Search

In this review, we critically summarize recent findings derived from randomized controlled trials (RCTs), observational studies and meta-analyses that have been published in the last 3years and that included the effects of DMTs on cognitive performances among their outcomes.

Made available in DSpace on 2021-06-25T11:14:59Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-05-01 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Dysbiosis, associated with barrier disruption and altered gut–brain communications, has been associated with multiple sclerosis (MS). In this study, we evaluated the gut microbiota in relapsing–remitting patients (RRMS) receiving disease-modifying therapies (DMTs) and correlated these data with diet, cytokines levels, and zonulin concentrations. Stool samples were used for 16S sequencing and real-time PCR. Serum was used for cytokine determination by flow cytometry, and zonulin quantification by ELISA. Pearson’s chi-square, Mann–Whitney, and Spearman’s correlation were used for statistical analyses. We detected differences in dietary habits, as well as in the gut microbiota in RRMS patients, with predominance of Akkermansia muciniphila and Bacteroides vulgatus and decreased Bifidobacterium. Interleukin-6 concentrations were decreased in treated patients, and we detected an increased intestinal permeability in RRMS patients when compared with controls. We conclude that diet plays an important role in the composition of the gut microbiota, and intestinal dysbiosis, detected in RRMS patients could be involved in increased intestinal permeability and affect the clinical response to DTMs. The future goal is to predict therapeutic responses based on individual microbiome analyses (personalized medicine) and propose dietary interventions and the use of probiotics or other microbiota modulators as adjuvant therapy to enhance the therapeutic efficacy of DMTs. Microbiome Study Group School of Health Sciences Dr. Paulo Prata Microbiology Program Institute of Biosciences Humanities and Exact Sciences São Paulo State University DNA Consult Genetics and Biotechnology Barretos Cancer Hospital Department of Technology School of Agricultural and Veterinarian Sciences São Paulo State University (UNESP) Biotechnology Department Sao Carlos Federal University Food Engineering and Technology Department São Paulo State University (UNESP) Microbiology Program Institute of Biosciences Humanities and Exact Sciences São Paulo State University Department of Technology School of Agricultural and Veterinarian Sciences São Paulo State University (UNESP) Food Engineering and Technology Department São Paulo State University (UNESP) FAPESP: 2016/05062-2 FAPESP: 2016/50204-0 FAPESP: 2017/04508-0 FAPESP: 2021/03866-5

Background: Multiple Sclerosis (MS) is one of the most common causes of neurological disability in young and middle-aged adults. Patients with MS face many challenges, both physical and emotional, and see an overall reduction in their autonomy. There is no definitive treatment for MS, though Disease Modifying Drugs (DMDs) have proved effective in reducing the frequency and severity of relapses. Unfortunately, long-term adherence to these therapies is a significant challenge due to practical difficulties as well as a general distrust towards the drugs . Objective: This study follows an original research carried out in 2008. In the first study, patients answered questions on their clinical history and expressed their judgment on the pharmacological treatment, their perceived effectiveness and factors that may undermine compliance. They have been recalled after two years to verify if the reported symptoms have changed and to assess how their knowledge of the disease and “acceptance” of the treatment have been modified. Methods: In spite of the relatively high number of patients participating in the first study (141 patients followed at a single neurological centre), only 16 patients have completed the questionnaire for the long-term survey. A detailed descriptive analysis has been carried out, as well as a pairwise correlation analysis. Results and Conclusions: The interviews carried out gave an insight into how patients’ behavior may have changed over time. Compliance rate is different in newly-diagnosed patients and long-term patients; the latter are more likely to be compliant, given their personal experience with the disease. Communications with neurologists and health personnel should aim at forming therapeutic alliances with patients and detecting their preferences for a qualitatively adequate assistance throughout their illness.

Osteoarthritis (OA) is currently the most widespread musculoskeletal condition and primarily affects weight-bearing joints such as the knees and hips. Importantly, knee OA remains a multifactorial whole-joint disease, the appearance and progression of which involves the alteration of articular cartilage as well as the synovium, subchondral bone, ligaments, and muscles through intricate pathomechanisms. Whereas it was initially depicted as a predominantly aging-related and mechanically driven condition given its clear association with old age, high body mass index (BMI), and joint malalignment, more recent research identified and described a plethora of further factors contributing to knee OA pathogenesis. However, the pathogenic intricacies between the molecular pathways involved in OA prompted the study of certain drugs for more than one therapeutic target (amelioration of cartilage and bone changes, and synovial inflammation). Most clinical studies regarding knee OA focus mainly on improvement in pain and joint function and thus do not provide sufficient evidence on the possible disease-modifying properties of the tested drugs. Currently, there is an unmet need for further research regarding OA pathogenesis as well as the introduction and exhaustive testing of potential disease-modifying pharmacotherapies in order to structure an effective treatment plan for these patients.

Background: In patients with multiple sclerosis (MS), non-adherence to disease-modifying drug therapy is associated with an increased rate of MS relapses. Early identification of patients at risk of non-adherence would allow provision of timely and individualized support. The aim of the BETAPREDICT study was to investigate potential predictors of adherence in patients with MS in Germany treated with interferon β-1b (IFNβ-1b) using the BETACONNECT® autoinjector.Methods: BETAPREDICT was a national, multi-center, prospective, non-interventional, single-arm, 24-month cohort study of patients with relapsing–remitting MS or clinically isolated syndrome receiving IFNβ-1b via the BETACONNECT® autoinjector (ClinicalTrials.gov: NCT02486640). Injection data were captured by the autoinjector. The primary objective was to determine baseline predictors of compliance, persistence, and adherence to IFNβ-1b treatment after 12- and 24 months using multivariable-adjusted regression. Secondary objectives included evaluation of satisfaction with the autoinjector, injection site pain, vitamin and nutrient supplementation, clinical course, and patient-related outcome measures.Results: Of 165 patients enrolled, 153 were available for analysis (120 with autoinjector data). Seventy-two patients left the study prematurely. Compliance (N = 120), persistence (N = 153), and adherence (N = 120) at 24 months were 89.1, 53.6, and 41.7%, respectively. Compliance at 12- and 24 months was predicted by intake of vitamin D supplements and absence of specific injection site reactions. Positive predictors of persistence included age (at 12- and 24 months) and previous duration of treatment (at 12 months), while intake of vitamins/nutrients other than vitamin D was a negative predictor (at 12 months). Positive predictors of adherence at 24 months were age and being experienced with IFNβ-1b. Higher scores in specific SF-36 subscales were positive predictors of medication-taking behavior at 24 months. Satisfaction with the autoinjector was high at baseline and 24 months (median score: 9 out of 10).Conclusions: Compliance with IFNβ-1b treatment among participants still under observation remained high over a 24-month period, while persistence and adherence continuously declined. Multiple factors affected medication-taking behavior, including patient characteristics, treatment history, injection site reactions, patients' perception of their health and support programs. The importance of these factors may differ among patients according to their individual situation.

International audience; Multiple sclerosis (MS) is usually diagnosed between twenty and forty years of age, when people often plan to have children. A lot has been said about the effect of pregnancy on the course of MS. The individual factors responsible for the disease modifying effect of pregnancy are not well determined. Having MS neither affects the fertility or the course of pregnancy itself. During pregnancy, many women find that their symptoms stay the same or even improve. Epidural and spinal analgesia appear to be safe and in general are not contraindicated for patients with MS. The management of disease-modifying treatments (DMTs) in pregnancy is a new issue for consideration in the clinical practice. There is limited information available into the safety of DMT use during pregnancy, especially for the most recent ones. In general, discontinuation of DMTs is recommended before conception to minimize risk of fetal harm. Women with very active MS before pregnancy who stop second-line treatments may show an increase in disease activity during pregnancy. Therefore, it might be discussed to maintain patients on DMTs until pregnancy is confirmed, and sometimes throughout pregnancy, to avoid a rebound of disease activity and severe relapses during pregnancy in very active patients.

Background: Gaps in current product labels and a lack of detailed clinical guidelines leaves clinicians’ questions on the practical management of patients receiving cladribine tablets for the treatment of relapsing multiple sclerosis (MS) unanswered. We describe a consensus-based programme led by international MS experts with the aim of providing recommendations to support the use of cladribine tablets in clinical practice. Methods: A steering committee (SC) of nine international MS experts led the programme and developed 11 clinical questions concerning the practical use of cladribine tablets. Statements to address each question were drafted using available evidence, expert experiences and perspectives from the SC and an extended faculty of 33 MS experts, representing 19 countries. Consensus on recommendations was achieved when ⩾75% of respondents expressed an agreement score of 7–9, on a 9-point scale. Results: Consensus was achieved on 46 out of 47 recommendations. Expert-agreed practical recommendations are provided on topics including: the definition of highly active disease; patterns of treatment response and suboptimal response with cladribine tablets; management of pregnancy planning and malignancy risk, infection risk and immune function, and switching to and from cladribine tablets. Conclusion: These expert recommendations provide up-to-date relevant guidance on the use of cladribine tablets in clinical practice.

Background: Women of child bearing age with multiple sclerosis (MS) must carefully consider treatments when planning a family, since disease modifying drugs (DMDs) are contraindicated during pregnancy. Objectives: This questionnaire-based study aimed to improve understanding of the effect of family planning on treatment decisions in female, Swiss MS patients. Methods: Female patients with MS (aged 18–55 years) participated in the 26-question survey between September 2014 and August 2015. Information captured included patient background, family planning status, treatment course, and previous pregnancies. Results: In total, 271 questionnaires distributed from 15 MS centres were returned for analysis. Of these, 250 (92.3%) participants received DMD therapy and 106 (39.1%) wanted children or were pregnant. Significantly more patients with a short-term plan to conceive within 2 years were treated with injectables (19/54) compared with those without a plan to conceive (19/108; p = 0.013). A proportionally greater number of women not planning to conceive took oral (34/108) or infusion therapies (41/108) compared with those with a short- (13/54 and 16/54, respectively) or medium-term (after 2 years or more; infusion therapy only, 14/44) plan to conceive. Conclusion: The study highlights that pregnancy remains an important yet unresolved concern in the treatment of MS patients. Nearly all women received DMD treatment, and type of DMD treatment was influenced by family planning, with significantly more women with a short-term plan to conceive using injectables.

Over the past 20 years, the available therapies for multiple sclerosis have expanded exponentially. With several more agents likely to be approved for public funding in Australia in the next 12 months on top of the existing multitude of Australian Pharmaceutical Benefits Scheme-subsidized therapies, the choice is becoming even more complex. This review summarizes the current state of available therapies and anticipates likely future directions, including an important focus on contemporary symptom management. For each agent, the major trials, side effects, and clinical utility are summarized, with a particular focus on the Australian experience of these therapies. It is hoped this review provides an up-to-date reference of the exciting current state of multiple sclerosis therapy.

Background The purpose of the survey was to assess the knowledge of family planning issues associated with disease modifying therapies (DMTs) among patients diagnosed with multiple sclerosis (MS). Methods 590 Danish MS patients responded to an online questionnaire about family planning in MS, collecting demographics, disease characteristics, disease modifying treatment, knowledge of potential teratogenic effects in DMTs, number of children, occurrence of unplanned pregnancies and outcome, and sources of information. Results 488 females and 102 males, mean age 40 years, responded. On average, it was 6.5 and 10.9 years since diagnosis and first symptoms, respectively. 16% of female and 19% of male respondents did not receive DMT at the time of responding to the survey. 30% of all had received only one DMT, 37%, 19%, 8%, and 5% had received two, three, four, and five different treatments, respectively. 42% of female and 74% of male respondents said they did not know if the medication they were taking had teratogenic risks. 83% of females and 85% of males responded that they did not know, whether DMT in male MS patients may expose healthy partners to teratogenic risks; hereto, 13% and 10%, respectively, answered that no transmission occurs. On average respondents had two children; three of four children reported in the study were born prior to the respondents being diagnosed with MS. 50% of both female and male respondents without children wanted a family and 25% of females and 16% of males wanted to start a family within the next two years. 91% of female respondents would discontinue DMT during pregnancy. Among male respondents 32% would continue treatment during a partner's pregnancy and 47% did not know whether they would continue or discontinue treatment. 10% of the female patients had had unplanned pregnancies during MS treatment, of these 49% chose to have an abortion. 53% of all felt they were well informed about MS treatment and family planning. 22% and 41% of the respondents received information from the neurologist about teratogenic risks in female MS patients and about teratogenic risks in women with male MS patients as partners, respectively; 27% and 34%% retrieved information from the internet on these two issues. Conclusion This survey uncovered a low level of knowledge about DMTs’ teratogenic risks among MS patients irrespective of sex. Knowledge about potential teratogenic risks for male MS patients receiving DMTs while planning to start a family was largely absent. 10% of female patients had experienced unplanned pregnancies on MS treatment. In general, patients use the internet and their neurologist to the same extent for information on parenthood planning.

Background Maintaining patient adherence to disease modifying drugs in multiple sclerosis is a challenge, which can be improved by autoinjectors. The BETACONNECT® is a fully electronic autoinjector for the injection of interferon beta-1b (IFN beta-1b) automatically recording injections. Methods The BETAEVAL study was a prospective, observational, cohort study over 24 weeks among patients with relapsing remitting multiple sclerosis or clinically isolated syndrome treated with IFN beta-1b in Germany using the BETACONNECT®. The primary aim was to investigate treatment adherence, secondary aims included assessing satisfaction and functional health status. Adherence was evaluated from injection data recorded by the device. Patient-related data were obtained from clinical examinations and patient questionnaires. Results Of the 151 patients enrolled, 143 were available for analysis. Thirty-four patients discontinued the study prematurely. 107/143 (74.8%) patients still used the BETACONNECT® at the end of the study. Injection data from the device at any visit was available for 107 patients. Among those, the percentage of adherent patients injecting ≥80% of doses and still participating in the study was 57.9% at week 24. 29% of patients prematurely stopped the study, 13.1% injected

Microvesicles (MVs) are released by immune cells especially of the myeloid lineage upon stimulation with ATP on its cognate receptor P2X7, both in physiological and pathological conditions. In Multiple Sclerosis (MS) the role of MVs remains little investigated. We aimed to compare the release of MVs in peripheral blood monocytes from MS patients with healthy donors (HDs) and to see how current MS treatment may affect such a production. We also assessed the treatment effect on M1 and M2 monocyte polarization and on the inflammasome components. Spectrophotometric quantification was performed to compare monocyte-derived microvesicles from 20 untreated relapsing-remitting MS patients and 20 healthy donors (HDs) and to evaluate the effect of different treatments. Subgroups of 9 IFNb and of 5 Teriflunomide treated MS patients were evaluated at baseline and after 2, 6 and 12 months of treatment. Six MS patients assuming Fingolimod, after switching from a first line therapy, were included in the study and analyzed only at 12 months of treatment. MVs analysis revealed that monocytes from MS patients produced vesicles in higher amounts than controls. All treatments reduced vesicle production but only Teriflunomide was associated with a down-regulation of P2X7R and inflammasome components expression. The therapies modulated mRNA expression of both M1 and M2 monocyte markers. Our results, suggesting new molecular targets for drugs currently used in MS, may potentially provide useful novel evidence to approach the disease.

Introdução: Poucos estudos avaliaram o perfil do uso de drogas modificadoras de doença (DMD) em pacientes brasileiros com diagnóstico de espondiloartrite (EpA). Métodos: Um protocolo comum de investigação foi prospectivamente aplicado em 1505 pacientes classificados como EpA pelos critérios do Grupo Europeu de Estudo das Espondiloartrites (ESSG), acompanhados em 29 centros de referência em Reumatologia no Brasil. Variáveis clínicas e demográficas foram obtidas e avaliadas, analisando-se suas correlações com o uso das DMD metotrexato (MTX) e sulfasalazina (SSZ). Resultados: Pelo menos uma DMD foi utilizada por 73,6% dos pacientes, sendo MTX por 29,2% e SSZ por 21,7%, enquanto 22,7% utilizaram ambas as drogas. O uso do MTX foi significativamente associado ao acometimento periférico, e a SSZ foi associada ao comprometimento axial, sendo que as duas drogas foram mais utilizadas, isoladas ou combinadas, no comprometimento misto (p < 0,001). O uso de uma DMD esteve significativamente associado à etnia branca (MTX; p = 0,014), lombalgia inflamatória (SSZ; p = 0,002), dor em nádegas (SSZ; p = 0,030), cervicalgia (MTX; p = 0,042), artrite de membros inferiores (MTX; p < 0,001), artrite de membros superiores (MTX; p < 0,001), entesite (p = 0,007), dactilite (MTX; p < 0,001), doença inflamatória intestinal (SSZ; p < 0,001) e acometimento ungueal (MTX; p < 0,001). Conclusão: O uso de pelo menos uma DMD foi referido por mais de 70% dos pacientes numa grande coorte brasileira de pacientes com EpA, sendo o uso do MTX mais associado ao acometimento periférico e o uso da SSZ mais associado ao acometimento axial. Introduction: Few studies have evaluated the profile of use of disease modifying drugs (DMD) in Brazilian patients with spondyloarthritis (SpA). Methods: A common research protocol was applied prospectively in 1505 patients classified as SpA by criteria of the European Spondyloarthropathies Study Group (ESSG), followed at 29 referral centers in Rheumatology in Brazil. Demographic and clinical variables were obtained and evaluated, by analyzing their correlation with the use of DMDs methotrexate (MTX) and sulfasalazine (SSZ). Results: At least one DMD was used by 73.6 % of patients: MTX by 29.2 % and SSZ by 21.7%, while 22.7 % used both drugs. The use of MTX was significantly associated with peripheral involvement, and SSZ was associated with axial involvement, and the two drugs were more administered, separately or in combination, in the mixed involvement (p < 0.001). The use of a DMD was significantly associated with Caucasian ethnicity (MTX , p = 0.014), inflammatory back pain (SSZ, p = 0.002) , buttock pain (SSZ, p = 0.030), neck pain (MTX, p = 0.042), arthritis of the lower limbs (MTX, p < 0.001), arthritis of the upper limbs (MTX, p < 0.001), enthesitis (p = 0.007), dactylitis (MTX, p < 0.001), inflammatory bowel disease (SSZ, p < 0.001) and nail involvement (MTX, p < 0.001). Conclusion: The use of at least one DMD was reported by more than 70% of patients in a large cohort of Brazilian patients with SpA, with MTX use more associated with peripheral involvement and the use of SSZ more associated with axial involvement.

No abstract available (Neurology)

IntroductionFew studies have evaluated the profile of use of disease modifying drugs (DMD) in Brazilian patients with spondyloarthritis (SpA).MethodsA common research protocol was applied prospectively in 1505 patients classified as SpA by criteria of the European Spondyloarthropathies Study Group (ESSG), followed at 29 referral centers in Rheumatology in Brazil. Demographic and clinical variables were obtained and evaluated, by analyzing their correlation with the use of DMDs methotrexate (MTX) and sulfasalazine (SSZ).ResultsAt least one DMD was used by 73.6% of patients: MTX by 29.2% and SSZ by 21.7%, while 22.7% used both drugs. The use of MTX was significantly associated with peripheral involvement, and SSZ was associated with axial involvement, and the two drugs were more administered, separately or in combination, in the mixed involvement (p < 0.001). The use of a DMD was significantly associated with Caucasian ethnicity (MTX, p = 0.014), inflammatory back pain (SSZ, p = 0.002), buttock pain (SSZ, p = 0.030), neck pain (MTX, p = 0.042), arthritis of the lower limbs (MTX, p < 0.001), arthritis of the upper limbs (MTX, p < 0.001), enthesitis (p = 0.007), dactylitis (MTX, p < 0.001), inflammatory bowel disease (SSZ, p < 0.001) and nail involvement (MTX, p < 0.001).ConclusionThe use of at least one DMD was reported by more than 70% of patients in a large cohort of Brazilian patients with SpA, with MTX use more associated with peripheral involvement and the use of SSZ more associated with axial involvement.

Optic neuritis (ON), a common manifestation of multiple sclerosis (MS), often occurs as the initial manifestation of central nervous system demyelination or develops during the course of this disease. Since the retinal nerve fiber layer (RNFL) is composed only of unmyelinated axons, measuring RNFL thickness represents a viable method of monitoring axonal loss in these patients. Optical coherence tomography (OCT) is a noninvasive, noncontact, accurate, and reproducible technique that quantitates the thickness of the peripapillary RNFL, fovea, and macula. Because of its potential role in defining axonal loss in ON and in assessing longitudinal changes in the RNFL before and after MS treatment, a multidisciplinary expert panel was charged with the following tasks: assess the current capabilities of OCT; review the current data about OCT, ON, and MS; and determine whether OCT could be a primary or secondary outcome measure in future MS clinical trials. The panel concluded that: [1] OCT is valid and reproducible; [2] OCT has yielded some important limited data concerning cross-sectional studies with ON and MS; [3] more studies are required to correlate OCT results with other measures of MS disease activity; [4] after correlation with these other measures and upon agreement of standardized technical and statistical methods, OCT may evolve into a important primary or secondary outcome metric for MS clinical trials and patient care.

Claudio Gasperini1, Serena Ruggieri2, Carlo Pozzilli21Department of Neurosciences, S Camillo Forlanini Hospital, Rome, Italy; 2Department of Neurological Sciences, University of Rome “La Sapienza”, ItalyAbstract: Multiple sclerosis (MS) is a chronic inflammatory disorder of the central ­nervous system (CNS) that represents one of the first causes of neurological disability in young adults. Although the pathogenesis of MS is still unclear, an autoimmune mechanism has been ­demonstrated. According to this evidence in the last 15 years different treatments acting on the immune system have been developed. Current disease-modifying drugs (DMDs) for MS require regular and frequent parenteral administration and are associated with limited ­long-term treatment adherence. Moreover the clinical efficacy of these disease-modifying drugs is ­suboptimal. Thus, there is an important need for the development of new therapeutic strategies. Several oral ­therapies (fingolimod, fumaric acid, teriflunomide, laquinimod) are in development; Among these cladribine is the only therapy with the potential for short-course dosing. Cladribine is an immunosuppressant that offers sustained regulation of the immune system through a preferential lymphocyte depleting action. Cladribine has a well-characterized and well-known safety profile, derived from more than 15 years of use of the parenteral formulation both in the oncology field and in MS. This paper reviews the new oral emerging treatments and presents the available data about the use of cladribine in MS and the future perspective of its clinical use.Keywords: multiple sclerosis, disease modifying drugs, oral therapy, treatment adherence, cladribine

Sulfasalazine is one of the main disease modifying drugs for the treatment of chronic inflammatory joint and spine diseases. The article describes mechanism of action of sulfasalazine and its main metabolites. Detailed information about anti-inflammatory and immunosuppressive action of the drug is presented. Results of many studies of sulfasalazine efficacy in rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis and reactive arthritis are discussed from the evidence based medicine point of view. Data on sulfasalazine tolerability and safety are presented with separate discussion of hypersensitivity and dose-dependent adverse reactions so as their treatment and prophylaxis.

Although fingolimod is registered in Europe for treatment of relapsing-remitting multiple sclerosis (RRMS) if earlier disease modifying therapy (DMT) has failed, no data regarding its efficacy in this patient group are available. This observational cohort study of the NeuroTransData network includes German RRMS outpatients with failure of earlier therapy with injectable DMT (iDMT), therefore switching to either another iDMT (n = 133) or to fingolimod (n = 300). Statistical comparison of clinical baseline characteristics showed more severely affected patients in the fingolimod group. A propensity-score matched group comparison was performed (n = 99 in each group) covering more than 2-year observation time. Fingolimod showed statistically significant superior efficacy in comparison to iDMT regarding annualized relapse rate (0.21 versus 0.33 per year), time-to-relapse and likelihood of relapse (iDMT hazard ratio 1.7), proportion and likelihood of patients with EDSS progression (15.10 versus 31.00 %; iDMT hazard ratio 1.7), persistence on medication and likelihood of discontinuation (iDMT hazard ratio 3.0). Significantly more patients were free of relapse and EDSS progression with fingolimod than with their second iDMT (64.4 versus 46.5 %, p