Base de dados : MEDLINE
Pesquisa : D12.644.219 [Categoria DeCS]
Referências encontradas : 1180 [refinar]
Mostrando: 1 .. 10   no formato [Detalhado]

página 1 de 118 ir para página                         

  1 / 1180 MEDLINE  
              next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28461106
[Au] Autor:Staun-Ram E; Miller A
[Ad] Endereço:Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
[Ti] Título:Effector and regulatory B cells in Multiple Sclerosis.
[So] Source:Clin Immunol;184:11-25, 2017 11.
[Is] ISSN:1521-7035
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The role of B cells in the pathogenesis of Multiple Sclerosis (MS), an autoimmune neurodegenerative disease, is becoming eminent in recent years, but the specific contribution of the distinct B cell subsets remains to be elucidated. Several B cell subsets have shown regulatory, anti-inflammatory capacities in response to stimuli in vitro, as well as in the animal model of MS: Experimental Autoimmune Encephalomyelitis (EAE). However, the functional role of the B regulatory cells (Bregs) in vivo and specifically in the human disease is yet to be clarified. In the present review, we have summarized the updated information on the roles of effector and regulatory B cells in MS and the immune-modulatory effects of MS therapeutic agents on their phenotype and function.
[Mh] Termos MeSH primário: Subpopulações de Linfócitos B/imunologia
Linfócitos B Reguladores/imunologia
Encefalomielite Autoimune Experimental/imunologia
Esclerose Múltipla/imunologia
[Mh] Termos MeSH secundário: Alemtuzumab/uso terapêutico
Animais
Crotonatos/uso terapêutico
Fumarato de Dimetilo/uso terapêutico
Cloridrato de Fingolimode/uso terapêutico
Acetato de Glatiramer/uso terapêutico
Seres Humanos
Fatores Imunológicos/uso terapêutico
Imunossupressores/uso terapêutico
Interferon beta/uso terapêutico
Esclerose Múltipla/tratamento farmacológico
Natalizumab/uso terapêutico
Rituximab/uso terapêutico
Toluidinas/uso terapêutico
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Crotonates); 0 (Immunologic Factors); 0 (Immunosuppressive Agents); 0 (Natalizumab); 0 (Toluidines); 1C058IKG3B (teriflunomide); 3A189DH42V (Alemtuzumab); 4F4X42SYQ6 (Rituximab); 5M691HL4BO (Glatiramer Acetate); 77238-31-4 (Interferon-beta); FO2303MNI2 (Dimethyl Fumarate); G926EC510T (Fingolimod Hydrochloride)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:180206
[Lr] Data última revisão:
180206
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170503
[St] Status:MEDLINE


  2 / 1180 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29320652
[Au] Autor:Reich DS; Lucchinetti CF; Calabresi PA
[Ad] Endereço:From the Translational Neuroradiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda (D.S.R.), and the Departments of Neurology and Neuroscience, Johns Hopkins School of Medicine, Baltimore (P.A.C.) - both in Maryland; and the Department of Neurology, Mayo Clinic, Rochester, MN (C.F.L.).
[Ti] Título:Multiple Sclerosis.
[So] Source:N Engl J Med;378(2):169-180, 2018 01 11.
[Is] ISSN:1533-4406
[Cp] País de publicação:United States
[La] Idioma:eng
[Mh] Termos MeSH primário: Encéfalo/patologia
Fatores Imunológicos/uso terapêutico
Esclerose Múltipla
[Mh] Termos MeSH secundário: Anticorpos Monoclonais/uso terapêutico
Biomarcadores
Acetato de Glatiramer/uso terapêutico
Seres Humanos
Interferon beta/uso terapêutico
Imagem por Ressonância Magnética
Esclerose Múltipla/diagnóstico por imagem
Esclerose Múltipla/tratamento farmacológico
Esclerose Múltipla/etiologia
Esclerose Múltipla/patologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T; REVIEW
[Nm] Nome de substância:
0 (Antibodies, Monoclonal); 0 (Biomarkers); 0 (Immunologic Factors); 5M691HL4BO (Glatiramer Acetate); 77238-31-4 (Interferon-beta)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180118
[Lr] Data última revisão:
180118
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:180111
[St] Status:MEDLINE
[do] DOI:10.1056/NEJMra1401483


  3 / 1180 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28829817
[Au] Autor:Brænne I; Zeng L; Willenborg C; Tragante V; Kessler T; Willer CJ; Laakso M; Wallentin L; Franks PW; Salomaa V; Dehghan A; Meitinger T; Samani NJ; Asselbergs FW; Erdmann J; Schunkert H; CARDIoGRAM Consortium; CARDIoGRAMplusC4D Consortium
[Ad] Endereço:Institute for Cardiogenetics, University of Lübeck, Lübeck, Germany.
[Ti] Título:Genomic correlates of glatiramer acetate adverse cardiovascular effects lead to a novel locus mediating coronary risk.
[So] Source:PLoS One;12(8):e0182999, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Glatiramer acetate is used therapeutically in multiple sclerosis but also known for adverse effects including elevated coronary artery disease (CAD) risk. The mechanisms underlying the cardiovascular side effects of the medication are unclear. Here, we made use of the chromosomal variation in the genes that are known to be affected by glatiramer treatment. Focusing on genes and gene products reported by drug-gene interaction database to interact with glatiramer acetate we explored a large meta-analysis on CAD genome-wide association studies aiming firstly, to investigate whether variants in these genes also affect cardiovascular risk and secondly, to identify new CAD risk genes. We traced association signals in a 200-kb region around genomic positions of genes interacting with glatiramer in up to 60 801 CAD cases and 123 504 controls. We validated the identified association in additional 21 934 CAD cases and 76 087 controls. We identified three new CAD risk alleles within the TGFB1 region on chromosome 19 that independently affect CAD risk. The lead SNP rs12459996 was genome-wide significantly associated with CAD in the extended meta-analysis (odds ratio 1.09, p = 1.58×10-12). The other two SNPs at the locus were not in linkage disequilibrium with the lead SNP and by a conditional analysis showed p-values of 4.05 × 10-10 and 2.21 × 10-6. Thus, studying genes reported to interact with glatiramer acetate we identified genetic variants that concordantly with the drug increase the risk of CAD. Of these, TGFB1 displayed signal for association. Indeed, the gene has been associated with CAD previously in both in vivo and in vitro studies. Here we establish genome-wide significant association with CAD in large human samples.
[Mh] Termos MeSH primário: Doenças Cardiovasculares/genética
Predisposição Genética para Doença
Acetato de Glatiramer/efeitos adversos
[Mh] Termos MeSH secundário: Doenças Cardiovasculares/induzido quimicamente
Estudos de Casos e Controles
Seres Humanos
Desequilíbrio de Ligação
Polimorfismo de Nucleotídeo Único
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
5M691HL4BO (Glatiramer Acetate)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171016
[Lr] Data última revisão:
171016
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170823
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0182999


  4 / 1180 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28661948
[Au] Autor:Newland P; Kimutis A; Salter A; Flick L; Thomas FP; Rantz M; Skubic M
[Ti] Título:Continuous In-Home Symptom and Mobility Measures for Individuals With Multiple Sclerosis: A Case Presentation.
[So] Source:J Neurosci Nurs;49(4):241-246, 2017 Aug.
[Is] ISSN:1945-2810
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Gait impairment represents one of the most common and disabling symptoms of multiple sclerosis (MS). To identify which temporal or spatial parameters of gait could be used as outcome measures in interventional studies of individuals with MS with different levels of disability, we evaluated characteristics of these parameters in a case study of 3 participants with MS, using 1 case as an exemplar and the other participants as validation. A case study of an exemplar participant was conducted with a 67-year-old woman with secondary progressive MS served as exemplar, with 2 other participants (52 and 55 years old) as validation. The primary outcome measures we used were stride time, stride length, gait velocity, and daily symptoms. Stride length and velocity of gait decreased with increasing pain and fatigue. The step time was significantly longer later in the day, whereas the step length remained the same. Stride length and velocity are associated with the level of fatigue and pain, as well as the time of day. These characteristics and parameters of gait need to be considered in future studies of gait in MS, with particular attention to temporality of occurrence in persons with MS.
[Mh] Termos MeSH primário: Transtornos Neurológicos da Marcha/terapia
Limitação da Mobilidade
Esclerose Múltipla/complicações
Amplitude de Movimento Articular/fisiologia
Equipamentos de Autoajuda/utilização
[Mh] Termos MeSH secundário: Adjuvantes Imunológicos/uso terapêutico
Idoso
Feminino
Transtornos Neurológicos da Marcha/etiologia
Acetato de Glatiramer/uso terapêutico
Seres Humanos
Masculino
Meia-Idade
Esclerose Múltipla/tratamento farmacológico
Andadores
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Adjuvants, Immunologic); 5M691HL4BO (Glatiramer Acetate)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170717
[Lr] Data última revisão:
170717
[Sb] Subgrupo de revista:IM; N
[Da] Data de entrada para processamento:170630
[St] Status:MEDLINE
[do] DOI:10.1097/JNN.0000000000000299


  5 / 1180 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28642148
[Au] Autor:Spadaro M; Montarolo F; Perga S; Martire S; Brescia F; Malucchi S; Bertolotto A
[Ad] Endereço:Neuroscience Institute Cavalieri Ottolenghi (NICO), Clinical Neurobiology Unit, Orbassano, Turin, Italy; AOU S. Luigi Gonzaga, Neurologia 2 - CReSM (Centro Riferimento Regionale Sclerosi Multipla), Orbassano, Turin, Italy. Electronic address: spadaro_michela@yahoo.it.
[Ti] Título:Biological activity of glatiramer acetate on Treg and anti-inflammatory monocytes persists for more than 10years in responder multiple sclerosis patients.
[So] Source:Clin Immunol;181:83-88, 2017 Aug.
[Is] ISSN:1521-7035
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Glatiramer acetate (GA) is a widely used treatment for multiple sclerosis (MS), with incompletely defined mechanism of action. Short-term studies suggested its involvement in the modulation of anti-inflammatory cytokines and regulatory T cells (Treg), while long-term effect is still unknown. To investigate this aspect, we analyzed by flow-cytometry peripheral-blood Treg, natural killer (NK), CD4 and CD8 T-cells and anti-inflammatory CD14 CD163 monocytes from 37 healthy donor and 90 RRMS patients divided in untreated, treated with GA for 12months and from 34 to 192months. While NK, CD4 and CD8 T-cells did not show any significant differences among groups over time, we demonstrated that GA increased the anti-inflammatory monocytes and restored the Treg level in both GA-treated groups. Both these effects are a characteristic of responder patients and are observed not just in short-term but even after as long as a decade of GA treatment.
[Mh] Termos MeSH primário: Acetato de Glatiramer/uso terapêutico
Imunossupressores/uso terapêutico
Monócitos/imunologia
Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico
Linfócitos T Reguladores/imunologia
[Mh] Termos MeSH secundário: Adulto
Idoso
Antígenos CD/metabolismo
Antígenos de Diferenciação Mielomonocítica/metabolismo
Linfócitos T CD4-Positivos/imunologia
Linfócitos T CD8-Positivos/imunologia
Estudos de Casos e Controles
Feminino
Seres Humanos
Células Matadoras Naturais/imunologia
Receptores de Lipopolissacarídeos/metabolismo
Meia-Idade
Monócitos/metabolismo
Esclerose Múltipla Recidivante-Remitente/imunologia
Receptores de Superfície Celular/metabolismo
Resultado do Tratamento
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antigens, CD); 0 (Antigens, Differentiation, Myelomonocytic); 0 (CD163 antigen); 0 (Immunosuppressive Agents); 0 (Lipopolysaccharide Receptors); 0 (Receptors, Cell Surface); 5M691HL4BO (Glatiramer Acetate)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170624
[St] Status:MEDLINE


  6 / 1180 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28572277
[Au] Autor:Stellmann JP; Krumbholz M; Friede T; Gahlen A; Borisow N; Fischer K; Hellwig K; Pache F; Ruprecht K; Havla J; Kümpfel T; Aktas O; Hartung HP; Ringelstein M; Geis C; Kleinschnitz C; Berthele A; Hemmer B; Angstwurm K; Young KL; Schuster S; Stangel M; Lauda F; Tumani H; Mayer C; Zeltner L; Ziemann U; Linker RA; Schwab M; Marziniak M; Then Bergh F; Hofstadt-van Oy U; Neuhaus O; Zettl U; Faiss J; Wildemann B; Paul F; Jarius S; Trebst C; Kleiter I; NEMOS (Neuromyelitis Optica Study Group)
[Ad] Endereço:Institut für Neuroimmunologie und Multiple Sklerose (INIMS), Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany.
[Ti] Título:Immunotherapies in neuromyelitis optica spectrum disorder: efficacy and predictors of response.
[So] Source:J Neurol Neurosurg Psychiatry;88(8):639-647, 2017 Aug.
[Is] ISSN:1468-330X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: To analyse predictors for relapses and number of attacks under different immunotherapies in patients with neuromyelitis optica spectrum disorder (NMOSD). DESIGN: This is a retrospective cohort study conducted in neurology departments at 21 regional and university hospitals in Germany. Eligible participants were patients with aquaporin-4-antibody-positive or aquaporin-4-antibody-negative NMOSD. Main outcome measures were HRs from Cox proportional hazard regression models adjusted for centre effects, important prognostic factors and repeated treatment episodes. RESULTS: 265 treatment episodes with a mean duration of 442 days (total of 321 treatment years) in 144 patients (mean age at first attack: 40.9 years, 82.6% female, 86.1% aquaporin-4-antibody-positive) were analysed. 191 attacks occurred during any of the treatments (annual relapse rate=0.60). The most common treatments were rituximab (n=77, 111 patient-years), azathioprine (n=52, 68 patient-years), interferon-ß (n=32, 61 patient-years), mitoxantrone (n=34, 32.1 patient-years) and glatiramer acetate (n=17, 10 patient-years). Azathioprine (HR=0.4, 95% CI 0.3 to 0.7, p=0.001) and rituximab (HR=0.6, 95% CI 0.4 to 1.0, p=0.034) reduced the attack risk compared with interferon-ß, whereas mitoxantrone and glatiramer acetate did not. Patients who were aquaporin-4-antibody-positive had a higher risk of attacks (HR=2.5, 95% CI 1.3 to 5.1, p=0.009). Every decade of age was associated with a lower risk for attacks (HR=0.8, 95% CI 0.7 to 1.0, p=0.039). A previous attack under the same treatment tended to be predictive for further attacks (HR=1.5, 95% CI 1.0 to 2.4, p=0.065). CONCLUSIONS: Age, antibody status and possibly previous attacks predict further attacks in patients treated for NMOSD. Azathioprine and rituximab are superior to interferon-ß.
[Mh] Termos MeSH primário: Imunoterapia/métodos
Neuromielite Óptica/tratamento farmacológico
[Mh] Termos MeSH secundário: Adulto
Aquaporina 4/imunologia
Autoanticorpos/sangue
Azatioprina/uso terapêutico
Estudos de Coortes
Feminino
Seguimentos
Alemanha
Acetato de Glatiramer/uso terapêutico
Seres Humanos
Interferon beta/uso terapêutico
Assistência de Longa Duração
Masculino
Meia-Idade
Mitoxantrona/uso terapêutico
Neuromielite Óptica/imunologia
Prognóstico
Recidiva
Sistema de Registros
Estudos Retrospectivos
Rituximab/uso terapêutico
Resultado do Tratamento
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE; MULTICENTER STUDY
[Nm] Nome de substância:
0 (AQP4 protein, human); 0 (Aquaporin 4); 0 (Autoantibodies); 4F4X42SYQ6 (Rituximab); 5M691HL4BO (Glatiramer Acetate); 77238-31-4 (Interferon-beta); BZ114NVM5P (Mitoxantrone); MRK240IY2L (Azathioprine)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:171114
[Lr] Data última revisão:
171114
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170603
[St] Status:MEDLINE
[do] DOI:10.1136/jnnp-2017-315603


  7 / 1180 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28569182
[Au] Autor:Ross CJ; Towfic F; Shankar J; Laifenfeld D; Thoma M; Davis M; Weiner B; Kusko R; Zeskind B; Knappertz V; Grossman I; Hayden MR
[Ad] Endereço:Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC, Canada.
[Ti] Título:A pharmacogenetic signature of high response to Copaxone in late-phase clinical-trial cohorts of multiple sclerosis.
[So] Source:Genome Med;9(1):50, 2017 May 31.
[Is] ISSN:1756-994X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Copaxone is an efficacious and safe therapy that has demonstrated clinical benefit for over two decades in patients with relapsing forms of multiple sclerosis (MS). On an individual level, patients show variability in their response to Copaxone, with some achieving significantly higher response levels. The involvement of genes (e.g., HLA-DRB1*1501) with high inter-individual variability in Copaxone's mechanism of action (MoA) suggests the potential contribution of genetics to treatment response. This study aimed to identify genetic variants associated with Copaxone response in patient cohorts from late-phase clinical trials. METHODS: Single nucleotide polymorphisms (SNPs) associated with high and low levels of response to Copaxone were identified using genome-wide SNP data in a discovery cohort of 580 patients from two phase III clinical trials of Copaxone. Multivariable Bayesian modeling on the resulting SNPs in an expanded discovery cohort with 1171 patients identified a multi-SNP signature of Copaxone response. This signature was examined in 941 Copaxone-treated MS patients from seven independent late-phase trials of Copaxone and assessed for specificity to Copaxone in 310 Avonex-treated and 311 placebo-treated patients, also from late-phase trials. RESULTS: A four-SNP signature consisting of rs80191572 (in UVRAG), rs28724893 (in HLA-DQB2), rs1789084 (in MBP), and rs139890339 (in ZAK(CDCA7)) was identified as significantly associated with Copaxone response. Copaxone-treated signature-positive patients had a greater reduction in annualized relapse rate (ARR) compared to signature-negative patients in both discovery and independent cohorts, an effect not observed in Avonex-treated patients. Additionally, signature-positive placebo-treated cohorts did not show a reduction in ARR, demonstrating the predictive as opposed to prognostic nature of the signature. A 10% subset of patients, delineated by the signature, showed marked improvements across multiple clinical parameters, including ARR, MRI measures, and higher proportion with no evidence of disease activity (NEDA). CONCLUSIONS: This study is the largest pharmacogenetic study in MS reported to date. Gene regions underlying the four-SNP signature have been linked with pathways associated with either Copaxone's MoA or the pathophysiology of MS. The pronounced association of the four-SNP signature with clinical improvements in a ~10% subset of the MS patient population demonstrates the complex interplay of immune mechanisms and the individualized nature of response to Copaxone.
[Mh] Termos MeSH primário: Acetato de Glatiramer/uso terapêutico
Esclerose Múltipla/tratamento farmacológico
Variantes Farmacogenômicos
Polimorfismo de Nucleotídeo Único
[Mh] Termos MeSH secundário: Adulto
Teorema de Bayes
Ensaios Clínicos Fase III como Assunto
Ensaios Clínicos Fase IV como Assunto
Feminino
Acetato de Glatiramer/genética
Seres Humanos
Masculino
Meia-Idade
Modelos Genéticos
Modelos Estatísticos
Esclerose Múltipla/genética
Medicina de Precisão
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
5M691HL4BO (Glatiramer Acetate)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170901
[Lr] Data última revisão:
170901
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170602
[St] Status:MEDLINE
[do] DOI:10.1186/s13073-017-0436-y


  8 / 1180 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28475587
[Au] Autor:Alsop J; Medin J; Cornelissen C; Vormfelde SV; Ziemssen T
[Ad] Endereço:Numerus Ltd, Wokingham, United Kingdom.
[Ti] Título:Two studies in one: A propensity-score-matched comparison of fingolimod versus interferons and glatiramer acetate using real-world data from the independent German studies, PANGAEA and PEARL.
[So] Source:PLoS One;12(5):e0173353, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: This study compared outcomes following fingolimod or BRACE treatments (beta-interferons/glatiramer acetate) in patients with active MS (≥ 1 relapse in the previous year) following previous BRACE treatment. METHODS AND FINDINGS: Patients with active MS who previously received BRACE were identified from German prospective, observational studies, PANGAEA and PEARL. A novel methodology was developed to compare outcomes between propensity-score-matched cohorts (3:1 ratio) from the independent single-arm studies. Patients in PANGAEA (n = 1287) experienced 48% fewer relapses per year than those in PEARL (n = 429; annualized relapse rate ratio: 0.52; p < 0.001). The risk of 3-month or 6-month confirmed disability progression (CDP) was reduced in PANGAEA versus PEARL (3-month: 37% reduction; hazard ratio [HR], 0.63; p < 0.001; 6-month: 47% reduction; HR, 0.53; p < 0.001). A higher proportion of patients in PANGAEA (n = 1234) than PEARL (n = 401) were free from relapses and 3-month (65.7% vs 38.7%; p < 0.001) or 6-month (68.2% vs 39.2%; p < 0.001) CDP. The probability of confirmed disability improvement was higher in PANGAEA (n = 1163) than PEARL (n = 372; 3-month: 175% increase; HR, 2.75; p < 0.001; 6-month: 126% increase; HR, 2.26; p < 0.001). Patients in PANGAEA (n = 149) were less likely than those in PEARL (n = 307) to have taken sick leave (proportion with 0 days off work: 62.4% vs 44.6%; p = 0.0005). For change in disease severity from baseline (assessed by clinicians using the Clinical Global Impressions scale; PANGAEA, n = 1207; PEARL, n = 427), a larger proportion of patients had subjective improvement and a smaller proportion had worsening status in PANGAEA than PEARL (improvement: 28.2% vs 15.2%; worsening: 16.4% vs 30.4%; p < 0.0001). CONCLUSIONS: Fingolimod appears to be more effective than BRACE in improving clinical and physician-/patient-reported outcomes in individuals with active MS.
[Mh] Termos MeSH primário: Cloridrato de Fingolimode/uso terapêutico
Acetato de Glatiramer/uso terapêutico
Interferons/uso terapêutico
Esclerose Múltipla/tratamento farmacológico
[Mh] Termos MeSH secundário: Adolescente
Adulto
Idoso
Idoso de 80 Anos ou mais
Estudos de Coortes
Progressão da Doença
Feminino
Alemanha
Seres Humanos
Masculino
Meia-Idade
Esclerose Múltipla/patologia
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
5M691HL4BO (Glatiramer Acetate); 9008-11-1 (Interferons); G926EC510T (Fingolimod Hydrochloride)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170915
[Lr] Data última revisão:
170915
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170506
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0173353


  9 / 1180 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
Texto completo
[PMID]:28440858
[Au] Autor:Filippini G; Del Giovane C; Clerico M; Beiki O; Mattoscio M; Piazza F; Fredrikson S; Tramacere I; Scalfari A; Salanti G
[Ad] Endereço:Scientific Direction, Fondazione IRCCS, Istituto Neurologico Carlo Besta, via Celoria, 11, Milan, Italy, 20133.
[Ti] Título:Treatment with disease-modifying drugs for people with a first clinical attack suggestive of multiple sclerosis.
[So] Source:Cochrane Database Syst Rev;4:CD012200, 2017 Apr 25.
[Is] ISSN:1469-493X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: The treatment of multiple sclerosis has changed over the last 20 years. The advent of disease-modifying drugs in the mid-1990s heralded a period of rapid progress in the understanding and management of multiple sclerosis. With the support of magnetic resonance imaging early diagnosis is possible, enabling treatment initiation at the time of the first clinical attack. As most of the disease-modifying drugs are associated with adverse events, patients and clinicians need to weigh the benefit and safety of the various early treatment options before taking informed decisions. OBJECTIVES: 1. to estimate the benefit and safety of disease-modifying drugs that have been evaluated in all studies (randomised or non-randomised) for the treatment of a first clinical attack suggestive of MS compared either with placebo or no treatment;2. to assess the relative efficacy and safety of disease-modifying drugs according to their benefit and safety;3. to estimate the benefit and safety of disease-modifying drugs that have been evaluated in all studies (randomised or non-randomised) for treatment started after a first attack ('early treatment') compared with treatment started after a second attack or at another later time point ('delayed treatment'). SEARCH METHODS: We searched the Cochrane Multiple Sclerosis and Rare Diseases of the CNS Group Trials Register, MEDLINE, Embase, CINAHL, LILACS, clinicaltrials.gov, the WHO trials registry, and US Food and Drug Administration (FDA) reports, and searched for unpublished studies (until December 2016). SELECTION CRITERIA: We included randomised and observational studies that evaluated one or more drugs as monotherapy in adult participants with a first clinical attack suggestive of MS. We considered evidence on alemtuzumab, azathioprine, cladribine, daclizumab, dimethyl fumarate, fingolimod, glatiramer acetate, immunoglobulins, interferon beta-1b, interferon beta-1a (Rebif®, Avonex®), laquinimod, mitoxantrone, natalizumab, ocrelizumab, pegylated interferon beta-1a, rituximab and teriflunomide. DATA COLLECTION AND ANALYSIS: Two teams of three authors each independently selected studies and extracted data. The primary outcomes were disability-worsening, relapses, occurrence of at least one serious adverse event (AE) and withdrawing from the study or discontinuing the drug because of AEs. Time to conversion to clinically definite MS (CDMS) defined by Poser diagnostic criteria, and probability to discontinue the treatment or dropout for any reason were recorded as secondary outcomes. We synthesized study data using random-effects meta-analyses and performed indirect comparisons between drugs. We calculated odds ratios (OR) and hazard ratios (HR) along with relative 95% confidence intervals (CI) for all outcomes. We estimated the absolute effects only for primary outcomes. We evaluated the credibility of the evidence using the GRADE system. MAIN RESULTS: We included 10 randomised trials, eight open-label extension studies (OLEs) and four cohort studies published between 2010 and 2016. The overall risk of bias was high and the reporting of AEs was scarce. The quality of the evidence associated with the results ranges from low to very low. Early treatment versus placebo during the first 24 months' follow-upThere was a small, non-significant advantage of early treatment compared with placebo in disability-worsening (6.4% fewer (13.9 fewer to 3 more) participants with disability-worsening with interferon beta-1a (Rebif®) or teriflunomide) and in relapses (10% fewer (20.3 fewer to 2.8 more) participants with relapses with teriflunomide). Early treatment was associated with 1.6% fewer participants with at least one serious AE (3 fewer to 0.2 more). Participants on early treatment were on average 4.6% times (0.3 fewer to 15.4 more) more likely to withdraw from the study due to AEs. This result was mostly driven by studies on interferon beta 1-b, glatiramer acetate and cladribine that were associated with significantly more withdrawals for AEs. Early treatment decreased the hazard of conversion to CDMS (HR 0.53, 95% CI 0.47 to 0.60). Comparing active interventions during the first 24 months' follow-upIndirect comparison of interferon beta-1a (Rebif®) with teriflunomide did not show any difference on reducing disability-worsening (OR 0.84, 95% CI 0.43 to 1.66). We found no differences between the included drugs with respect to the hazard of conversion to CDMS. Interferon beta-1a (Rebif®) and teriflunomide were associated with fewer dropouts because of AEs compared with interferon beta-1b, cladribine and glatiramer acetate (ORs range between 0.03 and 0.29, with substantial uncertainty). Early versus delayed treatmentWe did not find evidence of differences between early and delayed treatments for disability-worsening at a maximum of five years' follow-up (3% fewer participants with early treatment (15 fewer to 11.1 more)). There was important variability across interventions; early treatment with interferon beta-1b considerably reduced the odds of participants with disability-worsening during three and five years' follow-up (OR 0.52, 95% CI 0.32 to 0.84 and OR 0.57, 95% CI 0.36 to 0.89). The early treatment group had 19.6% fewer participants with relapses (26.7 fewer to 12.7 fewer) compared to late treatment at a maximum of five years' follow-up and early treatment decreased the hazard of conversion to CDMS at any follow-up up to 10 years (i.e. over five years' follow-up HR 0.62, 95% CI 0.53 to 0.73). We did not draw any conclusions on long-term serious AEs or discontinuation due to AEs because of inadequacies in the available data both in the included OLEs and cohort studies. AUTHORS' CONCLUSIONS: Very low-quality evidence suggests a small and uncertain benefit with early treatment compared with placebo in reducing disability-worsening and relapses. The advantage of early treatment compared with delayed on disability-worsening was heterogeneous depending on the actual drug used and based on very low-quality evidence. Low-quality evidence suggests that the chances of relapse are less with early treatment compared with delayed. Early treatment reduced the hazard of conversion to CDMS compared either with placebo, no treatment or delayed treatment, both in short- and long-term follow-up. Low-quality evidence suggests that early treatment is associated with fewer participants with at least one serious AE compared with placebo. Very low-quality evidence suggests that, compared with placebo, early treatment leads to more withdrawals or treatment discontinuation due to AEs. Difference between drugs on short-term benefit and safety was uncertain because few studies and only indirect comparisons were available. Long-term safety of early treatment is uncertain because of inadequately reported or unavailable data.
[Mh] Termos MeSH primário: Adjuvantes Imunológicos/uso terapêutico
Imunossupressores/uso terapêutico
Esclerose Múltipla/tratamento farmacológico
[Mh] Termos MeSH secundário: Adjuvantes Imunológicos/efeitos adversos
Cladribina/efeitos adversos
Cladribina/uso terapêutico
Estudos de Coortes
Crotonatos/efeitos adversos
Crotonatos/uso terapêutico
Progressão da Doença
Acetato de Glatiramer/efeitos adversos
Acetato de Glatiramer/uso terapêutico
Seres Humanos
Imunossupressores/efeitos adversos
Interferon beta-1a/efeitos adversos
Interferon beta-1a/uso terapêutico
Viés de Publicação
Ensaios Clínicos Controlados Aleatórios como Assunto
Recidiva
Fatores de Tempo
Toluidinas/efeitos adversos
Toluidinas/uso terapêutico
[Pt] Tipo de publicação:JOURNAL ARTICLE; META-ANALYSIS; REVIEW
[Nm] Nome de substância:
0 (Adjuvants, Immunologic); 0 (Crotonates); 0 (Immunosuppressive Agents); 0 (Toluidines); 1C058IKG3B (teriflunomide); 47M74X9YT5 (Cladribine); 5M691HL4BO (Glatiramer Acetate); XRO4566Q4R (Interferon beta-1a)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170802
[Lr] Data última revisão:
170802
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170426
[St] Status:MEDLINE
[do] DOI:10.1002/14651858.CD012200.pub2


  10 / 1180 MEDLINE  
              first record previous record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28328179
[Au] Autor:Havrdova E; Giovannoni G; Gold R; Fox RJ; Kappos L; Phillips JT; Okwuokenye M; Marantz JL
[Ad] Endereço:Department of Neurology, First Faculty of Medicine, Charles University, Prague, Czech Republic.
[Ti] Título:Effect of delayed-release dimethyl fumarate on no evidence of disease activity in relapsing-remitting multiple sclerosis: integrated analysis of the phase III DEFINE and CONFIRM studies.
[So] Source:Eur J Neurol;24(5):726-733, 2017 May.
[Is] ISSN:1468-1331
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND AND PURPOSE: Significant effects on clinical/neuroradiological disease activity have been reported in patients with relapsing-remitting multiple sclerosis treated with delayed-release dimethyl fumarate (DMF) in phase III DEFINE/CONFIRM trials. We conducted a post hoc analysis of integrated data from DEFINE/CONFIRM to evaluate the effect of DMF on achieving no evidence of disease activity (NEDA) in patients with relapsing-remitting multiple sclerosis. METHODS: The analysis included patients randomized to DMF 240 mg twice daily, placebo or glatiramer acetate (CONFIRM only) for ≤2 years. A time-to-event method was used to estimate the percentage of patients achieving NEDA. Clinical NEDA (no relapses/no 12-week confirmed disability progression) was analysed in the intention-to-treat (ITT) population. Neuroradiological (no new/newly enlarging T2 hyperintense lesions/no gadolinium-enhancing lesions) and overall NEDA (clinical and neuroradiological NEDA) were analysed in the magnetic resonance imaging (MRI) cohort. RESULTS: The ITT and MRI populations comprised 1540 and 692 patients, respectively. The percentage of patients with clinical NEDA (ITT population) and neuroradiological NEDA (MRI cohort) was higher with DMF versus placebo over 2 years [clinical NEDA: 38.9% relative reduction; hazard ratio (HR), 0.61; 95% confidence interval (CI), 0.52-0.72; P < 0.0001; neuroradiological NEDA: 40.0% relative reduction; HR, 0.60; 95% CI, 0.49-0.73; P < 0.0001]. The percentage of patients achieving overall NEDA (MRI cohort) was also higher with DMF (26%) versus placebo (12%) over 2 years, with a relative risk reduction of 42.7% (HR, 0.57; 95% CI, 0.48-0.69; P < 0.0001). CONCLUSIONS: A significantly higher percentage of patients treated with DMF achieved NEDA status over 2 years compared with placebo.
[Mh] Termos MeSH primário: Fumarato de Dimetilo/farmacologia
Progressão da Doença
Acetato de Glatiramer/farmacologia
Imunossupressores/farmacologia
Esclerose Múltipla Recidivante-Remitente/diagnóstico por imagem
Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico
[Mh] Termos MeSH secundário: Adulto
Preparações de Ação Retardada
Fumarato de Dimetilo/administração & dosagem
Feminino
Acetato de Glatiramer/administração & dosagem
Seres Humanos
Imunossupressores/administração & dosagem
Imagem por Ressonância Magnética/métodos
Masculino
Meia-Idade
Recidiva
Resultado do Tratamento
[Pt] Tipo de publicação:CLINICAL TRIAL, PHASE III; JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
0 (Delayed-Action Preparations); 0 (Immunosuppressive Agents); 5M691HL4BO (Glatiramer Acetate); FO2303MNI2 (Dimethyl Fumarate)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170605
[Lr] Data última revisão:
170605
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170323
[St] Status:MEDLINE
[do] DOI:10.1111/ene.13272



página 1 de 118 ir para página                         
   


Refinar a pesquisa
  Base de dados : MEDLINE Formulário avançado   

    Pesquisar no campo  
1  
2
3
 
           



Search engine: iAH v2.6 powered by WWWISIS

BIREME/OPAS/OMS - Centro Latino-Americano e do Caribe de Informação em Ciências da Saúde