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1.
Neurology ; 96(5): e783-e797, 2021 02 02.
Artículo en Inglés | MEDLINE | ID: mdl-33372028

RESUMEN

OBJECTIVE: To test the hypothesis that immunotherapy prevents long-term disability in relapsing-remitting multiple sclerosis (MS), we modeled disability outcomes in 14,717 patients. METHODS: We studied patients from MSBase followed for ≥1 year, with ≥3 visits, ≥1 visit per year, and exposed to MS therapy, and a subset of patients with ≥15-year follow-up. Marginal structural models were used to compare the cumulative hazards of 12-month confirmed increase and decrease in disability, Expanded Disability Status Scale (EDSS) step 6, and the incidence of relapses between treated and untreated periods. Marginal structural models were continuously readjusted for patient age, sex, pregnancy, date, disease course, time from first symptom, prior relapse history, disability, and MRI activity. RESULTS: A total of 14,717 patients were studied. During the treated periods, patients were less likely to experience relapses (hazard ratio 0.60, 95% confidence interval [CI] 0.43-0.82, p = 0.0016), worsening of disability (0.56, 0.38-0.82, p = 0.0026), and progress to EDSS step 6 (0.33, 0.19-0.59, p = 0.00019). Among 1,085 patients with ≥15-year follow-up, the treated patients were less likely to experience relapses (0.59, 0.50-0.70, p = 10-9) and worsening of disability (0.81, 0.67-0.99, p = 0.043). CONCLUSION: Continued treatment with MS immunotherapies reduces disability accrual by 19%-44% (95% CI 1%-62%), the risk of need of a walking aid by 67% (95% CI 41%-81%), and the frequency of relapses by 40-41% (95% CI 18%-57%) over 15 years. This study provides evidence that disease-modifying therapies are effective in improving disability outcomes in relapsing-remitting MS over the long term. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that, for patients with relapsing-remitting MS, long-term exposure to immunotherapy prevents neurologic disability.


Asunto(s)
Factores Inmunológicos/uso terapéutico , Esclerosis Múltiple Recurrente-Remitente/tratamiento farmacológico , Adulto , Evaluación de la Discapacidad , Progresión de la Enfermedad , Femenino , Clorhidrato de Fingolimod/uso terapéutico , Acetato de Glatiramer/uso terapéutico , Humanos , Inmunosupresores/uso terapéutico , Interferón beta/uso terapéutico , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Esclerosis Múltiple Recurrente-Remitente/fisiopatología , Natalizumab/uso terapéutico , Modelos de Riesgos Proporcionales
2.
BMC Infect Dis ; 20(1): 753, 2020 Oct 14.
Artículo en Inglés | MEDLINE | ID: mdl-33054715

RESUMEN

BACKGROUND: Safety of live vaccines in patients treated with immunosuppressive therapies is not well known, resulting in contradictory vaccination recommendations. We describe here the first case of vaccine-associated measles in a patient on natalizumab treatment. CASE PRESENTATION: A young female patient with relapsing-remitting multiple sclerosis on natalizumab treatment received the live attenuated measles, mumps, and rubella vaccine in preparation for a change in her treatment in favour of fingolimod, with established immunosuppressive qualities. Seven days after receiving the vaccine, our patient experienced diffuse muscle pain, fatigue, and thereafter developed a fever and then an erythematous maculopapular rash, compatible with vaccine associated measles. This was later confirmed by a positive measles RT-PCR throat swab. The patient's symptoms resolved without any sequelae. CONCLUSION: In this case report we review the immunosuppressive qualities of natalizumab and the evidence in favour and against live vaccines in patients on this treatment. Our findings reveal the insufficient understanding of the immunosuppressive effects of new immunomodulators, and thus of the safety of live vaccines in patients on such medications. While this case triggers precaution, there is insufficient evidence to conclude that natalizumab treatment could favor the onset of vaccine-associated measles.


Asunto(s)
Vacuna Antisarampión/efectos adversos , Vacuna contra el Sarampión-Parotiditis-Rubéola/uso terapéutico , Sarampión/etiología , Natalizumab/uso terapéutico , Adulto , Exantema/inducido químicamente , Femenino , Fiebre/etiología , Humanos , Factores Inmunológicos/uso terapéutico , Inmunosupresión/efectos adversos , Inmunosupresores/efectos adversos , Inmunosupresores/uso terapéutico , Sarampión/diagnóstico , Vacuna Antisarampión/uso terapéutico , Vacuna contra el Sarampión-Parotiditis-Rubéola/efectos adversos , Esclerosis Múltiple Recurrente-Remitente/tratamiento farmacológico , Natalizumab/inmunología , Vacunas Atenuadas/efectos adversos , Vacunas Atenuadas/inmunología , Vacunas Atenuadas/uso terapéutico
3.
Brasília; CONITEC; out. 2020.
No convencional en Portugués | BRISA/RedTESA | ID: biblio-1141598

RESUMEN

INTRODUÇÃO: A Esclerose Múltipla (EM) é uma doença imunomodulada, inflamatória, desmielinizante e neurodegenerativa, que acomete usualmente adultos jovens, sendo em média duas vezes mais frequente em mulheres. A prevalência média de EM estimada para o Brasil é de 8,69/100.000 habitantes. A evolução da doença, gravidade e sintomas não são uniformes, podendo apresentar-se de formas menos ativas até formas de evolução extremamente agressivas. A EM pode ser classificada em três formas, de acordo com a evolução da incapacidade e incidência de surtos. No Brasil, o tratamento farmacológico destina-se apenas a indivíduos que apresentam a EMRR, havendo seis medicamentos disponíveis em quatro linhas de tratamento, com o natalizumabe recomendado como opção da quarta linha terapêutica. PERGUNTA: O uso do natalizumabe é eficaz e seguro no tratamento da EMRR, após primeira falha ao tratamento, quando comparado ao fingolimode? EVIDÊNCIAS CIENTÍFICAS: Foram incluídas três revisões sistemáticas (RS) com meta-análise em rede avaliando a eficácia e a segurança de diversos Medicamentos Modificadores do Curso da Doença (MMCD) no tratamento da EMRR, além de 21 estudos observacionais comparando a efetividade do natalizumabe frente ao fingolimode. Com relação aos desfechos primários de eficácia, foi possível observar que houve diferença estatisticamente significante na taxa anualizada de surtos, com o resultado favorecendo o natalizumabe em uma das RS incluídas (Lucchetta et al, 2018). Já em relação ao desfecho de incidência de surtos, avaliado em 12 e 24 meses, não houve diferença entre os tratamentos aos 12 meses (Tramacere et al, 2015); e aos 24 meses foram obtidos resultados conflitantes com o estudo de Tramacere e colaboradores (2015) favorecendo o natalizumabe, ao contrário de Li et al. (2019), que não encontrou diferença entre as intervenções. Em termos de efetividade, foram realizadas 17 meta-análises, a partir dos 21 estudos observacionais incluídos. Dentre os desfechos primários avaliados, foi identificada superioridade do natalizumabe, com significância estatística, apenas para o desfecho de ausência de surto em 12 meses, inclusive na análise de subgrupos (indivíduos com alta atividade ou não). Entretanto, esse benefício parece não se manter para todos os pacientes a longo prazo, uma vez que aos 24 meses a meta-análise evidenciou um efeito protetor do natalizumabe apenas para indivíduos com alta atividade da EMRR. Os outros desfechos secundários de efetividade que demonstraram superioridade do natalizumabe foram expressos somente em pacientes com alta atividade da doença, não sendo possível, portanto, inferir que o tratamento com o natalizumabe deva se estender, nas mesmas proporções, a todos os pacientes com EMRR. Em relação à segurança, a maioria dos estudos avaliaram apenas o desfecho de descontinuação do tratamento, sempre em tempo menor do que 24 meses. Sabe-se, entretanto, que a segurança é um aspecto muito importante a ser considerado durante o uso de natalizumabe, principalmente com relação ao desenvolvimento de Leucoencefalopatia Multifocal Progressiva (LEMP) após dois anos de uso do natalizumabe. Dessa forma, destacamos resultados identificados na busca e que podem esclarecer essa lacuna, como o estudo de Oshima e colaboradores (2019) que demonstrou que o natalizumabe [OR 115,72 (IC95% 83,83-159,74) p<0,001]. apresenta uma chance estatisticamente significante maior que o fingolimode [OR 4,98 (IC95% 3,64-6,81)] para a incidência de LEMP. AVALIAÇÃO ECONÔMICA: O demandante apresentou uma análise de custo-efetividade utilizando um modelo de Markov em um horizonte temporal de 50 anos. O desfecho de efetividade considerado no modelo foi anos de vida ajustados pela qualidade (QALY) e os desfechos econômicos foram os custos com recursos médicos diretos. Os inputs utilizados foram extraídos de estudos publicados ou não, replicando as mesmas probabilidades de transição ao longo de todo o horizonte temporal. A avaliação resultou em um cenário de maior custo e maior efetividade para o natalizumabe, quando comparado ao fingolimode, gerando uma razão de custo-efetividade incremental de aproximadamente R$ 29 mil por QALY ganho. ANÁLISE DE IMPACTO ORÇAMENTÁRIO: O demandante apresentou uma Análise de Impacto Orçamentário (AIO) para estimar o impacto financeiro da antecipação do natalizumabe para após primeira falha terapêutica, em um horizonte temporal de 5 anos. A estimativa da população elegível foi realizada utilizando dados obtidos na base de dados do Sistema de Informações Ambulatoriais do SUS (SIA/SUS), acrescida de uma taxa anual de crescimento de pacientes observada de janeiro de 2017 a dezembro de 2018 (4,6%) para projetar a população ao longo do horizonte temporal de cinco anos. Adicionalmente, frente às evidências encontradas, estimou-se a população com EMRR em alta atividade que poderia se beneficiar com o uso de natalizumabe após a primeira falha terapêutica, além da descontinuação do tratamento para 57% dos pacientes após dois anos de uso do medicamento, referente à proporção de pessoas que apresentam anticorpos antiJCV (John Cunningham Virus). Assim, assumindo a antecipação do natalizumabe para pacientes com alta atividade da doença, estima-se um impacto orçamentário de R$ 4,86 milhões no primeiro ano, podendo chegar a R$ 7,14 milhões no quinto ano, representando um custo incremental total em cinco anos de R$ 32,4 milhões. MONITORAMENTO DO HORIZONTE TECNOLÓGICO: Na pesquisa realizada, foram detectados seis medicamentos potenciais para pacientes com esclerose múltipla remitente recorrente após primeira falha de tratamento, sendo que nenhum, até o momento, tem registro na Anvisa, nos Estados Unidos ou na Europa. CONSIDERAÇÕES FINAIS: As evidências apresentadas demonstraram os benefícios do tratamento com natalizumabe, principalmente em pacientes com alta atividade da EMRR. Entretanto, os resultados encontrados para pacientes sem essa definição de alta atividade foram similares aos obtidos com o comparador (fingolimode). Dado o perfil de segurança do natalizumabe e os achados de eficácia e efetividade, é possível que o uso deste medicamento supere os riscos somente em pacientes com alta atividade da EMRR, uma vez que estes apresentam pior prognóstico de progressão da doença. RECOMENDAÇÃO PRELIMINAR DA CONITEC: A Conitec, em sua 88ª reunião ordinária, no dia 09 de julho de 2020, recomendou a não ampliação de uso no SUS de natalizumabe para o tratamento da EMRR após primeira falha terapêutica, como alternativa ao fingolimode. A recomendação considerou que se indica haver evidência de superioridade do natalizumabe somente para pacientes em alta atividade da doença (no desfecho ausência de surto após 24 meses de tratamento). Contudo, atualmente, o PCDT não prevê essa classificação. Além disso, considerou-se o impacto orçamentário incremental de 32 milhões em 5 anos e as questões de segurança relativas ao risco de LEMP com natalizumabe. CONSULTA PÚBLICA: Foram recebidas 706 contribuições na Consulta Pública, sendo 87 pelo formulário para contribuições técnico-científicas e 619 pelo formulário para contribuições sobre experiência ou opinião de pacientes, familiares, amigos ou cuidadores de pacientes, profissionais de saúde ou pessoas interessadas no tema. Após apreciação das contribuições recebidas, em que foram reforçados os benefícios clínicos da utilização antecipada de natalizumabe para o tratamento de pacientes com alta atividade de doença; e considerando a nova proposta de atualização do PCDT da Esclerose Múltipla, que leva em conta essa classificação da EMRR, o Plenário da Conitec entendeu que houve argumentação suficiente para alterar a recomendação inicial sobre o tema. RECOMENDAÇÃO FINAL DA CONITEC: A Conitec, em sua 91ª reunião ordinária, no dia 08 de outubro de 2020, recomendou a ampliação de uso do natalizumabe no tratamento de pacientes com esclerose múltipla remitente-recorrente com alta atividade de doença, conforme estabelecido pelo Ministério da Saúde. A recomendação considerou que se indica haver evidência de superioridade do natalizumabe para pacientes com alta atividade da doença; e que a atual proposta de atualização do PCDT da esclerose múltipla aborda essa classificação da doença. DECISÃO: Ampliar o uso do natalizumabe no tratamento de pacientes com esclerose múltipla remitente-recorrente com alta atividade de doença, conforme estabelecido pelo Ministério da Saúde, no âmbito do Sistema Único de Saúde ­ SUS, conforme Portaria nº 49, publicada no Diário Oficial da União nº 217, seção 1, página 144, em 13 de novembro de 2020.


Asunto(s)
Humanos , Esclerosis Múltiple Recurrente-Remitente/tratamiento farmacológico , Natalizumab/uso terapéutico , Evaluación de la Tecnología Biomédica , Sistema Único de Salud , Brasil , Análisis Costo-Beneficio/economía , Insuficiencia del Tratamiento
5.
Neurology ; 95(6): e745-e754, 2020 08 11.
Artículo en Inglés | MEDLINE | ID: mdl-32690785

RESUMEN

OBJECTIVE: To determine whether natalizumab efficacy is maintained when switching to personalized extended interval dosing based on individual natalizumab trough concentrations in patients with relapsing-remitting multiple sclerosis (RRMS). METHODS: This was a prospective multicenter single-arm trial with 1 year follow-up and a 1-year extension phase. Participants were adult persons with RRMS treated with natalizumab without disease activity in the year prior to enrollment. The natalizumab treatment interval was based on longitudinal natalizumab trough concentrations. Patients received 3 monthly MRI scans, relapse assessments, and disability scoring during follow-up. The primary endpoint was the occurrence of gadolinium-enhancing lesions on MRI. Secondary endpoints were new/enlarging T2 lesions on MRI and relapses and progression on the Expanded Disability Status Scale (EDSS) during follow-up and extension phase. RESULTS: Sixty-one patients were included. Eighty-four percent extended the interval from a 4-week interval to a 5- to 7-week interval. No patient developed gadolinium-enhancing lesions (95% confidence interval [CI] 0%-7.4%) during follow-up. No new/enlarging T2 lesions (95% CI 0%-7.4%) or relapses (95% CI 0%-7.4%) were reported during follow-up and in the extension phase. Median EDSS was comparable at baseline (3.0, interquartile range [IQR] 2.0-5.0) and after follow-up (3.0, IQR 2.0-5.0). CONCLUSION: Personalized extended interval dosing did not induce recurrence of MS disease activity. Natalizumab efficacy was maintained in stable patients with RRMS receiving personalized extended interval dosing based on individual natalizumab concentrations. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that personalized extended interval dosing of natalizumab does not result in recurrence of disease activity in stable patients with RRMS.


Asunto(s)
Esclerosis Múltiple/tratamiento farmacológico , Natalizumab/administración & dosificación , Adulto , Evaluación de la Discapacidad , Esquema de Medicación , Monitoreo de Drogas , Femenino , Estudios de Seguimiento , Humanos , Integrina alfa4beta1/antagonistas & inhibidores , Integrina alfa4beta1/inmunología , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Esclerosis Múltiple/sangre , Esclerosis Múltiple/diagnóstico por imagen , Natalizumab/sangre , Natalizumab/uso terapéutico , Países Bajos , Neuroimagen , Medicina de Precisión , Estudios Prospectivos , Índice de Severidad de la Enfermedad
6.
Brasília; s.n; 15 jun. 2020.
No convencional en Portugués | LILACS, BRISA/RedTESA, PIE | ID: biblio-1100400

RESUMEN

O Informe Diário de Evidências é uma produção do Ministério da Saúde que tem como objetivo acompanhar diariamente as publicações científicas sobre tratamento farmacológico e vacinas para a COVID-19. Dessa forma, são realizadas buscas estruturadas em bases de dados biomédicas, referente ao dia anterior desse informe. Não são incluídos estudos pré-clínicos (in vitro, in vivo, in silico). A frequência dos estudos é demonstrada de acordo com a sua classificação metodológica (revisões sistemáticas, ensaios clínicos randomizados, coortes, entre outros). Para cada estudo é apresentado um resumo com avaliação da qualidade metodológica. Essa avaliação tem por finalidade identificar o grau de certeza/confiança ou o risco de viés de cada estudo. Para tal, são utilizadas ferramentas já validadas e consagradas na literatura científica, na área de saúde baseada em evidências. Cabe ressaltar que o documento tem caráter informativo e não representa uma recomendação oficial do Ministério da Saúde sobre a temática. Foram encontrados 15 artigos.


Asunto(s)
Humanos , Neumonía Viral/tratamiento farmacológico , Infecciones por Coronavirus/tratamiento farmacológico , Betacoronavirus/efectos de los fármacos , Sistema Renina-Angiotensina , Evaluación de la Tecnología Biomédica , Ceftriaxona/uso terapéutico , Inmunoglobulinas/uso terapéutico , Metilprednisolona/uso terapéutico , Ciclosporina/uso terapéutico , Azitromicina/uso terapéutico , Ritonavir/uso terapéutico , Oseltamivir/uso terapéutico , Lopinavir/uso terapéutico , Natalizumab/uso terapéutico , Glucocorticoides/uso terapéutico , Hidroxicloroquina/uso terapéutico
7.
Brain Nerve ; 72(5): 517-523, 2020 May.
Artículo en Japonés | MEDLINE | ID: mdl-32381749

RESUMEN

Multiple sclerosis disease modifying drugs (MS-DMD) currently used in Japan are interferon ß-1a, interferon ß-1b and gratiramer acetate, fingolimod, dimethyl furmarate, and natalizumab. Ofatumumab and siponimod will be approved probably in 2021. Ofatumumab is an ant-CD20 human monoclonal antibody. A clinical trial revealed that the efficacy of ofatumumab is clearly superior to teriflunomide that has comparable efficacy to dimethyl fumarate. Siponimod, a selective sphingosine-1-phosphate receptor modulator, exhibited mild, but significant efficacy for secondary progressive form of MS. OCH, a synthetic glycolipid agent, is being tested in phase II clinical trials in Japan. What DMD is to select is challenging since MS prognosis varies and is unexpected. Only very few have truly benign course without treatment. Silent progression should be considered especially in cases with those with interferon ß-1a, interferon ß-1b and gratiramer acetate. Escalation therapy is more widely accepted than initiation of high efficacy therapy in Japan because emphasizing safety. In such strategy three injectables and dimethyl fumarate are regarded as first line therapies. On the other hand, initiation of high efficacy drugs may be reasonable to prevent from disease progression. Even if either is acceptable, early induction of DMD with sufficient efficacy is mandatory for MS treatment.


Asunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Azetidinas/uso terapéutico , Compuestos de Bencilo/uso terapéutico , Dimetilfumarato/uso terapéutico , Esclerosis Múltiple/tratamiento farmacológico , Ensayos Clínicos como Asunto , Clorhidrato de Fingolimod/uso terapéutico , Acetato de Glatiramer/uso terapéutico , Humanos , Interferones/uso terapéutico , Japón , Natalizumab/uso terapéutico
9.
Mult Scler Relat Disord ; 43: 102174, 2020 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-32464584

RESUMEN

BACKGROUND: SARS-CoV-2 viral infection causes COVID-19 that can result in severe acute respiratory distress syndrome (ARDS), which can cause significant mortality, leading to concern that immunosuppressive treatments for multiple sclerosis and other disorders have significant risks for both infection and ARDS. OBJECTIVE: To examine the biology that potentially underpins immunity to the SARS-Cov-2 virus and the immunity-induced pathology related to COVID-19 and determine how this impinges on the use of current disease modifying treatments in multiple sclerosis. OBSERVATIONS: Although information about the mechanisms of immunity are scant, it appears that monocyte/macrophages and then CD8 T cells are important in eliminating the SARS-CoV-2 virus. This may be facilitated via anti-viral antibody responses that may prevent re-infection. However, viral escape and infection of leucocytes to promote lymphopenia, apparent CD8 T cell exhaustion coupled with a cytokine storm and vascular pathology appears to contribute to the damage in ARDS. IMPLICATIONS: In contrast to ablative haematopoietic stem cell therapy, most multiple-sclerosis-related disease modifying therapies do not particularly target the innate immune system and few have any major long-term impact on CD8 T cells to limit protection against COVID-19. In addition, few block the formation of immature B cells within lymphoid tissue that will provide antibody-mediated protection from (re)infection. However, adjustments to dosing schedules may help de-risk the chance of infection further and reduce the concerns of people with MS being treated during the COVID-19 pandemic.


Asunto(s)
Betacoronavirus/inmunología , Linfocitos T CD8-positivos/inmunología , Infecciones por Coronavirus/inmunología , Síndrome de Liberación de Citoquinas/inmunología , Inmunosupresores/uso terapéutico , Linfopenia/inmunología , Esclerosis Múltiple/terapia , Neumonía Viral/inmunología , Alemtuzumab/uso terapéutico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Antivirales/inmunología , Cladribina/uso terapéutico , Crotonatos/uso terapéutico , Deprescripciones , Dimetilfumarato/uso terapéutico , Clorhidrato de Fingolimod/uso terapéutico , Acetato de Glatiramer/uso terapéutico , Trasplante de Células Madre Hematopoyéticas/métodos , Humanos , Evasión Inmune/inmunología , Inmunidad Innata/inmunología , Factores Inmunológicos/uso terapéutico , Interferón beta/uso terapéutico , Macrófagos/inmunología , Monocitos/inmunología , Natalizumab/uso terapéutico , Pandemias , Toluidinas/uso terapéutico
11.
Mult Scler Relat Disord ; 43: 102195, 2020 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-32460086

RESUMEN

OBJECTIVE: To determine whether the course of COVID-19 is more severe in patients with MS and if MS disease-modifying treatments (DMTs) affect the risk of contracting the disease. METHODS: In a cross-sectional survey, data were collected by sending a questionnaire to 2000 patients with a demyelinating disease through an online portal system. Collected data included the current MS DMT and patient-reported disability level, history of recent sick contact, recent fever, respiratory symptoms, diagnosis with COVID-19, and the disposition after the diagnosis. We defined a COVID-19-suspect group as patients having fever and cough or fever and shortness of breath, or a presumptive diagnosis based on suggestive chest computed tomography. We calculated the proportion of COVID-19-suspect patients and compared their demographics, clinical characteristics, and DMT categories with the rest of survey-responders, using univariable and multivariable models. RESULTS: Out of 712 patients, 34 (4.8%) fulfilled our criteria for being in the COVID-19-suspect group. Only two patients required hospitalization. No patient required intensive care. In a multivariable model, disease duration (p-value=0.017), DMT category (p-value=0.030), and history of sick contact (p-values<0.001) were associated with the risk of being in the COVID-19-suspect group. Being on B-cell depleting antibodies (as compared to non-cell depleting, non-cell trafficking inhibitor DMTs) was associated with a 2.6-fold increase in the risk of being in the COVID-19-suspect group. (RR: 3.55, 95%CI: 1.45, 8.68, p-value=0.005). CONCLUSIONS: The course of infection in patients with MS suspected of having COVID-19 was mild to moderate, and all patients had a full recovery. B-cell depleting antibodies may increase the susceptibility to contracting COVID-19.


Asunto(s)
Infecciones por Coronavirus/inmunología , Huésped Inmunocomprometido/inmunología , Factores Inmunológicos/uso terapéutico , Esclerosis Múltiple/tratamiento farmacológico , Neumonía Viral/inmunología , Adulto , Anticuerpos Monoclonales Humanizados/uso terapéutico , Linfocitos B/inmunología , Betacoronavirus , Infecciones por Coronavirus/complicaciones , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/fisiopatología , Tos , Estudios Transversales , Crotonatos/uso terapéutico , Dimetilfumarato/uso terapéutico , Susceptibilidad a Enfermedades , Disnea , Epidemias , Femenino , Fiebre , Clorhidrato de Fingolimod/uso terapéutico , Acetato de Glatiramer/uso terapéutico , Hospitalización/estadística & datos numéricos , Humanos , Unidades de Cuidados Intensivos/estadística & datos numéricos , Interferones/uso terapéutico , Irán/epidemiología , Pulmón/diagnóstico por imagen , Depleción Linfocítica , Masculino , Esclerosis Múltiple/complicaciones , Esclerosis Múltiple Crónica Progresiva/tratamiento farmacológico , Esclerosis Múltiple Crónica Progresiva/epidemiología , Esclerosis Múltiple Recurrente-Remitente/tratamiento farmacológico , Esclerosis Múltiple Recurrente-Remitente/epidemiología , Natalizumab/uso terapéutico , Pandemias , Neumonía Viral/complicaciones , Neumonía Viral/epidemiología , Neumonía Viral/fisiopatología , Rituximab/uso terapéutico , Índice de Severidad de la Enfermedad , Toluidinas/uso terapéutico , Tomografía Computarizada por Rayos X
12.
Neurology ; 94(22): e2373-e2383, 2020 06 02.
Artículo en Inglés | MEDLINE | ID: mdl-32430312

RESUMEN

OBJECTIVE: Disease-modifying treatments (DMTs) are the gold standard for slowing disability progression in multiple sclerosis (MS), but their effects on cognitive impairment, a key symptom of the disease, are mostly unknown. We conducted a systematic review and meta-analysis to evaluate the differential effects of DMTs on cognitive test performance in relapsing-remitting MS (RRMS). METHODS: PubMed, Scopus, and Cochrane Library were searched for studies reporting longitudinal cognitive performance data related to all major DMTs. The standardized mean difference (Hedges g) between baseline and follow-up cognitive assessment was used as the main effect size measure. RESULTS: Forty-four studies, including 55 distinct MS patient samples, were found eligible for the systematic review. Twenty-five studies were related to platform therapies (mainly ß-interferon [n = 17] and glatiramer acetate [n = 4]), whereas 22 studies were related to escalation therapies (mainly natalizumab [n = 14] and fingolimod [n = 6]). Reported data were mostly confined to the cognitive domain processing speed. A meta-analysis including 41 studies and 7,131 patients revealed a small to moderate positive effect on cognitive test performance of DMTs in general (g = 0.27, 95% confidence interval [CI] = [0.21-0.33]), but no statistically significant differences between platform (g = 0.27, 95% CI = [0.18-0.35]) and escalation therapies (g = 0.28, 95% CI = [0.19-0.37]) or between any single DMT and ß-interferon. CONCLUSIONS: DMTs are effective in improving cognitive test performance in RRMS, but a treatment escalation mainly to amend cognition is not supported by the current evidence. Given the multitude of DMTs and their widespread use, the available data regarding differential treatment effects on cognitive impairment are remarkably scant. Clinical drug trials that use more extensive cognitive outcome measures are urgently needed.


Asunto(s)
Cognición/efectos de los fármacos , Disfunción Cognitiva/tratamiento farmacológico , Inmunosupresores/uso terapéutico , Esclerosis Múltiple Recurrente-Remitente/tratamiento farmacológico , Cognición/fisiología , Disfunción Cognitiva/epidemiología , Disfunción Cognitiva/psicología , Clorhidrato de Fingolimod/farmacología , Clorhidrato de Fingolimod/uso terapéutico , Acetato de Glatiramer/farmacología , Acetato de Glatiramer/uso terapéutico , Humanos , Factores Inmunológicos/farmacología , Factores Inmunológicos/uso terapéutico , Inmunosupresores/farmacología , Interferón beta/farmacología , Interferón beta/uso terapéutico , Esclerosis Múltiple Recurrente-Remitente/epidemiología , Esclerosis Múltiple Recurrente-Remitente/psicología , Natalizumab/farmacología , Natalizumab/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como Asunto/métodos
13.
Neurology ; 94(23): e2468-e2478, 2020 06 09.
Artículo en Inglés | MEDLINE | ID: mdl-32434868

RESUMEN

OBJECTIVE: To evaluate the frequency of asymptomatic optic nerve lesions and their role in the asymptomatic retinal neuroaxonal loss observed in multiple sclerosis (MS). METHODS: We included patients with remitting-relapsing MS in the VWIMS study (Analysis of Neurodegenerative Process Within Visual Ways In Multiple Sclerosis) (ClinicalTrials.gov Identifier: 03656055). Included patients underwent optical coherence tomography (OCT), optic nerve and brain MRI, and low-contrast visual acuity measurement. In eyes of patients with MS without optic neuritis (MS-NON), an optic nerve lesion on MRI (3D double inversion recovery [DIR] sequence) was considered as an asymptomatic lesion. We considered the following OCT/MRI measures: peripapillary retinal nerve fiber layer thickness, macular ganglion cell + inner plexiform layer (mGCIPL) volumes, optic nerve lesion length, T2 lesion burden, and fractional anisotropy within optic radiations. RESULTS: An optic nerve lesion was detected in half of MS-NON eyes. Compared to optic nerves without any lesion and independently of the optic radiation lesions, the asymptomatic lesions were associated with thinner inner retinal layers (p < 0.0001) and a lower contrast visual acuity (p ≤ 0.003). Within eyes with asymptomatic optic nerve lesions, optic nerve lesion length was the only MRI measure significantly associated with retinal neuroaxonal loss (p < 0.03). Intereye mGCIPL thickness difference (IETD) was lower in patients with bilateral optic nerve DIR hypersignal compared to patients with unilateral hypersignal (p = 0.0317). For the diagnosis of history of optic neuritis, sensitivity of 3D DIR and of mGCIPL IETD were 84.9% and 63.5%, respectively. CONCLUSIONS: Asymptomatic optic nerve lesions are an underestimated and preponderant cause of retinal neuroaxonal loss in MS. 3D DIR sequence may be more sensitive than IETD measured by OCT for the detection of optic nerve lesions.


Asunto(s)
Esclerosis Múltiple/patología , Nervio Óptico/patología , Retina/patología , Adolescente , Adulto , Anciano , Anisotropía , Enfermedades Asintomáticas , Atrofia , Sensibilidad de Contraste , Estudios Transversales , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Esclerosis Múltiple/complicaciones , Esclerosis Múltiple/diagnóstico por imagen , Esclerosis Múltiple/tratamiento farmacológico , Natalizumab/uso terapéutico , Fibras Nerviosas/patología , Neuroimagen , Nervio Óptico/diagnóstico por imagen , Tamaño de los Órganos , Proyectos Piloto , Retina/diagnóstico por imagen , Degeneración Retiniana/etiología , Degeneración Retiniana/patología , Sensibilidad y Especificidad , Tomografía de Coherencia Óptica , Corteza Visual/diagnóstico por imagen , Corteza Visual/patología , Adulto Joven
14.
Brasília; s.n; 12 maio 2020.
No convencional en Portugués | LILACS, BRISA/RedTESA, PIE | ID: biblio-1097394

RESUMEN

Essa é uma produção do Departamento de Ciência e Tecnologia (Decit) da Secretaria de Ciência, Tecnologia, Inovação e Insumos Estratégicos em Saúde (SCTIE) do Ministério da Saúde (Decit/SCTIE/MS), que tem como missão promover a ciência e tecnologia e o uso de evidências científicas para a tomada de decisão do SUS, tendo como principal atribuição o incentivo ao desenvolvimento de pesquisas em saúde no Brasil, de modo a direcionar os investimentos realizados em pesquisa pelo Governo Federal às necessidades de saúde pública. Informar sobre as principais evidências científicas descritas na literatura internacional sobre tratamento farmacológico para a COVID-19. Além de resumir cada estudo identificado, o informe apresenta também uma avaliação da qualidade metodológica e a quantidade de artigos publicados, de acordo com a sua classificação metodológica (revisões sistemáticas, ensaios clínicos randomizados, entre outros). Foram encontrados 12 artigos e 15 protocolos.


Asunto(s)
Humanos , Neumonía Viral/tratamiento farmacológico , Infecciones por Coronavirus/tratamiento farmacológico , Betacoronavirus/efectos de los fármacos , Vacunas/uso terapéutico , Azitromicina/uso terapéutico , Progresión de la Enfermedad , Ritonavir/uso terapéutico , Lopinavir/uso terapéutico , Natalizumab/uso terapéutico , Hidroxicloroquina/uso terapéutico
15.
J Neurol Neurosurg Psychiatry ; 91(6): 660-668, 2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-32234967

RESUMEN

OBJECTIVE: The Tysabri Observational Programme (TOP), which began >10 years ago, is an open-label, multinational, prospective observational study evaluating the long-term safety and effectiveness of natalizumab in relapsing-remitting multiple sclerosis patients. METHODS: These data provide a 10-year interim analysis of safety and effectiveness in TOP. Annualised relapse rates (ARRs) and disability progression/improvement were analysed using the Poisson model and the Kaplan-Meier method, respectively. Analyses included patients on natalizumab and those who discontinued natalizumab but remained in TOP. RESULTS: As of November 2017, TOP included 6148 patients. Overall, 829 patients (13.5%) experienced ≥1 serious adverse event (SAE), with infection the most common (4.1%). Fifty-three patients (0.9%) had confirmed progressive multifocal leukoencephalopathy. SAE data were consistent with natalizumab's known safety profile; no new safety signals were identified. A total of 3210 patients (52.2%) discontinued natalizumab; 2117 (34.4%) withdrew from TOP. Median time on natalizumab was 3.3 (range 0-11.6) years; median follow-up time was 5.2 (range 0-10.8) years. The on-natalizumab ARR was 0.15, a 92.5% reduction from the year before initiation. Ten-year cumulative probabilities of disability worsening and improvement were 27.8% and 33.1%, respectively. On-natalizumab ARRs were similar between patients who discontinued or remained on natalizumab, suggesting limited attrition bias. CONCLUSIONS: Since the TOP 5-year interim analysis (December 2012), cohort size (6148 vs 4821), median exposure (3.3 vs 1.8 years) and median follow-up time (62 vs 26 months) have increased. This 10-year interim analysis further supports the robust real-world effectiveness and well-established safety profile of natalizumab. TRIAL REGISTRATION NUMBER: NCT00493298.


Asunto(s)
Factores Inmunológicos/uso terapéutico , Esclerosis Múltiple Recurrente-Remitente/tratamiento farmacológico , Natalizumab/uso terapéutico , Adulto , Evaluación de la Discapacidad , Progresión de la Enfermedad , Femenino , Humanos , Factores Inmunológicos/efectos adversos , Masculino , Persona de Mediana Edad , Natalizumab/efectos adversos , Resultado del Tratamiento
16.
PLoS One ; 15(4): e0230846, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32240213

RESUMEN

PURPOSE: The objective of this study was to characterize the demographic and clinical profile of RRMS patients receiving fingolimod in Spain, and to evaluate drug effectiveness and safety in clinical practice. METHODS: This observational, retrospective, multicentre, nationwide study was performed at 56 Spanish hospitals and involved 804 RRMS patients who received oral fingolimod (0.5 mg) since November 2011, with a minimum follow-up of 12 months. RESULTS: The mean annualized relapse rate (ARR) in the year before fingolimod was 1.08 and the median EDSS was 3; patients were exposed to fingolimod for 2.2 years as average; regarding magnetic resonance imaging (MRI) activity, more than half of the patients had >20 lesions at baseline. Patients were previously treated with first-line injectable DMTs (60.3%), or natalizumab (31.3%), and 8.3% were naïve patients. Overall, the ARR significantly decreased to 0.28, 0.22 and 0.17 (74.1%, 79.7% and 83.5% of relative reduction, respectively) after 12, 24 and 36 months of treatment, P<0.001. The ARR of patients who switched from natalizumab to fingolimod was stable over the study. Most of the patients (88.7%) were free from confirmed disability and MRI activity (67.3%) after 24 months. The persistence after 12 months on fingolimod was 93.9%. CONCLUSIONS: The subgroups of patients analysed showed differential baseline demographic and clinical characteristics. The analysis of patients who received fingolimod in routine clinical practice confirmed adequate efficacy and safety, even for long-term treatment. The present data also confirmed the positive benefit/risk balance with fingolimod in real-world clinical practice setting.


Asunto(s)
Clorhidrato de Fingolimod/uso terapéutico , Esclerosis Múltiple/tratamiento farmacológico , Adulto , Anciano , Personas con Discapacidad , Femenino , Clorhidrato de Fingolimod/metabolismo , Humanos , Inmunosupresores/uso terapéutico , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Esclerosis Múltiple Recurrente-Remitente/tratamiento farmacológico , Natalizumab/uso terapéutico , Recurrencia , Estudios Retrospectivos , España
17.
J Neurol Neurosurg Psychiatry ; 91(5): 493-502, 2020 05.
Artículo en Inglés | MEDLINE | ID: mdl-32111638

RESUMEN

OBJECTIVE: To compare the efficacy of fingolimod and natalizumab in preventing regional grey matter (GM) and white matter (WM) atrophy in relapsing-remitting multiple sclerosis (RRMS) over 2 years. METHODS: Patients with RRMS starting fingolimod (n=25) or natalizumab (n=30) underwent clinical examination and 3T MRI scans at baseline (month (M) 0), M6, M12 and M24. Seventeen healthy controls were also scanned at M0 and M24. Tensor-based morphometry and SPM12 were used to assess the longitudinal regional GM/WM volume changes. RESULTS: At M0, no clinical or GM/WM volume differences were found between treatment groups. At M24, both drugs reduced relapse rate (p<0.001 for both) and stabilised disability. At M6 vs M0, both groups experienced significant atrophy of several areas in the cortex, deep GM nuclei and supratentorial WM. Significant bilateral cerebellar GM and WM atrophy occurred in fingolimod patients only. At M12 vs M6 and M24 vs M12, further supratentorial GM and WM atrophy occurred in both groups. Bilateral GM/WM cerebellar atrophy continued to progress in fingolimod patients only. Compared with natalizumab, fingolimod-treated patients showed a significant cerebellar GM/WM atrophy, mainly at M6 vs M0, but still occurring up to M24. Compared with fingolimod, natalizumab-treated patients had a small number of areas of GM atrophy in temporo-occipital regions at the different time-points. CONCLUSIONS: Natalizumab and fingolimod are associated with heterogeneous temporal and regional patterns of GM and WM atrophy progression. Compared with natalizumab, fingolimod-treated patients experience accelerated GM and WM atrophy in the cerebellum, while both drugs show minimal regional volumetric differences in supratentorial regions.


Asunto(s)
Clorhidrato de Fingolimod/uso terapéutico , Sustancia Gris/efectos de los fármacos , Factores Inmunológicos/uso terapéutico , Esclerosis Múltiple Recurrente-Remitente/tratamiento farmacológico , Natalizumab/uso terapéutico , Sustancia Blanca/efectos de los fármacos , Adulto , Atrofia , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Progresión de la Enfermedad , Femenino , Sustancia Gris/diagnóstico por imagen , Sustancia Gris/patología , Humanos , Estudios Longitudinales , Imagen por Resonancia Magnética , Masculino , Esclerosis Múltiple Recurrente-Remitente/diagnóstico por imagen , Esclerosis Múltiple Recurrente-Remitente/patología , Neuroimagen , Estudios Prospectivos , Sustancia Blanca/diagnóstico por imagen , Sustancia Blanca/patología
18.
Eur Neurol ; 83(1): 25-33, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32187609

RESUMEN

BACKGROUND: There is a lack of head-to-head studies comparing the efficacy of fingolimod (FIN) and natalizumab (NTZ) as second-line therapy for relapsing-remitting multiple sclerosis (RRMS). METHODS: Multicenter, observational study, in which, information of 388 patients randomly selected and treated with FIN or NTZ in routine clinical practice was retrospectively collected with the main objective of comparing the annualized relapse rate (ARR) over the first year, after FIN or NTZ treatment initiation. RESULTS: Mean ARR during the first year of treatment was 0.28 in FIN group and 0.12 in NTZ group (p = 0.0064); nevertheless, the difference between groups lost statistical significance when the propensity score analysis was performed. Time to disability -progression was similar in both treatment groups (12.3 ± 6.7 months in FIN, and 12.8 ± 0.1 months in NTZ; p = 0.4654). Treatment persistence after the first year of treatment was higher in patients treated with FIN (95%) than in those treated with NTZ (84%; p = 0.0014). CONCLUSIONS: After 12 months of treatment, both FIN and NTZ reduced the ARR, but ARR percent reduction was significantly higher with NTZ. Treatment persistence was higher in patients receiving FIN.


Asunto(s)
Clorhidrato de Fingolimod/uso terapéutico , Inmunosupresores/uso terapéutico , Esclerosis Múltiple Recurrente-Remitente/tratamiento farmacológico , Natalizumab/uso terapéutico , Adulto , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Recurrencia , Estudios Retrospectivos , España
19.
PLoS One ; 15(3): e0229768, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32119696

RESUMEN

PURPOSE: In the Brazilian public healthcare system, natalizumab is recommended as fourth-line treatment for relapsing-remitting multiple sclerosis (RRMS). Although natalizumab has already demonstrated higher effectiveness compared with fingolimod in some studies, this real-world study was conducted to evaluate annualized hospitalization rates (AHR) in Brazil for both treatments when switching from platform therapies. As secondary goals, we analyzed RRMS treatment patterns and hospitalization profiles. MATERIAL AND METHODS: We extracted data from the DATASUS database of patients with MS (ICD-10 G35) who initiated treatment from January 2012 to December 2017. Two cohorts were screened for different purposes. Cohort 1 was used to analyze treatment patterns and hospitalization profiles and was defined as individuals who had at least one claim related to MS therapies and had received at least two lines of treatment. The second cohort, which was a subset of the first, was used to compare natalizumab's and fingolimod's AHR reduction from previous treatment lines and included patients switching from platform therapy to one of these two drugs. Cohort 2 adjustment was assessed through two different statistical methods: propensity score (PS) and inverse probability weighting (IPW). RESULTS: Of 29,410 patients screened, 2,876 were included in cohort 1. Three quarters of hospitalizations reported in this cohort were for treatment of MS relapse. Cohort 2 included 1,005 patients, and natalizumab was more commonly used (n = 540) than fingolimod (n = 465). Both PS and IPW analyses showed that patients treated with natalizumab had a statistical significantly reduction in AHR compared with first-line treatment (p<0.01 for both PS and IPW), while fingolimod did not result in significant reduction in AHR (p = 0.20 for PS and p = 0.17 for IPW). CONCLUSION: This study provides real-world evidence of natalizumab's and fingolimod's effectiveness in terms of AHR, with an increased reduction in AHR with natalizumab. The findings of this study also provide information to support disease management and healthcare planning in the Brazilian public healthcare system.


Asunto(s)
Clorhidrato de Fingolimod/uso terapéutico , Inmunosupresores/uso terapéutico , Esclerosis Múltiple Recurrente-Remitente/tratamiento farmacológico , Natalizumab/uso terapéutico , Reclamos Administrativos en el Cuidado de la Salud/estadística & datos numéricos , Adulto , Anciano , Brasil , Femenino , Clorhidrato de Fingolimod/administración & dosificación , Clorhidrato de Fingolimod/efectos adversos , Hospitalización/estadística & datos numéricos , Hospitales Públicos/estadística & datos numéricos , Humanos , Inmunosupresores/administración & dosificación , Inmunosupresores/efectos adversos , Masculino , Persona de Mediana Edad , Natalizumab/administración & dosificación , Natalizumab/efectos adversos
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