Thèses sur le sujet « Disease-modifying treatments »

Multiple sclerosis (MS) is an autoimmune disease affecting the central nervous system (CNS) that most commonly begins with a relapsing-remitting course (RRMS). Many disease modifying treatments now are available, but none have efficacy in all patients, all are expensive and all are associated with possible adverse events. Stratifying patients to the best tolerated and most efficacious treatment either prior to or soon after commencing treatment would enhance relative benefits and reduce harm. Effective stratification depends on an understanding of relevant aspects of a drug’s mechanism of action, characterisation of key pharmacodynamic effects and being able to monitor disease activity over time. In this study, I set out to determine whether multi-omics profiling (transcriptome, cytokines, lipoproteins and metabolome) can fulfil these three requirements for one of the newer, oral treatments for RRMS, dimethyl fumarate (DMF). Chapter 1 provides an introduction to MS and explores the need for a stratified approach to treatment. Chapter 2 outlines the materials and methods used in this study including a discussion of modelling approaches that are used for data reduction. In Chapter 3, I aimed to discriminate MS patients from healthy controls using multi-omics profiling. The RRMS patients showed greater expression of immune pathway genes, as well as raised concentrations of lipids within lipoprotein sub-fractions, relative to healthy controls. The lipid measures were predictive of disability as measured using the Expanded Disability Status Scale (EDSS) when combined in a multivariate regression model. In Chapter 4, I tested whether multi-omics profiling could further elucidate the pharmacodynamic actions of dimethyl fumarate (DMF), a disease modifying treatment for RRMS. Comparisons of patient samples pre- and 6 weeks post- initiation of DMF revealed transcriptome changes enriched for activation of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and inhibition of nuclear factor κB (NFκB). Metabolomics profiling defined elevated levels of tricarboxylic acid metabolites, fumarate, succinate, succinyl-carnitine and methyl-succinylcarnitine. In Chapter 5, I used my prospective longitudinal data to test whether gene expression and metabolite changes associated with drug action in the blood mononuclear cell fraction at 6 weeks are associated with clinical and radiological responses at 15 months. Patients responding to treatment (measured using the composite outcome measure ‘no evidence of disease activity’) showed robust transcriptome changes between baseline and 6-weeks that were not present in non-responders. They also showed a relative stabilisation of gene expression over the remaining study period. My study thus provides evidence that multi-omics profiling could be a useful tool for stratified medicine in MS. It promises to elucidate differences that exist between disease and healthy states, further understanding of the pharmacodynamics of treatments and can provide longitudinal measures of response for monitoring the impact of a medicine. The latter could be used to optimise treatment choice for individual patients. If these methods were reduced to practice they could increase the chances of better clinical outcomes whilst avoiding otherwise unnecessary adverse events.

Disease modifying therapies (DMTs) used in the treatment of relapsing remitting multiple sclerosis (RRMS) have broad effects on the immune system that are incompletely understood. There is great heterogeneity in treatment response to most DMTs. However, biomarkers predicting treatment response are lacking. In this thesis, the peripheral immune changes induced by treatment with two DMTs, fingolimod (FTY) and dimethyl fumarate (DMF), are examined in detail by immune phenotyping using multicolour flow cytometry. Chapter 3 presents a longitudinal study of T cell subsets in patients commencing treatment with DMF. Differential losses of T cell subsets are found, including relative changes in regulatory and effector subsets potentially relevant to the mechanism of action of DMF. DMF-induced lymphopaenia is further studied in an in vitro culture system. The study results suggest that differential susceptibility of distinct T cell subsets to DMF-induced apoptosis may underly differential T cell losses seen in treated patients. In Chapter 4, the effects of FTY on peripheral T cell subsets and the reversibility of these effects is explored in patients ceasing FTY treatment. Long-lasting alterations in circulating T cell subsets are documented, indicating that FTY-induced changes in the peripheral immune repertoire may persist beyond the time taken for clinical laboratory measures to normalise. Chapter 5 presents a longitudinal study of a broad range of immune cell subsets in patients commencing FTY. Changes in potentially disease-relevant immune cell subsets not previously examined in FTY-treated patients are documented. Using magnetic resonance imaging (MRI) and clinical information to assess disease activity in these patients, potential immune biomarkers of FTY treatment response are uncovered. This thesis expands on our understanding of the effects of MS DMTs on the peripheral immune repertoire and highlights the utility of immune phenotyping in exploring DMT mechanisms of action and treatment response biomarkers.

Objectives: Adherence to multiple sclerosis (MS) treatment is essential to optimize the likelihood of full treatment effect. This prospective, observational, single-center cohort study investigated adherence to fingolimod over the 2 years following treatment initiation. Two facets of adherence - implementation and persistence - were examined and compared between new and experienced users of disease-modifying treatments (DMTs). Materials and methods: Implementation rates were based on the proportion of days covered and calculated as percentages per half-yearly visits and over 2 years, captured through refill data, pill count, and self-report. Nonadherence was defined as taking less than 85.8% of prescribed pills. Implementation rates were classified as nonadherent (< 85.8%), suboptimally adherent (>= 85.8% but. 96.2%), and optimally adherent (>= 96.2%), including perfectly adherent (100%). Persistence, ie, time until discontinuation, was analyzed by Kaplan-Meier analysis. Reasons for discontinuation were recorded. Results: The cohort included 98 patients with relapsing MS, all of whom received a dedicated education session about their medication. Of these 80% were women, 31.6% had fingolimod as first DMT, and 68.4% had switched from other DMTs. The mean implementation rate over 2 years was 98.6% (IQR(1-3) 98.51%-98.7%) and did not change significantly over time; 89% of measurements were in the optimally adherent category, 45.6% in the perfectly adherent category. There was one single occurrence of nonadherence. New users of DMTs were 1.29 times more likely to be adherent than experienced users (OR 1.29, 95% CI 1.11-1.51; P < 0.001), but not more persistent. Nineteen of 98 patients discontinued fingolimod. Conclusion: The very high implementation rates displayed in this sample of MS patients suggest that facilitation by health care professionals in preserving adherence behavior may be sufficient for the majority of patients. Targeted interventions should focus on patients who are nonadherent or who stop treatment without intention to reinitiate.

Parkinson’s disease (PD) is characterised by a progressive loss of dopaminergic neurones from the SNpc, leading to numerous downstream changes in the basal ganglia circuitry. Overactivity of the glutamatergic subthalamonigral pathway may underlie this continual degeneration of the nigrostriatal system. With this in mind, this thesis examined whether selective activation of group III metabotropic glutamate receptor subtypes may offer a novel strategy to halt persistent degeneration in PD. Initial distribution studies revealed mGlu4 and 7 group III mGlu receptor subtypes, demonstrated particularly intense immunoreactivity in the SNpc, suggesting these receptors may be ideally positioned to provide neuroprotective effects. Therefore, the first objective was to confirm this neuroprotective possibility using a broad spectrum agonist, L-AP4. Sub-chronic supranigral L-AP4 treatment mediated functional neuroprotection against a unilateral 6-OHDA lesion of the SN, confirmed by behavioural assessment and post-mortem analyses. Secondly, the pharmacological identity of the group III mGlu receptor mediating this protective effect was examined. To investigate mGlu4 receptors, the novel mGlu4 selective PAM VU0155041, was also shown to provide functional neuroprotection in the 6-OHDA rat model to an almost comparable level reached with L-AP4. Whilst these neuroprotective effects are likely mediated by an inhibition of glutamate to protect from glutamate-mediated excitotoxicity, VU015504 also led to a significant reduction in levels of GFAP and IBA-1 suggesting an additional anti-inflammatory action. Further studies revealed little evidence for co-localisation of mGlu4 receptors with GFAP in the SN suggesting this anti-inflammatory component likely reflects an indirect effect via stimulation of neuronal mGlu4 receptors. Finally, to investigate mGlu7 receptors, the selective allosteric agonist AMN082, was also shown to protect the nigrostriatal tract and demonstrate a degree of preservation of motor function. In contrast, mGlu8 receptor activation using the selective agonist DCPG, failed to protect the nigrostriatal tract or preserve motor behaviour. Collectively, these findings demonstrate that, of the group III mGlu receptors investigated, mGlu4 offers the most potential as a promising target for establishing disease modification in PD.

Public health aspects of pharmaceutical prescription patterns: Exemplified by treatments for prevention of cardiovascular disease. Louise Silwer. ISBN: 978-91-85721-18-4 ISSN: 0283-1961Main aim:To study patterns and trends of dispensed prescriptions, to explore what proportion of the population is exposed to some of the more prevalently prescribed pharmaceuticals, and to find possible ways of measuring drug-induced adverse symptoms in the population. Further, to illuminate conditions surrounding prescribing in primary prevention of cardiovascular disease. Methods: In three descriptive studies of prescription patterns, prescription data at aggregate level from a Swedish county were analysed retrospectively, and proportions were calculated. Data from the first ten years of the studies were obtained from a local prescription study, and data from another five years were local data from a national prescription survey. Data from a Danish database (OPED), with data at the individual level, were used for a prescription sequence symmetry analysis, and when Swedish national prescription data at the individual level became accessible, they were used for calculations of drug prevalence in the entire Swedish population. In a qualitative analysis of interview data, a phenomenographic approach was used. Main results: The purchase of pharmaceuticals on prescription almost doubled in the studied county in the period 1988-2002. Some common pharmaceuticals that increased to a great extent among the older part of the population were cardiovascular preventive drugs, such as antihypertensive and lipid modifying agents, and also hormone replacement therapy for women. In 2005, over half of all Swedish citizens, aged 60 or over, purchased antihypertensive or lipid modifying preparations during a six-month period. The different views that were found among GPs, regarding beliefs and practical management of primary prevention of CVD, could be interpreted as a reflection of the complexity of patient counselling in primary prevention in practice. Conclusion: The increase in dispensed prescriptions over the 15 years and the magnitude of the prevalence of the studied pharmaceuticals, such as antihypertensive, lipid modifying and hormonal treatments, which to a great extent are used by ‘healthy’ people, point to the need of following-up both beneficial and harmful consequences on public health. The prevalence of preventive treatments together with the variation in views of administration of primary prevention of cardiovascular disease, also point to the need of clarification of guidelines regarding pharmaceutical primary prevention and encouragement of therapy discussions among GPs.

Osteoarthritis (OA) is a common group of disabling joint disorders for which there are limited pharmacological therapies to alter disease progression. Zoledronate, one of several bisphosphonates found to modulate joint changes in animal OA models, may have a disease-modifying role, and potential mechanisms of action include effects on cartilage and/or subchondral bone. In OA cartilage, loss of aggrecan, the main glycosaminoglycan-bearing proteoglycan, and degradation of type II collagen are major biochemical changes arising from imbalances in matrix synthesis and degradation. Zoledronate, in common with other bisphosphonates, is capable of inhibiting matrix metallo-proteinases, enzymes implicated in OA cartilage matrix catabolism, providing a biochemical basis for cartilage effects but it is not known whether direct effects occur at the cell/tissue level. Studies described in this thesis have explored the hypothesis that zoledronate modifies cartilage metabolism to reduce cartilage glycosaminoglycan loss in OA. Short-term treatment effects on proteoglycan synthesis and degradation were examined in vitro in models of cartilage and chondrocyte metabolism, with IL-1a used to stimulate "OA-like" tissue glycosaminoglycan release. Zoledronate 10M adversely affected cell viability, proliferation and proteoglycan synthesis in bovine articular chondrocytes and, thus, was the upper limit of the concentration range investigated. No enhancing effects were observed with zoledronate 10"10M to 10/1 on proteoglycan synthesis in bovine articular chondrocytes. No effects on glycosaminoglycan release were seen with zoledronate 10"10M to 10"5M in bovine articular cartilage or with zoledronate 10"8M to "10M in alginate bead constructs containing bovine articular chondrocytes and matrix. Thus, a direct effect on cartilage proteoglycan metabolism following short-term treatment does not appear to be a mechanism of action for zoledronate as a disease-modifying treatment in OA. However, preventative or delayed treatment effects remain unaddressed and other potential targets for zoledronate in the OA joint include cartilage type II collagen metabolism and subchondral bone metabolism.

L’objectif de la thèse était d’étudier l’influence des déterminants socio-économiques dans l’évolution et la prise en charge thérapeutique de la Sclérose en Plaques (SEP). Dans une 1ère partie, nous avons réalisé une revue de la littérature afin d’identifier l’association entre les déterminants socio-économiques et risque de développer une SEP. Les études les plus récentes, de bon niveau méthodologique, sur de grandes cohortes de patients mettent en avant qu’un faible niveau socio-économique serait associé à un risque plus élevé de développer une SEP. Dans une 2ème partie, nous avons étudié l’influence des déterminants socio-économiques sur le risque d’atteindre des niveaux de handicap modérés (EDSS 4) et sévères (EDSS 6) chez des patients atteints de SEP récurrente-rémittente (SEP-RR) et secondairement progressive (SEP-SP), inclus dans les bases de données de 3 centres expert SEP de l’Observatoire Français de la SEP (OFSEP), Caen, Rouen et Lille (N=3641). Comme indicateur du niveau socio-économique, nous avons utilisé l’EDI, un indice agrégé et écologique de défavorisation socio-économique. Le risque d’atteindre un EDSS 4 ou un EDSS 6 était significativement plus important chez les patients les plus défavorisés socio-économiquement (EDI-quintile 5) que chez les patients les plus favorisés (EDI-quintile 1) ; Hazard Ratio ajusté HRa=1.37 [1.15-1.64] pour le risque d’atteindre un EDSS 4 et HRa=1.42 [1.13-1.75] celui d’atteindre un EDSS 6.Enfin, dans une 3ème partie, nous avons étudié l’influence des déterminants socio-économiques approchés par l’EDI sur la prise en charge thérapeutique et plus spécifiquement l’accès aux traitements de fond (DMT), en prenant en considération l’accès au 1er DMT des patients SEP-RR et -SP inclus dans les bases de données des 3 mêmes centres de l'OFCE (N=3293) puis l’accès aux DMT de 2nde ligne (Cyclophosphamide, Mitoxantrone, Natalizumab, et Fingolimod) des patients SEP-RR de la base de donnée régionale de la Normandie Occidentale (N=733). D’après nos résultats il semble que les déterminants socio-économiques n’influencent pas l’accès aux 1er DMT. Cependant nous avons montré une influence des déterminants socio-économiques sur l’accès aux DMT de 2nde ligne. En effet, partir de 5 ans d’exposition à un 1er DMT, la probabilité de recevoir un DM de 2nde ligne est 3 fois plus élevée pour les patients socio-économiquement les plus favorisés (EDI-quintile 1) comparé aux patients avec des EDI plus élevés (EDI-quintiles 2 à 5) HRa=3.14 [1.72-5.72]. Nous avons mis en évidence que les déterminants socio-économiques influençant plusieurs moments clefs de l’évolution de la maladie et de la prise en charge thérapeutiques des patients SEP. Ces observations devraient encourager les neurologues et les équipes paramédicales à prendre des dispositions afin d’améliorer la prise en charge des patients socio-économiquement vulnérables en cherchant à réduire l’impact de ces inégalités sociales de santé (ISS) sur l’évolution de la SEP et l’accès aux soins
The general objective of the thesis was to study the influence of socio-economic determinants in Multiple Sclerosis (MS) evolution and therapeutic health care. In a 1st part, we performed a review of the literature, to identify the association between socio-economic déterminants and MS risk. The most recent studies performed with solid methodology on large cohort show that low socio-economic status seems to be associated with a higher risk of Multiple Sclerosis. In a 2nde part, we assessed the influence of socioeconomic deprivation on the risk to reach a moderate disability level (EDSS 4) and a severe disability level (EDSS 6) in RR-MS and SP-MM patients included in the databases of 3 MS expert centres (Caen, Rouen, Lille) of the French Observatory for MS (OFSEP) (N=3641). The EDI (European Deprivation Index), an ecological and aggregated indicator was used as an indicator of socio-economic level. The risk of reaching EDSS 4 and EDSS 6 for more socioeconomically deprived patients (EDI Q5) was independently higher than in the less socioeconomically deprived patients (EDI Q1), adjusted Hazard Ratio HRa=1.37 [1.15-1.64] to reach EDSS 4 and HRa=1.42 [1.13-1.75] to reach EDSS 6. Finally, in a 3rd part, we studied the influence of socio-economic determinants approached by the EDI on therapeutic health care, and specifically on the access to disease modifying treatments (DMT), taking into consideration the access to first DMT in RR-MS and SP-MS patients included in databases of the 3 same OFSEP centres (N=3293), then on the access to 2nde line DMT (Cyclophosphamide, Mitoxantrone, Natalizumab, and Fingolimod) in RR-MS patients, included in the regional database of Western-Normandy (N=733). According our results, socio-economic determinants do not seem to influence the access to a 1st DMT. However, we showed an influence of socio-economic determinants on the access to 2nde line DMT. Indeed, after 5 years from initiation of a first DMT the risk of accessing a 2nd line DMT is 3 times higher for patients with lower deprivation indices (1st quintile of EDI) HRa= 3.14 95%CI [1.72-5.72] compared to patients with higher values (EDI quintiles 2 to 5). We highlighted that socio-economic determinants influenced many key moments in evolution and therapeutic health care of MS patients. These observations encourage neurologist and paramedical team to take every provision to improve health care of socio-economically vulnerable MS patients and keep working to reduce social inequalities of health on evolution and access to care in MS

Investigation of the T-cell receptor (TCR) repertoire in patients with Relapsing-Remitting Multiple Sclerosis (RRMS) before and after two effective immunomodulatory treatments: Natalizumab (NTZ) and autologous hematopoietic stem cell transplantation (AHSCT). The TCR repertoire was investigated on peripheral T-cell subpopulations (naive and memory) by TCRbeta sequencing and, therefore, with high-dimensional bioinformatic analysis.

Cystic fibrosis (CF) is an autosomal recessive disorder due to mutations in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene leading to abnormality of chloride channels in mucus and sweat producing cells. Respiratory and gastrointestinal systems are primarily involved but eventually multiple organs are affected leading to life threatening complications. Genetic mutations in CFTR affect its synthesis, processing, and transport to the plasma membrane and/or impede its function as a chloride channel and conductance regulator. Research is proceeding on multiple fronts including inhalational agents, anti-inflammatory treatments, and pancreatic replacement therapies. Furthermore, improved understanding of the molecular mechanisms that lead to CFTR dysfunction has stimulated the design of therapeutic strategies aimed at restoration of CFTR function. The recent approvals of ivacaftor and lumacaftor represent the genesis of a new era of precision medicine in the treatment of this condition. These drugs are having a positive impact on the lives of people with cystic fibrosis and are potentially disease modifying. This thesis focuses on existing knowledge about CF with emphasis on the basic defect of the disease and the current standard of care. Recent and noteworthy papers were collected and synthesized. Current treatments were examined for specificity and success in reducing symptoms.

The project described in this thesis began with a broad analysis of the changes to amino acid and biogenic amine concentrations in the central nervous system (CNS) during experimental autoimmune encephalomyelitis (EAE) in mice, an animal model of Multiple Sclerosis (MS). That study identified deficits in specific neurotransmitters during EAE that I targeted pharmacologically using the antidepressant drug phenelzine. Phenelzine administration substantially influenced the concentrations of amino acids and biogenic amines in EAE mice in a manner likely to be therapeutic. In the final experiment, I treated EAE mice chronically with phenelzine; This treatment was associated with significant improvements in motor abilities compared to vehicle treated animals. In an open field, improvements were also observed in behavioural indices of depression, physical sickness and anxiety. The results of this thesis may offer new insights into the pathogenesis of EAE and MS and indicate the disease-modifying potential of phenelzine treatment in MS.

A doença de Alzheimer representa uma das principais causas de morbilidade a nível mundial. É o tipo de demência com maior prevalência globalmente, cuja incidência tem aumentado devido ao envelhecimento populacional. Apesar dos avanços tecnológicos no diagnóstico e da constante investigação nesta área, a procura de um tratamento curativo constitui um dos maiores desafios da atualidade, na área da saúde. As estratégias atuais para o tratamento da doença de Alzheimer têm como principal alvo a sintomatologia, retardando apenas o desenvolvimento desta patologia. Assim, tendo em conta esta limitações, várias equipas de investigação reúnem esforços na busca de terapêuticas modificadoras da doença que atuem nos principais processos fisiopatológicos. A presente dissertação tem como objetivo realizar uma revisão bibliográfica relativamente ao tratamento atual na doença de Alzheimer e das perspetivas futuras, realçando os novos compostos em estudo, baseados na investigação diferencial que surgiu nos últimos anos e que têm como objetivo ultrapassar as limitações atuais e suprir a necessidade de novas terapêuticas modificadoras da doença.
Alzheimer's disease represents one of the leading causes of morbidity worldwide. It’s the type of dementia with the biggest prevalence globally, and the incidence has increased due to the aging population. Despite technological advances in diagnosis and constant research in this area, the search for a curative treatment is one of the biggest challenges in the health area today. Current strategies for the treatment of Alzheimer's disease have as their main target symptomatology, delaying only the development of this pathology. Thus, taking into account these limitations, several research teams join forces in the search for diseasemodifying therapies that act in the main pathophysiological processes. The present dissertation aims to carry out a bibliographic review in relation to the current treatment in Alzheimer's disease and future perspectives, highlighting the new compounds under study, based on the differential research that has emerged in recent years and which aim to overcome current limitations and supply the need for new diseasemodifying therapies.

Trabalho de Projeto do Mestrado Integrado em Medicina apresentado à Faculdade de Medicina
O tratamento da Esclerose Múltipla Forma Surto Remissão (EMSR) é um desafio, não só pela pluralidade de fármacos modificadores de doença (DMTs) disponíveis em formulações orais e injetáveis, mas também pela necessidade do cumprimento do regime terapêutico dado o cariz crónico da doença. Os DMTs injetáveis, mais antigos, estão associados a um melhor perfil de segurança a curto e longo prazo, com benefício demonstrado na estabilidade da doença e custo mais favorável. Têm, contudo, a desvantagem inerente às formulações injetáveis com dor e reações cutâneas no local da injeção, bem como outros efeitos sistémicos indesejáveis como a síndroma pseudo-gripal no caso dos interferões beta. Os novos fármacos orais de primeira linha têm a comodidade da via de administração, mas estão associados a efeitos secundários tais como alterações gastrointestinais e hematológicas com repercussões sistémicas. O objetivo deste trabalho consiste em avaliar a adesão terapêutica entre formulações injetáveis e orais em doentes com EMSR, identificando preditores de insuficiente adesão ao tratamento.Métodos: Estudo observacional, que incluiu doentes com EMSR, com idade superior a 18 anos, seguidos na consulta de Doenças Desmielinizantes, sob tratamento de primeira linha injetável ou oral, que adquirem a sua medicação nos Serviços Farmacêuticos do Centro Hospitalar e Universitário de Coimbra (CHUC). Após o consentimento informado, foram aplicados questionários e recolhidos dados provenientes do processo clínico e dos registos informáticos relativos aos dados demográficos, clínicos e medicação na Farmácia Hospitalar. O estudo foi previamente submetido e aprovado pela Comissão de Ética do CHUC.Resultados: Foram incluídos 60 doentes, dos quais 56.67% (n=34) estavam sob formulações injetáveis de primeira linha. A adesão global avaliada por questionário face ao cumprimento do regime terapêutico nas 4 semanas que antecederam o preenchimento do questionário foi de 85.5% (n=51), sendo que se registaram valores superiores de forma não significativa no grupo dos orais face ao dos injetáveis, de 88.46% e 82.35%, respetivamente. Bons níveis de adesão terapêutica (valores de ratio de posse de medicamento (MPR) ≥80%) foram registados em 93.33% (n=56) dos participantes, sem diferenças significativas entre grupos. Foram registados efeitos adversos associados diretamente com a administração do tratamento prescrito em cerca de 61.65% dos casos, sem diferenças significativas entre os dois grupos (67.65% no grupo de DMT injetável vs. 53.85% no grupo DMT oral, p=0.276). Conclusão: Globalmente, a adesão aos fármacos modificadores de primeira linha, tanto nas formulações injetáveis como orais, nos doentes seguidos em consulta no CHUC, é muito boa, reforçando o acompanhamento dos doentes com EMSR e a sua educação sobre a história natural da doença, a existência de expetativas realistas relativamente ao tratamento, informação e gestão dos efeitos adversos associados à terapêutica.
The long-term therapy of Relapsing-remitting Multiple Sclerosis (RRMS) can be challenging, not only due to the several disease-modifying therapies (DMTs) available but also because of the chronic nature of the disease. Self-injectable DMTs have historically been the most commonly used DMT and are associated with better safety and clinical stability profile at short and long term therapy and economic outcomes. Nevertheless, common barriers to adherence with injectable DMTs include adverse events like injection-site reactions and other systemic effects such as flu-like symptoms with Interferon beta. In recent years, newer oral DMTs have been approved for the treatment of MS and they will generate much interest because of the convenience of such administration, but common gastrointestinal and haematological adverse events with systemic repercussions are associated. The aim of this article was to compare adherence to DMTs in patients with MS treatment with an injectable versus an oral DMT and to identify which factors most influenced nonadherent behaviour.Methods: This observational database study included patients with RRMS if they were at least 18 years of age at the time of enrolment, on monotherapy with their current injectable or oral DMT, followed in Demyelinating Diseases’ appointments and who take their DMTs from the pharmacy of our hospital - Centro Hospitalar e Universitário de Coimbra (CHUC). After the local hospital ethics committee granted approval to conduct this observational study, patients received paper questionnaires regarding adherence to DMTs and data on MS patients’ demographics, clinical characteristics, disability measures and pharmacy claims data were collected.Results: The analysis included 60 patients, of whom 56.67% (n=34) were treated with first line injectable DMTs. The global adherence was measured by questionnaires based on the therapeutic regime of the previous four weeks was of 85.5% (n=51), but higher results were reported without significant differences for oral DMT compared to injectable DMT, of 88.46% and 82.35%, respectively. Good levels of therapeutic adherence (values of medication possession ratio (MPR) ≥80%) were observed in 93.33% (n=56) of the patients and did not differ significantly between groups of DMTs. Adverse events were reported in 61.65% of the patients, without significant between-treatment differences (67.65% with injectable DMTs vs. 53.85% with oral DMTs, p=0.276). Conclusions: Globally, this study has shown optimal adherence to injectable disease-modifying first-line therapies and so in oral routes of administration in patients followed in appointments in CHUC, supporting the need of the close monitoring of the patients with EM, their education about the natural history of the disease and the evidence of realistic expectations upon the current treatment, information and management of the associated adverse events.