RESUMO
OBJECTIVE: To examine patient and significant other characteristics as predictors of significant other well-being. METHODS: A total of 74 persons with multiple sclerosis (MS) and their significant others participated. Executive functioning was measured using neuropsychological tests. Awareness of cognitive deficit was measured as the discrepancy between the patient's reports of their abilities and objective test results. Awareness of functional deficit was measured as the discrepancy between the patient's and significant other's reports of the patient's functional abilities. Patient neurobehavioral disturbance was measured using a significant-other rated questionnaire. Significant other perceived social support and well-being (ie, psychological distress, life satisfaction, and general health status) were assessed using questionnaires filled out by the significant other. RESULTS: Executive dysfunction, neurobehavioral disturbance, and lack of awareness of functional deficits in patients were associated with poor well-being outcomes; whereas, lack of awareness of cognitive deficits was only weakly related to well-being. Social support was associated with positive well-being outcomes. CONCLUSIONS: Diminished insight regarding functional limitations may increase significant others' supervisory burden as patients attempt activities independently, whereas lack of awareness of cognitive deficits may not be directly associated with behavior-relevant impairments that significant others find distressing. Social support appears to be a powerful aid in diffusing the distress among significant others of MS patients.
Assuntos
Cuidadores/psicologia , Saúde da Família , Esclerose Múltipla/psicologia , Apoio Social , Adulto , Sintomas Afetivos , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Análise de Regressão , Índice de Gravidade de DoençaRESUMO
A decade of continuous glatiramer acetate (GA) use by relapsing remitting multiple sclerosis (RRMS) patients was evaluated in this ongoing, prospective study, and the neurological status of 'Withdrawn' patients was assessed at a 10-year long-term follow-up (LTFU) visit. Modified intention-to-treat (mITT, n=232) patients received > or =1 GA dose since 1991; 'Ongoing' patients (n = 108) continued in November 2003. Of 124 patients, 50 Withdrawn patients returned for LTFU. Patients were evaluated every six months (EDSS). Mean GA exposure was 6.99, 10.1 and 4.26 years for mITT, Ongoing, and Withdrawn/LTFU patients, respectively. While on GA, mITT relapse rates declined from 1.18/year prestudy to approximately 1 relapse/5 years; median time to > or = 1 EDSS point increase was 8.8 years; mean EDSS change was 0.73 +/- 1.66 points; 58% had stable/improved EDSS scores; and 24, 11 and 3% reached EDSS 4, 6 and 8, respectively. For Ongoing patients, EDSS increased 0.50 +/- 1.65; 62% were stable/improved; and 24,8 and 1% reached EDSS 4, 6 and 8, respectively. For Withdrawn patients at 10-year LTFU, EDSS increased 2.24 +/- 1.86; 28% were stable/improved; and 68, 50 and 10% reached EDSS 4, 6 and 8, respectively. While on GA nearly all patients (mean disease duration 15 years) remained ambulatory. At LTFU, Withdrawn patients had greater disability than Ongoing patients.
Assuntos
Imunossupressores/administração & dosagem , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Peptídeos/administração & dosagem , Adulto , Avaliação da Deficiência , Feminino , Seguimentos , Acetato de Glatiramer , Humanos , Fatores Imunológicos/administração & dosagem , Fatores Imunológicos/efeitos adversos , Imunossupressores/efeitos adversos , Masculino , Pessoa de Meia-Idade , Pacientes Desistentes do Tratamento , Peptídeos/efeitos adversos , Estudos Prospectivos , Fatores de Tempo , Resultado do TratamentoRESUMO
Cytokines secreted within the central nervous system (CNS) are important in the development of multiple sclerosis (MS) lesions. The balance between Th1, monocyte/macrophage (M/M) and Th2 cytokines in the CNS may be pivotal in determining the outcome of lesion development. We examined the effects of mixtures of cytokines on gene expression by CNS glial cells, as mixtures of cytokines are present in MS lesions, which in turn contain mixtures of glial cells. In this initial analysis by gene array, we examined changes at 6 hours to identify early changes in gene expression that represent primary responses to the cytokines. Rat glial cells were incubated with mixtures of Th1, M/M and Th2 cytokines for 6 hours and examined for changes in early gene expression employing microarray gene chip technology. A minimum of 814 genes were differentially regulated by one or more of the cytokine mixtures in comparison to controls, including changes in expression in a large number of genes for immune system-related proteins. Expression of the proteins for these genes likely influences development and inhibition of MS lesions as well as protective and regenerative processes. Analysing gene expression for the effects of various combinations of exogenous cytokines on glial cells in the absence of the confounding effects of inflammatory cells themselves should increase our understanding of cytokine-induced pathways in the CNS.
Assuntos
Citocinas/imunologia , Regulação da Expressão Gênica/imunologia , Macrófagos/imunologia , Neuroglia/imunologia , Células Th1/imunologia , Células Th2/imunologia , Animais , Sobrevivência Celular , Células Cultivadas , Antígenos de Histocompatibilidade Classe I/análise , Antígenos de Histocompatibilidade Classe I/genética , Antígenos de Histocompatibilidade Classe II/análise , Monócitos/imunologia , Neuroglia/citologia , Análise de Sequência com Séries de Oligonucleotídeos , RatosRESUMO
OBJECTIVE: To assess the long-term effectiveness of continuous glatiramer acetate (GA) therapy in relapsing-remitting multiple sclerosis (RRMS). METHODS: This open-label extension followed a randomized, placebo-controlled, double-blind study of GA of approximately 30 months duration. Patients originally randomized to GA continued on it (group A) and those randomized to placebo switched to GA (group B). RESULTS: Of 251 original patients, 142 (56.6%) remained in the study after 8 years. Annual relapse rate for both groups declined to approximately 0.2 (approximately one relapse every 5 years). However, a significantly larger proportion of patients in group A had stable or improved Expanded Disability Status Scale scores compared with group B (65.3% vs 50.4%, respectively; P = 0.0263), possibly attributable to the delay of GA treatment for approximately 30 months in group B. GA was well tolerated and no drug-related laboratory changes were observed. CONCLUSIONS: These data support early initiation of GA therapy as an efficacious and well-tolerated long-term treatment for RRMS patients.
Assuntos
Imunossupressores/administração & dosagem , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Peptídeos/administração & dosagem , Avaliação da Deficiência , Acetato de Glatiramer , Humanos , Imunossupressores/efeitos adversos , Peptídeos/efeitos adversos , Estudos Prospectivos , Recidiva , Fatores de Tempo , Resultado do TratamentoRESUMO
The aim of this study was to assess the long-term safety and efficacy of glatiramer acetate (GA) for patients with multiple sclerosis (MS) who received active treatment versus those on placebo for approximately 30 months (24-35 months) before receiving GA during a six-year organized, prospective open label study. Entry required two relapses in the previous two years and an Expanded Disability Status Scale (EDSS) score of 0-5. Patients (251) were equally randomized to daily subcutaneous GA, 20 mg, or to placebo. After approximately 30 months, 208 patients continued in an open label study: 101 continued on GA and 107 switched from placebo to active drug. Groups were well matched at randomization and entry to the open label study. Patients always on GA showed a steady decline in relapses: a mean of 1.5 per year at entry, a mean of 0.42 over the entire six years (95% CI = 0.34-0.51), a 72% reduction (P = 0.0001). They averaged a relapse every four + years (yearly rate 0.23 in year six) and 26/101 remain relapse free. Patients did less well if on placebo for 30 months, but relapses then declined, and by year six the rates were similar. Of patients always on GA, 69% showed neurological improvement of > or = 1 EDSS steps or remained stable compared with 57% if GA treatment was delayed. Of relapse-free patients always on GA over six years, only three of 26 (11%) were worse by > or = 1 EDSS steps, whereas nine of 21 (43%) in the placebo/active group were worse (P < 0.03). Disability, measured every six months, showed that the group of patients always on GA was relatively stable over the six years, while the group who received placebo for the first two-and-a-half years did significantly less well. Daily injections of GA were well tolerated. This longest ever organized MS treatment trial shows that delaying therapy with GA increases the risk of neurologic disability, reinforcing the rationale for using GA as a first-line treatment early in the course of relapsing-remitting MS.
Assuntos
Imunossupressores/administração & dosagem , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Peptídeos/administração & dosagem , Avaliação da Deficiência , Acetato de Glatiramer , Humanos , Imunossupressores/efeitos adversos , Imageamento por Ressonância Magnética , Esclerose Múltipla Recidivante-Remitente/patologia , Peptídeos/efeitos adversos , Estudos Prospectivos , Resultado do TratamentoRESUMO
Intercaudate nucleus ratio (ICR) is a linear measure of brain atrophy that does not require software application and is independent of image acquisition techniques. The authors examined the relationship between ICR and disability in 190 patients with MS. The results show that ICR correlates with Expanded Disability Status Scale score (r = 0.67; p = 0.0001) and disease duration (r = 0.32; p < 0.01). Intercaudate ratio appears to be a reliable and reproducible linear measure of brain atrophy and correlates with disability and disease duration in MS.
Assuntos
Atrofia/diagnóstico , Encéfalo/patologia , Esclerose Múltipla Crônica Progressiva/diagnóstico , Esclerose Múltipla Recidivante-Remitente/diagnóstico , Adulto , Atrofia/complicações , Núcleo Caudado/patologia , Estudos Transversais , Avaliação da Deficiência , Progressão da Doença , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla Crônica Progressiva/complicações , Esclerose Múltipla Recidivante-Remitente/complicações , Valor Preditivo dos Testes , Estudos Retrospectivos , Fatores SexuaisRESUMO
Schwann cells differentiate in vivo in response to contact with axons, and cAMP simulates some of these aspects of differentiation in vitro, particularly morphologic changes and expression of certain phenotypic molecules. Unfractionated inflammatory cytokines inhibit cAMP-induced Schwann cell expression of galactolipids (Gal). We sought to identify which cytokines were responsible for this inhibition and to determine whether other phenotypic indicators of Schwann cell differentiation were also affected. Neonatal rat Schwann cells were incubated in vitro with 1 mM 8 Bromo cAMP (8 Br cAMP) with or without the addition of interleukin-1 alpha (IL-1 alpha), IL-1 beta, IL-2, IL-6, tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), or transforming growth factor-beta (TGF-beta). Cells were then examined for morphologic changes and for expression of surface Gal and low-affinity nerve growth factor receptor (NGFRp75), employing indirect immunofluorescence. 8 Br cAMP induced Schwann cell upregulation of Gal, downregulation of NGFRp75, and the cells became enlarged and somewhat amorphous and irregular in appearance. Cells treated with IFN-gamma or TNF-alpha alone were more bipolar and more evenly distributed on coverslips than were control cells, whereas TGF-beta alone induced elongated cells often in a swirling pattern. None of the cytokines alone induced upregulation of Gal or downregulation of NGFRp75. TNF-alpha, IFN-gamma, and TGF-beta inhibited the 8 Br cAMP-induced morphologic changes, as well as the upregulation of Gal and downregulation of NGFRp75. The other cytokines had no effects on Gal or NGFRp75 expression. Thus, these three cytokines, which are present in inflammatory lesions in the peripheral nervous system, are capable of inhibiting Schwann cell differentiation.
Assuntos
Diferenciação Celular/imunologia , Citocinas/imunologia , Doenças Desmielinizantes/imunologia , Inflamação/imunologia , Sistema Nervoso Periférico/imunologia , Células de Schwann/imunologia , 8-Bromo Monofosfato de Adenosina Cíclica/farmacologia , Animais , Animais Recém-Nascidos , Diferenciação Celular/efeitos dos fármacos , Células Cultivadas , AMP Cíclico/antagonistas & inibidores , AMP Cíclico/metabolismo , Citocinas/antagonistas & inibidores , Citocinas/metabolismo , Doenças Desmielinizantes/patologia , Doenças Desmielinizantes/fisiopatologia , Relação Dose-Resposta a Droga , Regulação para Baixo/efeitos dos fármacos , Regulação para Baixo/fisiologia , Galactolipídeos , Glicolipídeos/agonistas , Glicolipídeos/metabolismo , Inflamação/patologia , Inflamação/fisiopatologia , Interferon gama/antagonistas & inibidores , Interferon gama/imunologia , Interferon gama/metabolismo , Sistema Nervoso Periférico/patologia , Sistema Nervoso Periférico/fisiopatologia , Ratos , Ratos Sprague-Dawley , Receptor de Fator de Crescimento Neural/antagonistas & inibidores , Receptor de Fator de Crescimento Neural/metabolismo , Células de Schwann/efeitos dos fármacos , Células de Schwann/metabolismo , Fator de Crescimento Transformador beta/antagonistas & inibidores , Fator de Crescimento Transformador beta/imunologia , Fator de Crescimento Transformador beta/metabolismo , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Fator de Necrose Tumoral alfa/imunologia , Fator de Necrose Tumoral alfa/metabolismo , Regulação para Cima/efeitos dos fármacos , Regulação para Cima/fisiologiaRESUMO
Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system in which peripheral blood monocytes play an important role. We have previously reported that patients with chronic progressive MS (CPMS) have significantly increased numbers of circulating monocytes which express the urokinase plasminogen activator receptor (uPAR). In the present study, we examined the expression of uPAR on monocytes in patients with relapsing-remitting multiple sclerosis (RRMS) not currently participating in a clinical trial and in patients with RRMS who were enrolled in a double-blind multicenter clinical trial designed to examine the effect of glatiramer acetate (copolymer 1; Copaxone) on relapsing disease. Patients with CPMS have sustained high levels of circulating uPAR-positive (uPAR(+)) monocytes. In comparison, patients with RRMS displayed variable levels of circulating uPAR(+) monocytes. Mean values for uPAR in patients with RRMS were above those seen for controls but were not as high as those observed for patients with secondary progressive MS. Patients with RRMS in the clinical trial also had variable levels of monocyte uPAR. However, patients in the treatment group displayed lower levels following 2 years of treatment. In both placebo-treated and glatiramer acetate-treated patients, the percentage of circulating uPAR(+) monocytes, as well as the density of uPAR expressed per cell (mean linear fluorescence intensity), increased just prior to the onset of a clinically documented exacerbation. Values fell dramatically with the development of clinical symptoms. uPAR levels in all groups correlated with both clinical activity and severity. Results indicate that monocyte activation is impatient in MS and that glatiramer acetate may have a significant effect on monocyte activation in patients with RRMS.
Assuntos
Imunossupressores/uso terapêutico , Monócitos/metabolismo , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Esclerose Múltipla Recidivante-Remitente/imunologia , Peptídeos/uso terapêutico , Receptores de Superfície Celular/biossíntese , Anticorpos Monoclonais , Avaliação da Deficiência , Método Duplo-Cego , Feminino , Citometria de Fluxo , Acetato de Glatiramer , Humanos , Estudos Longitudinais , Masculino , Monócitos/química , Monócitos/imunologia , Esclerose Múltipla Crônica Progressiva/tratamento farmacológico , Esclerose Múltipla Crônica Progressiva/imunologia , Receptores de Superfície Celular/análise , Receptores de Superfície Celular/imunologia , Receptores de Ativador de Plasminogênio Tipo UroquinaseRESUMO
Intravenous gamma globulin (IVIg) is used in the treatment of immunologic diseases that affect the entire neuroaxis, including the brain, spinal cord, peripheral nerves, muscles, and neuromuscular junction. The panel reviewed the available literature on the use of IVIg in order to evaluate the efficacy of this therapy in neuroimmunologic diseases. In prospective, rigorously controlled, double-blinded clinical trials, IVIg was found to have proven efficacy in the Guillain-Barré syndrome, chronic inflammatory demyelinating polyneuropathy, multifocal motor neuropathy, dermatomyositis, and Lambert-Eaton myasthenic syndrome. It was found to be probably effective in myasthenia gravis and polymyositis, and possibly effective in several other neuroimmunologic diseases. Further studies are needed to evaluate the use of IVIg for neuroimmunologic diseases in which its efficacy is suspected but not proven and to elucidate its mechanisms of action.
Assuntos
Doenças do Sistema Imunitário/terapia , Imunoglobulinas Intravenosas/uso terapêutico , Doenças do Sistema Nervoso/terapia , Ensaios Clínicos como Assunto , HumanosRESUMO
Fourteen consecutive clinically definite relapsing-remitting multiple sclerosis (MS) patients were treated with monthly intravenous cyclophosphomide (CTX) for 6 months. All had experienced severe dinical deterioration during the 12 months prior to treatment with CTX despite treatment with conventional immunomodulating agents and intravenous methylprednisolone. Treatment with CTX led to improvement and neurologic stability within 6 months which was sustained for at least 18 months after the onset of treatment with CTX. Therapy with CTX was well tolerated. CTX may be of benefit in MS patients who experience rapid clinical worsening and are resistant to conventional therapy.
Assuntos
Ciclofosfamida/administração & dosagem , Imunossupressores/administração & dosagem , Esclerose Múltipla/tratamento farmacológico , Adulto , Feminino , Humanos , Injeções Intravenosas , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
Self acetylcholine receptor (AchR) is targeted by a wayward immune response in myasthenia gravis (MG). The current understanding of the pathogenesis of the AChR-directed immune response is reviewed. Furthermore, the thymus is suspected of initiating and perpetuating the disease process in the majority of patients; its role as a central and peripheral lymphoid organ in MG is discussed. MG seems to result from a failure of (1) establishing tolerance to the AChR and (2) regulating the immune response.
Assuntos
Miastenia Gravis/imunologia , Timo , Autoantígenos/imunologia , Linfócitos B/imunologia , Humanos , Receptores Colinérgicos/imunologia , Linfócitos T/imunologia , Timo/citologia , Timo/imunologiaRESUMO
A prospective, non-randomized, open-label treatment trial was performed in patients with relapsing-remitting multiple sclerosis (RRMS), with follow up for 12 months. Our primary objective was to prospectively compare the effect of IFNbeta-1a (Avonex), IFNbeta-1b (Betaseron), and glatiramer acetate (GA, Copaxone) on the relapse rate in patients with RRMS. Between August 1996 and September 1999, 156 consecutive patients with clinically definite RRMS with a Kurtzke scale (EDSS) score of 4 or less were followed for 12 months, from the time of initiating therapy or electing to remain untreated. Prior 2-year relapse history and available chart information was carefully reviewed at the time of enrolment. Thirty-three of 156 elected no treatment (mean age 32.5 years; mean EDSS 2.64) at enrolment; 40 elected IFNbeta-1a (mean age 32.4 years; mean EDSS 2.69), 41 IFNbeta-1b (mean age 32.1 years; mean EDSS 2.56), and 42 chose GA (mean age 31.5 years; mean EDSS 2.57). Annual relapse rate based upon the 2 years prior to enrolment was 1.08 in the untreated group, 1.20 in the AV group, 1.21 in the BE group, and 1.10 in the GA group. There were no statistically significant differences among the four groups at enrolment. After 12 months of treatment, patients in the untreated groups had a relapse rate of 0.97, whereas patients in the IFNbeta-1a, IFNbeta-1b, and GA groups had relapse rate of 0.85, 0.61, and 0.62, respectively. Compared to the untreated group, reduction in the relapse rate was statistically significant only in the GA (P=0.003) and IFNbeta-1b (P=0.002) groups, in contrast to the IFNbeta-1a treated patients, who did not show a significant reduction (P=0.309). Compared to the untreated patients, mean EDSS was significantly reduced only in the GA (P=0.001) and IFNbeta-1b (P=0.01), in contrast to IFNbeta-1a treated patients (P=0.51). In this prospective, controlled, open-label, non-randomized 12-month study, treatment with only GA and IFNbeta-1b significantly reduced the relapse rate compared to untreated patients, supporting early treatment in RRMS. Our results are similar to the observations made after 12 months of therapy in phase III studies of IFNbeta-1a, IFNbeta-1b, and GA. Despite some limitations of the study design, the results provide helpful clinical information regarding the relative efficacy of each therapy in mildly affected treatment-naïve RRMS patients.
Assuntos
Adjuvantes Imunológicos/uso terapêutico , Interferon beta/uso terapêutico , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Peptídeos/uso terapêutico , Adulto , Feminino , Acetato de Glatiramer , Humanos , Interferon beta-1a , Interferon beta-1b , Masculino , Esclerose Múltipla Recidivante-Remitente/fisiopatologia , Estudos Prospectivos , Recidiva , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
We reported Schwann cell (SC)-specific autoregulation of IL-1 in vitro [J. Neuroimmunol. 74 (1997a)]. Whether SC resume this autoregulatory potential in vivo and what significance it may have for processes leading to inflammation and demyelination of the peripheral nerve remain obscure. Therefore, we examine SC-specific autoregulation of IL-1alpha, IL-1beta and their natural antagonist IL-1 receptor antagonist (IL-1Ra) during experimental autoimmune neuritis (EAN), a model for the human Guillain-Barre syndrome. Autoregulation of IL-1 by SC was analyzed in both, actively induced and adoptively transferred, EAN. Sciatic nerves were sampled before the onset of clinical signs, 2 to 11 days post immunization (dpi), with P2 peptide, and during clinically manifest disease, 11 to 15 dpi. In adoptively transferred EAN, sciatic nerves were analyzed at preclinical stage, 2 to 4 days post P2 peptide-specific cell transfer (dpt) and during clinical manifested phase, 5 to 10 dpt. In both models, IL-1alpha and IL-1beta were expressed by SC, during preclinical EAN. IL-1Ra was not detectable in SC at preclinical stage. Further development and progression to clinically manifest disease was accompanied by SC-specific expression of IL-1Ra. Although present in other cells in the nerve, IL-1alpha and IL-1beta were hardly detectable in SC during clinical EAN. IL-1Ra immunoreactivity highly co-localized with myelin associated glycoprotein (MAG), one of the markers for paranodal regions, sites essential for proper impulse transmission. Paranodes are also primary sites where activated macrophages make contact with SC, prior to infiltration.SC-specific autoregulation of IL-1 and IL-1Ra is suggestive of its relevance for immune regulation at paranodes during EAN.
Assuntos
Doenças Autoimunes/metabolismo , Interleucina-1/metabolismo , Neurite (Inflamação)/metabolismo , Células de Schwann/fisiologia , Sialoglicoproteínas/metabolismo , Animais , Doenças Autoimunes/imunologia , Expressão Gênica/fisiologia , Sistema Imunitário/fisiopatologia , Proteína Antagonista do Receptor de Interleucina 1 , Interleucina-1/genética , Linfonodos/fisiopatologia , Neurite (Inflamação)/imunologia , Ratos , Ratos Endogâmicos Lew , Sialoglicoproteínas/genéticaRESUMO
We previously reported results of a 12 month prospective, non-randomized, open-label treatment trial of immunomodulatory therapy in patients with relapsing-remitting multiple sclerosis (RRMS). We now report the results after 18 months of follow-up. Our primary objective was to compare the effect of IFNbeta-1a (Avonex), IFNbeta-1b (Betaseron), and Glatiramer Acetate (GA, Copaxone) to no treatment on the relapse rate in patients with RRMS. One hundred and fifty-six consecutive patients with clinically definite RRMS with a Kurtzke scale (EDSS) score of 4 or less were followed for 18 months. Prior 2-year relapse history and available chart information was carefully reviewed at the time of enrollment Thirty-three of 156 elected no treatment at enrollment; 40 elected IFNbeta-1a, 41 IFNbeta-1b, and 42 chose GA. There were no statistically significant differences among the four groups at enrollment. After 18 months of treatment 122 patients remained in their original treatment group. Compared to the untreated group (1.02), mean annualized number of relapses was significantly reduced only in the GA (0.49, P>0.0001) and IFNbeta-1b groups (0.55, P=0.001) in contrast to the IFNbeta-1a treated patients (0.81, P=0.106) who did not show a significant reduction. Despite limitations of the study design, the results provide helpful clinical information regarding the relative efficacy of each therapy in mildly affected treatment naive RRMS patients.
Assuntos
Adjuvantes Imunológicos/uso terapêutico , Imunossupressores/uso terapêutico , Interferon beta/uso terapêutico , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Peptídeos/uso terapêutico , Adulto , Avaliação da Deficiência , Feminino , Acetato de Glatiramer , Humanos , Interferon beta-1a , Interferon beta-1b , Masculino , Esclerose Múltipla Recidivante-Remitente/fisiopatologia , Estudos Prospectivos , Prevenção Secundária , Fatores de TempoAssuntos
Esclerose Múltipla Recidivante-Remitente/história , Peptídeos/história , Ensaios Clínicos Fase III como Assunto/história , Avaliação da Deficiência , Feminino , Acetato de Glatiramer , História do Século XX , Humanos , Masculino , Estudos Multicêntricos como Assunto/história , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Peptídeos/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto/históriaAssuntos
Adjuvantes Imunológicos/história , Esclerose Múltipla Recidivante-Remitente/história , Peptídeos/história , Adjuvantes Imunológicos/uso terapêutico , Avaliação da Deficiência , Acetato de Glatiramer , História do Século XX , Humanos , Injeções Subcutâneas , Assistência de Longa Duração , Esclerose Múltipla Recidivante-Remitente/terapia , Peptídeos/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto/históriaRESUMO
In a randomized, placebo-controlled, double-blind study, glatiramer acetate (Copaxone) reduced the relapse rate and slowed accumulation of disability for patients with relapsing - remitting multiple sclerosis. Of the original 251 patients randomized to receive glatiramer acetate or placebo, 208 chose to continue in an open-label study with all patients receiving active drug. The majority of the original double-blind cohort continues to receive glatiramer acetate by daily subcutaneous injection and are evaluated at 6-month intervals and during suspected relapse. The data reported here are from approximately 6 years of organized evaluation, including the double-blind phase of up to 35 months and the open-label phase of over 36 months. Daily subcutaneous injections of 20 mg glatiramer acetate were well tolerated. The mean annual relapse rate of the patients who received glatiramer acetate since randomization and continued into the open-label study was 0.42 (95% confidence interval (CI), CI=0.34 - 0.51). The rate per year has continued to drop and for the sixth year is 0.23. Of the group who have received glatiramer acetate without interruption for 5 or more years, 69.3% were neurologically unchanged or have improved from baseline by at least one step on the Expanded Disability Status Scale (EDSS). Patients who left the open-label phase were surveyed by questionnaire. The majority responded, providing information about their current status and reasons for dropping out. This study demonstrates the sustained efficacy of glatiramer acetate in reducing the relapse rate and in slowing the accumulation of disability in patients with relapsing forms of multiple sclerosis. Multiple Sclerosis (2000) 6 255 - 266
Assuntos
Adjuvantes Imunológicos/uso terapêutico , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Peptídeos/uso terapêutico , Adjuvantes Imunológicos/efeitos adversos , Adulto , Estudos de Coortes , Pessoas com Deficiência , Método Duplo-Cego , Feminino , Acetato de Glatiramer , Humanos , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla Recidivante-Remitente/fisiopatologia , Sistema Nervoso/fisiopatologia , Pacientes Desistentes do Tratamento , Peptídeos/efeitos adversos , Fatores de TempoAssuntos
Interferon Tipo I/efeitos adversos , Interferon Tipo I/imunologia , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica , Humanos , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/tratamento farmacológico , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/etiologia , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/imunologiaRESUMO
Several studies have suggested a possible association of human herpesvirus-6 (HHV-6) with multiple sclerosis (MS), a demyelinating disease with a variable course and progression. To determine whether HHV-6 could be detected in the sera of CSF of patients with different subtypes of MS, we performed nested polymerase chain reaction (PCR) on samples obtained from MS patients as well as samples from normal adults or individuals with other neurological diseases. Ninety-six serum samples from 24 patients with MS, including 13 individuals with relapsing remitting MS, one individual with primary progressive MS, seven individuals with secondary progressive MS and three individuals with an unspecified type were analyzed. Multiple serum samples were examined from individuals over varying periods of time and included samples obtained during exacerbations, remissions, and at different stages of progressive disease. HHV-6 DNA was detected only in one out of 15 serum samples that were collected over a number of years from one individual with secondary progressive MS. No HHV-6 DNA was detected in CSF from six patients with MS or 14 patients with other neurologic disease. These results indicate that the presence of HHV-6 DNA in the serum or CSF of patients with MS is not a common phenomenon, at least within the limits of the sensitivity of our assay.