Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.516
Filtrar
3.
Nat Med ; 25(9): 1402-1407, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31501610

RESUMO

Natalizumab (NZM), a humanized monoclonal IgG4 antibody to α4 integrins, is used to treat patients with relapsing-remitting multiple sclerosis (MS)1,2, but in about 6% of the cases persistent neutralizing anti-drug antibodies (ADAs) are induced leading to therapy discontinuation3,4. To understand the basis of the ADA response and the mechanism of ADA-mediated neutralization, we performed an in-depth analysis of the B and T cell responses in two patients. By characterizing a large panel of NZM-specific monoclonal antibodies, we found that, in both patients, the response was polyclonal and targeted different epitopes of the NZM idiotype. The neutralizing activity was acquired through somatic mutations and correlated with a slow dissociation rate, a finding that was supported by structural data. Interestingly, in both patients, the analysis of the CD4+ T cell response, combined with mass spectrometry-based peptidomics, revealed a single immunodominant T cell epitope spanning the FR2-CDR2 region of the NZM light chain. Moreover, a CDR2-modified version of NZM was not recognized by T cells, while retaining binding to α4 integrins. Collectively, our integrated analysis identifies the basis of T-B collaboration that leads to ADA-mediated therapeutic resistance and delineates an approach to design novel deimmunized antibodies for autoimmune disease and cancer treatment.


Assuntos
Anticorpos Neutralizantes/administração & dosagem , Epitopos de Linfócito T/imunologia , Esclerose Múltipla/tratamento farmacológico , Natalizumab/administração & dosagem , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Neutralizantes/química , Formação de Anticorpos/efeitos dos fármacos , Formação de Anticorpos/imunologia , Linfócitos B/efeitos dos fármacos , Humanos , Imunoglobulina G/química , Imunoglobulina G/imunologia , Integrina alfa4/antagonistas & inibidores , Integrina alfa4/imunologia , Esclerose Múltipla/imunologia , Esclerose Múltipla/patologia , Conformação Proteica/efeitos dos fármacos , Linfócitos T/química , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia
5.
J. bras. econ. saúde (Impr.) ; 11(2): 128-134, Agosto/2019.
Artigo em Português | LILACS, ECOS | ID: biblio-1021106

RESUMO

Objetivos: Os objetivos deste estudo são calcular o custo de um surto de esclerose múltipla sob a perspectiva de uma operadora de saúde privada e o impacto orçamentário da adoção de natalizumabe em primeira linha para esclerose múltipla remitente-recorrente altamente ativa (EMRRAA). Métodos: Para o cálculo do custo do surto, duas abordagens foram adotadas: para surtos que não levam a hospitalizações, foi aplicada uma pesquisa a 33 médicos neurologistas para identificação do consumo de recursos. Microcusteio foi realizado com base em bases de dados públicas. Para o cálculo do custo de surtos que levam a hospitalizações, foi utilizada uma base de contas médicas. Para o cálculo do impacto orçamentário, foi construído um modelo baseado em prevalência. Foram assumidos os seguintes custos: custo de aquisição de natalizumabe, custo de infusão de natalizumabe e custo de surtos. Taxa de ocorrência de surtos para natalizumabe e para seus comparadores, disponível apenas no sistema público, foi obtida em estudos clínicos e metanálises. O caso-base foi realizado considerando-se uma operadora que atende 100 mil vidas na região Sudeste. Análise de sensibilidade foi realizada. Resultados: O custo calculado de um surto foi de R$ 14.157,21. O impacto orçamentário calculado para adoção de natalizumabe para EMRRAA foi de R$ 0,64 por beneficiário por ano, ou 0,02% das despesas assistenciais de uma operadora de saúde suplementar, ou 0,02% de suas receitas de contraprestações. A análise de sensibilidade confirma que o impacto não chega a 1 real por beneficiário por ano e atinge, no máximo, 0,03% das despesas assistenciais. Conclusão: Dados os altos benefícios clínicos de natalizumabe, o impacto orçamentário de sua adoção para primeira linha de EMRRAA é considerado baixo. O impacto pode estar superestimado, visto que não foram considerados custos de progressão da doença.


Objetivos: The goals of this study are to evaluate the cost of a multiple sclerosis relapse and the budget impact of adopting natalizumab as first-line therapy for HARRMS, both from a private payer perspective. Methods: For calculating the cost of a relapse, two approaches were adopted: for relapses not resulting in hospitalizations, a research with 33 physicians was made to obtain resource utilization data. Microcosting was performed using public data sources. For calculating costs of relapses leading to hospitalizations, we analyzed a claims database. To calculate the budget impact of adopting natalizumab as per its label indication, we built a prevalence-based model. The following costs were included: drug acquisition, drug infusion and relapses costs. The relapses rates for natalizumab and its comparators present in the public system were calculated based on clinical trials and meta-analysis. The base case was calculated assuming a hypothetical payer covering one hundred lives in the southeastern region of Brazil. Sensitivity analysis was performed. Results: The calculated relapse cost was R$ 14,157.21. The calculated budget impact for adopting natalizumab for HARRMS was R$ 0.64 per person per year, or 0.02% of the payer's healthcare expenditures, or 0.02% of its revenue. The sensibility analysis confirmed that the budget impact does not reach one real per person per year and does not exceed 0.03% of healthcare expenses. Conclusion: Given the high clinical benefits of adopting Tysabri, its budget impact can be considered low. The results might be overestimated, since disability progression costs were not accounted in the calculations


Assuntos
Humanos , Sistemas de Saúde , Saúde Suplementar , Natalizumab , Esclerose Múltipla
6.
Rinsho Shinkeigaku ; 59(8): 536-540, 2019 Aug 29.
Artigo em Japonês | MEDLINE | ID: mdl-31341130

RESUMO

A 42-year-old woman diagnosed with multiple sclerosis (MS) at the age of 37 was initially treated with interferon-ß IM. The frequency of clinical relapses was twice in 4 years. At the age of 41, due to difficulty in administering muscle injections, an oral medication fingolimod was started. However, it was discontinued after a month due to decreased lymphocyte count, following which natalizumab was administered. The number of relapses increased 3 times in eleven months, and the number of T2 lesions on the MRI increased from 12 to 23. Natalizumab was discontinued because the test for the anti-natalizumab antibody was positive. It was suspected that both, the rebound syndrome caused by fingolimod cessation and the drug neutralization by anti-natalizumab antibodies, were associated with the exacerbation of disease activity. Thus, careful attention should be paid to potential occurrence of these events post switching between disease-modifying drugs for treating MS with high activity.


Assuntos
Substituição de Medicamentos/efeitos adversos , Cloridrato de Fingolimode/administração & dosagem , Cloridrato de Fingolimode/efeitos adversos , Fatores Imunológicos/administração & dosagem , Fatores Imunológicos/efeitos adversos , Imunossupressores/administração & dosagem , Imunossupressores/efeitos adversos , Esclerose Múltipla/tratamento farmacológico , Esclerose Múltipla/imunologia , Natalizumab/administração & dosagem , Natalizumab/efeitos adversos , Adulto , Anticorpos , Progressão da Doença , Feminino , Humanos , Injeções Intramusculares , Interferon beta/administração & dosagem , Contagem de Linfócitos , Natalizumab/imunologia , Recidiva
7.
BMC Neurol ; 19(1): 116, 2019 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-31176355

RESUMO

BACKGROUND: STRIVE is a multicenter, observational, open-label, single-arm study of natalizumab in anti-JC virus (JCV) seronegative patients with early relapsing-remitting multiple sclerosis (RRMS). The objective of this prespecified 2-year interim analysis was to determine the effectiveness of natalizumab in establishing and maintaining no evidence of disease activity (NEDA) in early RRMS. METHODS: Patients aged 18-65 years had an RRMS diagnosis < 3 years prior to screening, an Expanded Disability Status Scale (EDSS) score ≤ 4.0, and anti-JCV antibody negative status. Magnetic resonance imaging was performed at baseline and yearly thereafter. Cumulative probabilities of 24-week-confirmed EDSS worsening and improvement were evaluated at 2 years. NEDA (no 24-week-confirmed EDSS worsening, no relapses, no gadolinium-enhancing lesions, and no new/newly enlarging T2-hyperintense lesions) was evaluated over 2 years. The Symbol Digit Modalities Test (SDMT) and Multiple Sclerosis Impact Score (MSIS-29) were assessed at baseline and 1 and 2 years. Statistical analysis used summary statistics and frequency distributions. RESULTS: The study population (N = 222) had early RRMS, with mean (standard deviation [SD]) time since diagnosis of 1.6 (0.77) years and mean (SD) baseline EDSS score of 2.0 (1.13). NEDA was achieved in 105 of 187 patients (56.1%) during year 1 and 120 of 163 (73.6%) during year 2. Over 2 years, 76 of 171 patients (44.4%) attained overall NEDA. Probabilities of 24-week-confirmed EDSS worsening and improvement were 14.1% and 28.4%, respectively. After 2 years, patients exhibited significant improvements from baseline in SDMT (n = 158; mean [SD]: 4.3 [11.8]; p < 0.001) and MSIS-29 physical (n = 153; mean [SD]: - 3.9 [14.7]; p = 0.001), psychological (n = 152; mean [SD]: - 2.0 [7.9]; p < 0.001), and quality-of-life (n = 153; mean [SD]: - 6.0 [21.3]; p < 0.001) scores. CONCLUSIONS: These results support natalizumab's effectiveness over 2 years, during which nearly half of early RRMS patients achieved NEDA. During year 2, nearly 75% of patients exhibited NEDA. Over 2 years, patients continued to experience significant cognitive and quality-of-life benefits. These results are limited by the lack of a comparator group to determine the extent of a placebo effect. TRIAL REGISTRATION: clinicaltrials.gov, NCT01485003 , registered 5 December 2011.


Assuntos
Fatores Imunológicos/farmacologia , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Natalizumab/farmacologia , Adulto , Feminino , Humanos , Fatores Imunológicos/administração & dosagem , Masculino , Pessoa de Meia-Idade , Natalizumab/administração & dosagem , Fatores de Tempo
8.
Mult Scler Relat Disord ; 33: 82-87, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31174043

RESUMO

BACKGROUND: Natalizumab is an effective treatment for relapsing-remitting multiple sclerosis (RRMS). Data on clinical and imaging measures predictive of disease activity and progression during treatment is limited. OBJECTIVE: To determine clinical and imaging predictors of long-term inflammatory disease activity and disability progression in RRMS patients on natalizumab. METHODS: Patients (n = 135) were selected from our prospective observational natalizumab cohort and monitored using brain MRI and extensive clinical testing. Progression and improvement on the Expanded Disability Status Scale (EDSS), no evidence of disease activity (NEDA) and no evidence of progression or active disease (NEPAD) status were determined using measurements after the initial phase of inflammation and the early anti-inflammatory impact of natalizumab. RESULTS: EDSS progression was seen in 43.7% of patients and EDSS improvement in 17.8%. Median follow-up was 4.9 years (IQR 3.6-6.0). Patients with a longer disease duration at natalizumab initiation have a higher hazard for earlier EDSS progression (HR 1.05, CI 1.00-1.09, p = 0.037) and a higher pre-baseline relapse rate predicted a longer NEPAD status (HR 1.70, CI 1.06-2.72, p = 0.028). CONCLUSION: The results suggest that starting natalizumab early, during active inflammatory disease results in a more favourable outcome. When taking into account early inflammation and the impact of natalizumab on disease activity during the initial treatment phase, a higher than expected proportion of patients showed disability progression.


Assuntos
Fatores Imunológicos/uso terapêutico , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Natalizumab/uso terapêutico , Adulto , Avaliação da Deficiência , Progressão da Doença , Feminino , Humanos , Masculino
9.
BMC Health Serv Res ; 19(1): 436, 2019 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-31253138

RESUMO

BACKGROUND: Published literature suggests that early treatment with natalizumab ("escalation strategy") is more effective than switch within the same class of immunomodulators (interferons/glatiramer acetate, "switching strategy") in relapsing-remitting multiple sclerosis (RRMS) patients who failed first-line self-injectable disease-modifying treatment (DMT). The present analysis aims to evaluate the cost-effectiveness profile of escalation strategy vs. switching strategy, adopting the Italian societal perspective. METHODS: A lifetime horizon Markov model was developed to compare early escalation to natalizumab vs. switching among immunomodulators, followed by subsequent escalation to natalizumab. The two compared treatment algorithms were: a) early escalation until progression to Expanded Disability Status Scale (EDSS) = 7.0 vs. b) switching until EDSS = 4.0, followed by escalation until EDSS = 7.0. The model analyzed social costs, quality-adjusted survival and effects of therapies in prolonging time without disability progression and burden of relapses. Clinical data were mainly extracted from a published observational study. RESULTS: Lifetime costs of early escalation to natalizumab and switching among immunomodulators amounted to €699,700 and €718,600 per patient, respectively. Early escalation was associated with prolonged quality-adjusted survival (11.19 vs. 9.67 QALYs, + 15.8%). A slight overall survival increase was also observed (20.10 vs. 19.67 life years). Both deterministic and probabilistic sensitivity analyses confirmed the robustness of findings. CONCLUSIONS: Adopting the Italian social perspective, early escalation to natalizumab is dominant vs. switching among immunomodulators, in RRMS patients who do not respond adequately to conventional immunomodulators.


Assuntos
Fatores Imunológicos/economia , Fatores Imunológicos/uso terapêutico , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Esclerose Múltipla Recidivante-Remitente/economia , Natalizumab/economia , Natalizumab/uso terapêutico , Adulto , Análise Custo-Benefício , Progressão da Doença , Feminino , Humanos , Itália , Masculino , Cadeias de Markov , Esclerose Múltipla Recidivante-Remitente/fisiopatologia , Recidiva
10.
Zh Nevrol Psikhiatr Im S S Korsakova ; 119(2. Vyp. 2): 94-97, 2019.
Artigo em Russo | MEDLINE | ID: mdl-31156247

RESUMO

The authors consider the issues concerning planning of pregnancy in patients with multiple sclerosis receiving pathogenetic and immunomodulatory therapy and provide descriptions of cases of pregnancy in patients with aggressively multiple sclerosis occurred during the treatment with natalizumab.


Assuntos
Fatores Imunológicos , Esclerose Múltipla , Natalizumab , Complicações na Gravidez , Feminino , Humanos , Fatores Imunológicos/uso terapêutico , Imunomodulação , Esclerose Múltipla/tratamento farmacológico , Natalizumab/uso terapêutico , Gravidez , Complicações na Gravidez/tratamento farmacológico
11.
Zh Nevrol Psikhiatr Im S S Korsakova ; 119(2. Vyp. 2): 98-106, 2019.
Artigo em Russo | MEDLINE | ID: mdl-31156248

RESUMO

This paper presents a case report of subtentorial progressive multifocal leukoencephalopathy (PML) in a 26-year-old female patient treated with natalizumab. The evolution of clinical features, neuroimaging data and treatment as well as the development of immune reconstitution inflammatory syndrome (IRIS) are described. This case emphasizes the importance to keep accurately the risk management plan during natalizumab treatment. This includes performing MRI scans in order to detect changes typical for PML at the earliest (preclinical) stage in time.


Assuntos
Síndrome Inflamatória da Reconstituição Imune , Fatores Imunológicos , Leucoencefalopatia Multifocal Progressiva , Esclerose Múltipla , Natalizumab , Adulto , Anticorpos Monoclonais Humanizados , Feminino , Humanos , Fatores Imunológicos/efeitos adversos , Leucoencefalopatia Multifocal Progressiva/induzido quimicamente , Esclerose Múltipla/tratamento farmacológico , Natalizumab/efeitos adversos , Neuroimagem
13.
Continuum (Minneap Minn) ; 25(3): 689-714, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31162312

RESUMO

PURPOSE OF REVIEW: Newly introduced disease-modifying therapies offer greater efficacy than previous therapies but also have serious side effects. This article reviews factors useful in identifying those at risk of developing aggressive relapsing multiple sclerosis (MS) and therapies available for treatment. RECENT FINDINGS: Several factors predict aggressive MS, including demographic factors, relapses, symptom characteristics, MRI activity, and other biomarkers. These can be used to select patients for more aggressive therapies, including natalizumab, alemtuzumab, fingolimod, and ocrelizumab. Additional off-label treatments are available for patients with severe disease. The benefits and side effects of these treatments must be considered when making therapeutic decisions. SUMMARY: Selecting patients who are most appropriate for aggressive therapy involves considering risk factors for poor outcomes, early recognition of treatment failure, balancing treatment efficacy and side effects, and sharing the decision with patients to assist them in making optimal treatment choices. Vigilance for signs of treatment failure and early switching to more aggressive therapy are important components in optimal care.


Assuntos
Imunossupressores/administração & dosagem , Esclerose Múltipla/diagnóstico por imagem , Esclerose Múltipla/tratamento farmacológico , Neurite Óptica/diagnóstico por imagem , Neurite Óptica/tratamento farmacológico , Adulto , Fatores Etários , Alemtuzumab/administração & dosagem , Feminino , Cloridrato de Fingolimode , Acetato de Glatiramer/administração & dosagem , Humanos , Masculino , Natalizumab/administração & dosagem , Fatores Sexuais , Falha de Tratamento
14.
Continuum (Minneap Minn) ; 25(3): 715-735, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31162313

RESUMO

PURPOSE OF REVIEW: This article reviews appropriate monitoring of the various multiple sclerosis (MS) disease-modifying therapies, summarizes the reasons patients switch or stop treatment, and provides a framework for making these management decisions. RECENT FINDINGS: With the increasing number of highly effective immunotherapies available for MS, the possibility of better control of the disease has increased, but with it, the potential for side effects has rendered treatment decisions more complicated. Starting treatment early with more effective and better-tolerated disease-modifying therapies reduces the likelihood of switching because of breakthrough disease or lack of compliance. Clinical and radiographic surveillance, and often blood and other paraclinical tests, should be performed periodically, depending on the disease-modifying therapy. Helping patients navigate the uncertainty around switching or stopping treatment, either temporarily or permanently, is one of the most important things we do as providers of MS care. SUMMARY: Ongoing monitoring of drug therapy is a crucial component of long-term MS care. Switching treatments may be necessary for a variety of reasons. Permanent discontinuation of treatment may be appropriate for some patients with MS, although more study is needed in this area.


Assuntos
Monitoramento de Medicamentos/métodos , Substituição de Medicamentos/métodos , Imunossupressores/administração & dosagem , Adesão à Medicação , Esclerose Múltipla/diagnóstico por imagem , Esclerose Múltipla/tratamento farmacológico , Anticorpos Monoclonais Humanizados/administração & dosagem , Acetato de Glatiramer/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Natalizumab/administração & dosagem , Suspensão de Tratamento
15.
Continuum (Minneap Minn) ; 25(3): 773-792, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31162316

RESUMO

PURPOSE OF REVIEW: This article provides practical guidance on successful management of women with multiple sclerosis (MS) through pregnancy and the postpartum period. RECENT FINDINGS: Recent studies indicate that most women diagnosed with MS today can have children, breast-feed, and resume beta interferons or glatiramer acetate per their preferences without incurring an increased risk of relapses during the postpartum period. More than 40% of women with mild MS do not require any treatment before conception or in the postpartum period. Women with highly active MS can now become well-controlled before, throughout, and after pregnancy via highly effective treatments. Unfortunately, pregnancy does not protect against relapses following the cessation of fingolimod or natalizumab, and some women experience severe rebound relapses during pregnancy. Accidental first-trimester exposure to teriflunomide or fingolimod increases the risk of fetal harm. SUMMARY: Most women with MS can have normal pregnancies and breast-feed without incurring harm. Clinicians should avoid prescribing medications with known teratogenic potential (teriflunomide, fingolimod), known risk of severe rebound relapses (fingolimod, natalizumab), or unclear but plausible risks (dimethyl fumarate, alemtuzumab) to women of childbearing age who desire pregnancy or are not on reliable birth control. If a treatment needs to be resumed during breast-feeding, clinicians should opt for glatiramer acetate, interferon beta, natalizumab, or rituximab/ocrelizumab, as biologically plausible risks to the infant are exceedingly low.


Assuntos
Aleitamento Materno , Fatores Imunológicos/administração & dosagem , Esclerose Múltipla/diagnóstico por imagem , Esclerose Múltipla/tratamento farmacológico , Complicações na Gravidez/diagnóstico por imagem , Complicações na Gravidez/tratamento farmacológico , Adulto , Aleitamento Materno/tendências , Serviços de Planejamento Familiar/tendências , Feminino , Acetato de Glatiramer/administração & dosagem , Humanos , Interferon beta/administração & dosagem , Esclerose Múltipla Recidivante-Remitente/diagnóstico por imagem , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Natalizumab/administração & dosagem , Gravidez , Adulto Jovem
16.
Mol Med Rep ; 20(1): 678-684, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31180553

RESUMO

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system of autoimmune etiopathogenesis, and is characterized by various neurological symptoms. Glatiramer acetate and interferon­ß are administered as first­line treatments for this disease. In non­responsive patients, several second­line therapies are available, including natalizumab; however, a percentage of MS patients does not respond, or respond partially. Therefore, it is of the utmost importance to develop a diagnostic test for the prediction of drug response in patients suffering from complex diseases, such as MS, where several therapeutic options are already available. By a machine learning approach, the UnCorrelated Shrunken Centroid algorithm was applied to identify a subset of genes of CD4+ T cells that may predict the pharmacological response of relapsing­remitting MS patients to natalizumab, before the initiation of therapy. The results from the present study may provide a basis for the design of personalized therapeutic strategies for patients with MS.


Assuntos
Linfócitos T CD4-Positivos/efeitos dos fármacos , Fatores Imunológicos/uso terapêutico , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Natalizumab/uso terapêutico , Biomarcadores Farmacológicos/análise , Linfócitos T CD4-Positivos/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Aprendizado de Máquina , Esclerose Múltipla Recidivante-Remitente/diagnóstico , Esclerose Múltipla Recidivante-Remitente/genética , Prognóstico , Transcriptoma/efeitos dos fármacos
17.
Mult Scler Relat Disord ; 33: 146-152, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31200271

RESUMO

BACKGROUND: Both natalizumab and fingolimod are highly effective in the treatment of relapsing-remitting MS (RRMS). In the absence of head-to-head trials, some observational studies have compared their efficacy with conflicting results. OBJECTIVES: To investigate the efficacy of natalizumab and fingolimod in a cohort of RRMS patients in an observational, retrospective study. METHODS: We included all consecutive RRMS patients who started natalizumab or fingolimod in three MS centres with a follow-up to 24 months and analysed clinical and brain MRI data after propensity score (PS) matching. RESULTS: After 1:1 PS-matching, we retained 102 patients in both groups, with similar baseline features. After 24 months, although both drugs resulted highly effective, patients treated with natalizumab had a lower relapse risk (HR 0.59 CI 95% 0.35-1.00, p = 0.048) and higher time to first relapse. MRI-combined-unique-activity was found in 31.8% of natalizumab vs 43.2% of fingolimod treated patients (p = 0.28). We found a higher proportion of patients with confirmed regression of disability (19.2 vs 6.7%, p = 0.03) and 2-year no evidence of disease activity (NEDA-3, 39.0% vs 22.0%, p = 0.04) in the natalizumab group. CONCLUSIONS: Both drugs were highly effective in our cohort. Natalizumab proved superior in inducing regression of disability and 2-year-NEDA-3.


Assuntos
Cloridrato de Fingolimode/uso terapêutico , Fatores Imunológicos/uso terapêutico , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Natalizumab/uso terapêutico , Adulto , Feminino , Humanos , Itália , Masculino , Estudos Retrospectivos
18.
PLoS One ; 14(5): e0217208, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31141529

RESUMO

Multiple sclerosis (MS) treatment options have improved significantly over the past decades, but the consequences of MS can still be devastating and the needs for monitoring treatment surveillance are considerable. In the current study we used affinity proteomics technology to identify potential biomarkers which could ultimately be used to as facilitate treatment decisions. We profiled the intra-individual changes in the levels of 59 target proteins using an antibody suspension bead array in serial plasma samples from 44 MS patients during treatment with natalizumab followed by fingolimod. Nine proteins showed decreasing plasma levels during natalizumab treatment, with PEBP1 and RTN3 displaying the most significant changes. Protein levels remained stable during fingolimod treatment for both proteins. The decreasing PEBP1 levels during natalizumab treatment could be validated using ELISA and replicated in an independent cohort. These results support the use of this technology as a high throughput method of identifying potentially useful biomarkers of MS treatment.


Assuntos
Biomarcadores/sangue , Cloridrato de Fingolimode/uso terapêutico , Fatores Imunológicos/uso terapêutico , Imunossupressores/uso terapêutico , Esclerose Múltipla/sangue , Natalizumab/uso terapêutico , Adulto , Estudos de Coortes , Feminino , Humanos , Masculino , Esclerose Múltipla/tratamento farmacológico , Esclerose Múltipla/imunologia , Proteômica
20.
Gut ; 68(9): 1688-1700, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31127023

RESUMO

Intestinal immune cell trafficking has been identified as a central event in the pathogenesis of inflammatory bowel diseases (IBD). Intensive research on different aspects of the immune mechanisms controlling and controlled by T cell trafficking and retention has led to the approval of the anti-α4ß7 antibody vedolizumab, the ongoing development of a number of further anti-trafficking agents (ATAs) such as the anti-ß7 antibody etrolizumab or the anti-MAdCAM-1 antibody ontamalimab and the identification of potential future targets like G-protein coupled receptor 15. However, several aspects of the biology of immune cell trafficking and regarding the mechanism of action of ATAs are still unclear, for example, which impact these compounds have on the trafficking of non-lymphocyte populations like monocytes and how precisely these therapies differ with regard to their effect on immune cell subpopulations. This review will summarise recent advances of basic science in the field of intestinal immune cell trafficking and discuss these findings with regard to different pharmacological approaches from a translational perspective.


Assuntos
Fármacos Gastrointestinais/uso terapêutico , Doenças Inflamatórias Intestinais/imunologia , Linfócitos T/imunologia , Anticorpos Monoclonais/farmacologia , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados , Adesão Celular/efeitos dos fármacos , Adesão Celular/imunologia , Quimiotaxia de Leucócito/efeitos dos fármacos , Quimiotaxia de Leucócito/imunologia , Fármacos Gastrointestinais/farmacologia , Humanos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Mucosa Intestinal/imunologia , Terapia de Alvo Molecular/métodos , Natalizumab/farmacologia , Natalizumab/uso terapêutico , Oligonucleotídeos Fosforotioatos/farmacologia , Oligonucleotídeos Fosforotioatos/uso terapêutico
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA