1050 proteins were identified. Among them, 536 Khib sites from 406 proteins were present only in Tip60 overexpressing cells and 13 Khib sites increased more than 2-fold in response to Tip60 overexpression, indicating that Tip60 significantly affected global Khib. Notably, only 5 of the 549 Tip60-targeted Khib sites overlapped with the 149 known Khib sites targeted by p300, indicating the different Khib substrate preferences of Tip60 and p300. In addition, the Khib substrates regulated by Tip60 are deeply involved in processes such as nucleic acid metabolism and translation, and some are associated with Parkinson's and Prion diseases. In summary, our research reveals the Khib substrates targeted by Tip60, which elucidates the effect of Tip60 in regulating various cellular processes through the Khib pathway, and proposes novel views into the functional mechanism of Tip60.

Affimer Tagged Cubosomes: Targeting of Carcinoembryonic Antigen Expressing Colorectal Cancer Cells Using In Vitro and In Vivo Models.

Nanomedicines, while having been approved for cancer therapy, present many challenges such as low stability, rapid clearance, and nonspecificity leading to off-target toxicity. Cubosomes are porous lyotropic liquid crystalline nanoparticles that have shown great premise as drug delivery vehicles; however, their behavior in vivo is largely underexplored, hindering clinical translation. Here, we have engineered cubosomes based on the space group Im3m that are loaded with copper acetylacetonate as a model drug, and their surfaces are functionalized for the first time with Affimer proteins via copper-free click chemistry to actively target overexpressed carcinoembryonic antigens on LS174T colorectal cancer cells. Unlike nontargeted cubosomes, Affimer tagged cubosomes showed preferential accumulation in cancer cells compared to normal cells not only in vitro (2D monolayer cell culture and 3D spheroid models) but also in vivo in colorectal cancer mouse xenografts, while exhibiting low nonspecific absorption and toxicity in other vital organs. Cancerous spheroids had maximum cell death compared to noncancerous cells upon targeted delivery. Xenografts subjected to targeted drug-loaded cubosomes showed a 5-7-fold higher drug accumulation in the tumor tissue compared to the liver, kidneys, and other vital organs, a significant decrease in tumor growth, and an increased survival rate compared to the nontargeted group. This work encompasses the first thorough preclinical investigation of Affimer targeted cubosomes as a cancer therapeutic.

Multiple Sclerosis in Children: Differential Diagnosis, Prognosis, and Disease-Modifying Treatment.

Pediatric-onset multiple sclerosis (POMS) is a rare neuroinflammatory and neurodegenerative disease that has a significant impact on long-term physical and cognitive patient outcomes. A small percentage of multiple sclerosis (MS) diagnoses occur before the age of 18 years. Before treatment initiation, a careful differential diagnosis and exclusion of other similar acquired demyelinating syndromes such as anti-aquaporin-4-associated neuromyelitis optica spectrum disorder (AQP4-NMOSD) and myelin oligodendrocyte glycoprotein antibody spectrum disorder (MOGSD) is warranted. The recent 2017 changes to the McDonald criteria can successfully predict up to 71% of MS diagnoses and have good specificity of 95% and sensitivity of 71%. Additional measures such as the presence of T1-weighted hypointense lesions and/or contrast-enhancing lesions significantly increase the accuracy of diagnosis. In adults, early use of disease-modifying therapies (DMTs) is instrumental to a better long-term prognosis, including lower rates of relapse and disability worsening, and numerous FDA-approved therapies for adult-onset MS are available. However, unlike their adult counterparts, the development, testing, and regulatory approval of POMS treatments have been significantly slower and hindered by logistic and/or ethical considerations. Currently, only two MS DMTs (fingolimod and teriflunomide) have been tested in large phase III trials and approved by regulatory agencies for use in POMS. First-line therapies not approved by the FDA for use in children (interferon-ß and glatiramer acetate) are also commonly used and result in a significant reduction in inflammatory activity when compared with non-treated POMS patients. An increasing number of POMS patients are now treated with moderate efficacy therapies such as dimethyl fumarate and high-efficacy therapies such as natalizumab, anti-CD20 monoclonal antibodies, anti-CD52 monoclonal antibodies, and/or autologous hematopoietic stem cell transplantation. These high-efficacy DMTs generally provide additional reduction in inflammatory activity when compared with the first-line medications (up to 62% of relapse-rate reduction). Therefore, a number of phase II and III trials are currently investigating their efficacy and safety in POMS patients. In this review, we discuss potential changes in the regulatory approval process for POMS patients that are recommended for DMTs already approved for the adult MS population, including smaller sample size for pharmacokinetic/pharmacodynamic studies, MRI-centered primary outcomes, and/or inclusion of teenagers in the adult trials.

Hepatotoxicity associated with the use of teriflunomide in a patient with multiple sclerosis: A case report.

RATIONALE: Teriflunomide is an inhibitor of pyrimidine synthesis available as a first-line treatment for relapsing-remitting multiple sclerosis. Drug-induced liver damage is a relevant problem in clinical practice, representing a frequent cause of treatment discontinuation. This case report describes the occurrence of liver injury, with a 33.7-fold increase in the upper limit of normality of the liver enzyme alanine aminotransferase during treatment with teriflunomide 14 mg. PATIENT CONCERN: A 44-year-old woman receiving teriflunomide 14 mg for the treatment of multiple sclerosis presented symptoms suggestive of liver dysfunction 54 days after starting treatment. The patient had no history of using disease-modifying therapy, neither previous liver disease nor other comorbidities. DIAGNOSTICS: The suggested diagnosis was drug-induced liver injury, classified as hepatocellular. Other possible hepatic and autoimmune etiologies were ruled out. INTERVENTIONS: Replacement of teriflunomide treatment with glatiramer acetate and follow-up of the disease. OUTCOMES: Signs and symptoms regressed after treatment with teriflunomide 14 mg was discontinued, with normalization of liver enzyme activity in ∼5 months. The causality assessment of the adverse drug reaction was determined by the Naranjo scaling system, resulting in probable, with a final score of 7. CONCLUSIONS: Teriflunomide-induced liver injury in patients with multiple sclerosis is a serious adverse reaction. The report of this case contributes to updating knowledge about the safety aspects of treatment with teriflunomide and planning of monitoring strategies and patient risk management.

Teriflunomide Treatment of Multiple Sclerosis Selectively Modulates CD8 Memory T Cells.

Background and Objectives: Inhibition of de novo pyrimidine synthesis in proliferating T and B lymphocytes by teriflunomide, a pharmacological inhibitor of dihydroorotate dehydrogenase (DHODH), has been shown to be an effective therapy to treat patients with MS in placebo-controlled phase 3 trials. Nevertheless, the underlying mechanism contributing to the efficacy of DHODH inhibition has been only partially elucidated. Here, we aimed to determine the impact of teriflunomide on the immune compartment in a longitudinal high-dimensional follow-up of patients with relapse-remitting MS (RRMS) treated with teriflunomide. Methods: High-dimensional spectral flow cytometry was used to analyze the phenotype and the function of innate and adaptive immune system of patients with RRMS before and 12 months after teriflunomide treatment. In addition, we assessed the impact of teriflunomide on the migration of memory CD8 T cells in patients with RRMS, and we defined patient immune metabolic profiles. Results: We found that 12 months of treatment with teriflunomide in patients with RRMS does not affect the B cell or CD4 T cell compartments, including regulatory TREG follicular helper TFH cell and helper TH cell subsets. In contrast, we observed a specific impact of teriflunomide on the CD8 T cell compartment, which was characterized by decreased homeostatic proliferation and reduced production of TNFα and IFNγ. Furthermore, we showed that DHODH inhibition also had a negative impact on the migratory velocity of memory CD8 T cells in patients with RRMS. Finally, we showed that the susceptibility of memory CD8 T cells to DHODH inhibition was not related to impaired metabolism. Discussion: Overall, these findings demonstrate that the clinical efficacy of teriflunomide results partially in the specific susceptibility of memory CD8 T cells to DHODH inhibition in patients with RRMS and strengthens active roles for these T cells in the pathophysiological process of MS.

An updated review of teriflunomide's use in multiple sclerosis.

Teriflunomide, a once daily, oral disease-modifying therapy, has demonstrated consistent efficacy, safety and tolerability in patients with relapsing forms of multiple sclerosis (MS) and with a first clinical episode suggestive of MS treated up to 12 years. This review is an update to a previous version that examined data from the teriflunomide core clinical development program and extension studies. Data have since become available from active comparator trials with other disease-modifying therapies, treatment-related changes in brain volume (analyzed using structural image evaluation using normalization of atrophy) and real-world evidence including patient-reported outcomes. Initial data on the potential antiviral effects of teriflunomide in patients with MS, including case reports of patients infected with the 2019 novel coronavirus (SARS-CoV-2), are also presented.

Lay abstract Teriflunomide, a treatment taken orally once a day, has shown consistent effectiveness and safety in patients with relapsing forms of multiple sclerosis (MS). This review is an update to a previous version that summarized the trials from when teriflunomide was in clinical development for MS. Some of the newer studies described here compared teriflunomide with other MS treatments. Studies have shown positive effects of teriflunomide on brain volume; teriflunomide may also be effective against some viruses. People taking teriflunomide generally report stable cognition and quality of life, with no worsening of fatigue or disability. In the EU, teriflunomide has been recently approved for use in pediatric patients 10 years of age and above.

Potential risk of disease modifying therapies on neoplasm development and coadjutant factors in multiple sclerosis outpatients.

Neoplasm development in Multiple Sclerosis (MS) patients treated with disease-modifying therapies (DMTs) has been widely discussed. The aim of this work is to determine neoplasm frequency, relationship with the prescription pattern of DMTs, and influence of the patients' baseline characteristics. Data from 250 MS outpatients were collected during the period 1981-2019 from the medical records of the Neurology Service of the HUPM (Hospital Universitario Puerta del Mar)-in Southern Spain-and analysed using Cox models. Neoplasm prevalence was 24%, mainly located on the skin, with cancer prevalence as expected for MS (6.8%). Latency period from MS onset to neoplasm diagnosis was 10.4 ± 6.9 years (median 9.30 [0.9-30.5]). During the observation period ß-IFN (70.4% of patients), glatiramer acetate (30.4%), natalizumab (16.8%), fingolimod (24.8%), dimethyl fumarate (24.0%), alemtuzumab (6.0%), and teriflunomide (4.8%) were administered as monotherapy. Change of pattern in step therapy was significantly different in cancer patients vs unaffected individuals (p = 0.011) (29.4% did not receive DMTs [p = 0.000]). Extended Cox model: Smoking (HR = 3.938, CI 95% 1.392-11.140, p = 0.010), being female (HR = 2.006, 1.070-3.760, p = 0.030), and age at MS diagnosis (AGE-DG) (HR = 1.036, 1.012-1.061, p = 0.004) were risk factors for neoplasm development. Secondary progressive MS (SPMS) phenotype (HR = 0.179, 0.042-0.764, p = 0.020) and treatment-time with IFN (HR = 0.923, 0.873-0.977, p = 0.006) or DMF (HR = 0.725, 0.507-1.036, p = 0.077) were protective factors. Tobacco and IFN lost their negative/positive influence as survival time increased. Cox PH model: Tobacco/AGE-DG interaction was a risk factor for cancer (HR = 1.099, 1.001-1.208, p = 0.049), followed by FLM treatment-time (HR = 1.219, 0.979-1.517). In conclusion, smoking, female sex, and AGE-DG were risk factors, and SPMS and IFN treatment-time were protective factors for neoplasm development; smoking/AGE-DG interaction was the main cancer risk factor.

Efficacy and safety of dihydroorotate dehydrogenase (DHODH) inhibitors "leflunomide" and "teriflunomide" in Covid-19: A narrative review.

Dihydroorotate dehydrogenase (DHODH) is rate-limiting enzyme in biosynthesis of pyrimidone which catalyzes the oxidation of dihydro-orotate to orotate. Orotate is utilized in the biosynthesis of uridine-monophosphate. DHODH inhibitors have shown promise as antiviral agent against Cytomegalovirus, Ebola, Influenza, Epstein Barr and Picornavirus. Anti-SARS-CoV-2 action of DHODH inhibitors are also coming up. In this review, we have reviewed the safety and efficacy of approved DHODH inhibitors (leflunomide and teriflunomide) against COVID-19. In target-centered in silico studies, leflunomide showed favorable binding to active site of MPro and spike: ACE2 interface. In artificial-intelligence/machine-learning based studies, leflunomide was among the top 50 ligands targeting spike: ACE2 interaction. Leflunomide is also found to interact with differentially regulated pathways [identified by KEGG (Kyoto Encyclopedia of Genes and Genomes) and reactome pathway analysis of host transcriptome data] in cogena based drug-repurposing studies. Based on GSEA (gene set enrichment analysis), leflunomide was found to target pathways enriched in COVID-19. In vitro, both leflunomide (EC50 41.49 ± 8.8 µmol/L) and teriflunomide (EC50 26 µmol/L) showed SARS-CoV-2 inhibition. In clinical studies, leflunomide showed significant benefit in terms of decreasing the duration of viral shredding, duration of hospital stay and severity of infection. However, no advantage was seen while combining leflunomide and IFN alpha-2a among patients with prolonged post symptomatic viral shredding. Common adverse effects of leflunomide were hyperlipidemia, leucopenia, neutropenia and liver-function alteration. Leflunomide/teriflunomide may serve as an agent of importance to achieve faster virological clearance in COVID-19, however, findings needs to be validated in bigger sized placebo controlled studies.

In Vitro Characterization of Poly(Lactic Acid)/ Poly(Hydroxybutyrate)/ Thermoplastic Starch Blends for Tissue Engineering Application.

Complex in vitro characterization of a blended material based on Poly(Lactic Acid), Poly(Hydroxybutyrate), and Thermoplastic Starch (PLA/PHB/TPS) was performed in order to evaluate its potential for application in the field of tissue engineering. We focused on the biological behavior of the material as well as its mechanical and morphological properties. We also focused on the potential of the blend to be processed by the 3D printer which would allow the fabrication of the custom-made scaffold. Several blends recipes were prepared and characterized. This material was then studied in the context of scaffold fabrication. Scaffold porosity, wettability, and cell-scaffold interaction were evaluated as well. MTT test and the direct contact cytotoxicity test were applied in order to evaluate the toxic potential of the blended material. Biocompatibility studies were performed on the human chondrocytes. According to our results, we assume that material had no toxic effect on the cell culture and therefore could be considered as biocompatible. Moreover, PLA/PHB/TPS blend is applicable for 3D printing. Printed scaffolds had highly porous morphology and were able to absorb water as well. In addition, cells could adhere and proliferate on the scaffold surface. We conclude that this blend has potential for scaffold engineering.

Real-world outcomes for a complete nationwide cohort of more than 3200 teriflunomide-treated multiple sclerosis patients in The Danish Multiple Sclerosis Registry.

OBJECTIVE: Teriflunomide is a once-daily, oral disease-modifying therapy (DMT) for relapsing forms of multiple sclerosis (MS). We studied clinical outcomes in a real-world setting involving a population-based large cohort of unselected patients enrolled in The Danish Multiple Sclerosis Registry (DMSR) who started teriflunomide treatment between 2013-2019. METHODS: This was a complete nationwide population-based cohort study with prospectively enrolled unselected cases. Demographic and disease-specific patient parameters related to treatment history, efficacy outcomes, and discontinuation and switching rates among other clinical variables were assessed at baseline and during follow-up visits. RESULTS: A total of 3239 patients (65.4% female) started treatment with teriflunomide during the study period, 56% of whom were treatment-naïve. Compared to previously treated patients, treatment-naïve patients were older on average at disease onset, had a shorter disease duration, a lower Expanded Disability Status Scale score at teriflunomide treatment start and more frequently experienced a relapse in the 12 months prior to teriflunomide initiation. In the 3001 patients initiating teriflunomide treatment at least 12 months before the cut-off date, 72.7% were still on treatment one year after treatment start. Discontinuations in the first year were due mainly to adverse events (15.6%). Over the full follow-up period, 47.5% of patients discontinued teriflunomide treatment. Sixty-three percent of the patients treated with teriflunomide for 5 years were relapse-free, while significantly more treatment-naïve versus previously treated patients experienced a relapse during the follow-up (p<0.0001). Furthermore, 85% of the patients with available data were free of disability worsening at the end of follow-up. CONCLUSIONS: Solid efficacy and treatment persistence data consistent with other real-world studies were obtained over the treatment period. Treatment outcomes in this real-world scenario of the population-based cohort support previous findings that teriflunomide is an effective and generally well-tolerated DMT for relapsing MS patients with mild to moderate disease activity.

Update on treatment in multiple sclerosis.

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system. In recent years, many disease-modifying therapies (DMT) have been approved for MS treatment. For this reason, a profound knowledge of the characteristics and indications of the available compounds is required to tailor the therapeutic strategy to the individual patient characteristics. This should include the mechanism of action and pharmacokinetic of the drug, the safety and efficacy profile provided by clinical trials, as well as the understanding of possible side effects. Moreover, the evolving knowledge of the disease is paving the way to new and innovative therapeutic approaches, as well as the development of new biomarkers to monitor the therapeutic response and to guide the clinician's therapeutic choices. In this review we provide a comprehensive overview on currently approved therapies in MS and the emerging evidence-based strategies to adopt for initiating, monitoring, and eventually adapting a therapeutic regimen with DMT.

Multiple sclerosis in a patient with cryopyrin-associated autoinflammatory syndrome: Evidence that autoinflammation is the common link.

The co-existence of an autoinflammatory syndrome with a demyelinating disorder is a very rare occurrence raising the question whether there is a pathophysiological connection between them. We describe the case of a man with symptoms of cryopyrin-associated periodic syndrome (CAPS) since infancy who later developed multiple sclerosis (MS). As CAPS was genetically confirmed, the inhibition of interleukin-1 (IL-1) with anakinra led to a swift resolution of the CAPS symptoms and also, in combination with teriflunomide, to a clinical and imaging improvement of MS. In vitro studies showed that, upon a CAPS flare, the patient's peripheral neutrophils released neutrophil extracellular traps (NETs) decorated with IL-1ß, while NET release was markedly decreased following anakinra-induced remission of CAPS. Taking into account the growing evidence on the involvement of IL-1ß in experimental models of MS, this rare patient case suggests that the role of neutrophils/NETs and IL-1ß in MS should be further studied.

Impacto económico de las nuevas terapias orales en esclerosis múltiple / Economic impact of the new oral treatments for multiple sclerosis

INTRODUCCIÓN: La esclerosis múltiple (EM) es una enfermedad crónica del sistema nervioso central que se caracteriza por la existencia de inflamación, desmielinización, gliosis y daño axonal. La introducción de dimetilfumarato y teriflunomida ha supuesto un aumento de las alternativas terapéuticas en la primera línea de tratamiento de la EM. El objetivo de este estudio fue evaluar el impacto económico de la incorporación de estas nuevas terapias orales en la Unidad de Referencia (CSUR) del Hospital Universitario Puerta de Hierro Majadahonda. MATERIAL Y MÉTODOS: Se realizó un estudio observacional retrospectivo en la población de pacientes diagnosticados de EM, en tratamiento con fármacos modificadores de la enfermedad durante el año 2015, y su seguimiento se prolongó hasta obtener un seguimiento medio superior a un año de tratamiento. Los datos se recogieron de la historia clínica electrónica y del programa de dispensación de medicamentos a pacientes externos y ambulantes del Servicio de Farmacia. RESULTADOS: Evaluando el coste del cambio del tratamiento en 125 pacientes desde otros fármacos a dimetilfumarato o teriflunomida y comparando con el coste que habría supuesto el mantenimiento de los tratamientos previos, el ahorro total durante el periodo de observación fue de 169.107,31 (Euro). CONCLUSIONES: Dimetilfumarato y teriflunomida, además de aportar nuevas alternativas terapéuticas, no solo no han supuesto un incremento sino, por el contrario, una disminución en los costes del tratamiento de la EM en nuestro hospital

INTRODUCTION: Multiple sclerosis (MS) is a chronic disease affecting the central nervous system and is characterised by inflammation, demyelination, gliosis, and axonal damage. The introduction of dimethyl fumarate and teriflunomide has led to an increase in the number of alternative first-line therapies for MS. The objective of this study was to evaluate the economic impact of the incorporation of new oral therapies at the reference unit (CSUR) at Hospital Universitario Puerta de Hierro Majadahonda. MATERIALS AND METHODS: We performed a retrospective observational study including patients diagnosed with MS, who underwent treatment with disease-modifying drugs in 2015 and were followed up for a minimum mean time of one year. Data were collected from patients' electronic clinical histories and the pharmacy service's programme for dispensing drugs to outpatients. RESULTS: Evaluating the cost of changing 125 patients' treatment from other drugs to dimethyl fumarate and teriflunomide, and comparing this with the cost that would have resulted from maintaining their previous treatment, demonstrated a total saving of (Euro)169,107.31 over the study period. CONCLUSIONS: In addition to contributing new therapeutic alternatives, dimethyl fumarate and teriflunomide produced an economic saving in MS treatment at our hospital