RESUMO
BACKGROUND: Psoriatic arthritis (PsA) is a chronic inflammatory disease that affects multiple joints. It is associated with psoriasis and treated with synthetic and biologic drugs. OBJECTIVE: The objective of this study was to assess the outcomes of patients who received biologic therapy with tumor necrosis factor (TNF) inhibitors in terms of effectiveness, safety, functionality, and quality of life. DESIGN AND SETTING: A prospective observational study was performed at a single center in Belo Horizonte, Brazil. METHODS: Patients with PsA who received their first TNF inhibitor treatment were followed up for 12 months. Disease activity was measured using the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Clinical Disease Activity Index (CDAI). Functionality was measured using the Health Questionnaire Assessment (HAQ), and quality of life was evaluated using the European Quality of Life Five Dimensions (EQ-5D). Multiple linear regression was used to identify predictors of the clinical response at 12 months. RESULTS: A total of 143 patients treated with adalimumab or etanercept were evaluated. Most of the clinical measures were significantly improved at 12 months. However, 31%-51% of the patients did not achieve good clinical control. No differences were observed between adalimumab and etanercept, except for poor functionality at 12 months among patients treated with etanercept. The main predictors of a worse clinical response were female sex, etanercept use, poor functionality, or lower quality of life at baseline. The main adverse reactions were alopecia, headache, injection site reaction, sinusitis, flu, dyslipidemia, and infections. CONCLUSION: TNF inhibitor therapy was effective and safe. However, despite improvements in clinical measures, most patients did not achieve satisfactory control of the disease.
Assuntos
Antirreumáticos , Artrite Psoriásica , Humanos , Feminino , Masculino , Artrite Psoriásica/tratamento farmacológico , Artrite Psoriásica/induzido quimicamente , Etanercepte/uso terapêutico , Adalimumab/uso terapêutico , Inibidores do Fator de Necrose Tumoral , Antirreumáticos/uso terapêutico , Receptores do Fator de Necrose Tumoral/uso terapêutico , Infliximab/uso terapêutico , Qualidade de Vida , Anticorpos Monoclonais/uso terapêutico , Fator de Necrose Tumoral alfa , Imunoglobulina G , Resultado do TratamentoRESUMO
OBJECTIVE: To compare the clinical response at 24 months and evaluate the adverse events (AEs) of patients with rheumatoid arthritis (RA) treated with etanercept 50 (injectable solution 50 mg prefilled syringe), etanercept 25 (lyophilized 25 mg), infliximab, adalimumab, or golimumab. METHODS: A cohort study was carried out in patients with RA, in treatment with etanercept (injectable solution 50 mg prefilled syringe or lyophilized 25 mg), infliximab, adalimumab, or golimumab. Duration of study: follow-up was carried out for 24 months. The difference of initial and final 28-joint Disease Activity Score, remission incidence, difference of initial and final Health Assessment Questionnaire score, disability recovery, and AE rate were evaluated. RESULTS: The study enrolled 435 patients (108 adalimumab, 107 infliximab, 92 etanercept 25 mg, 81 etanercept 50 mg, and 47 golimumab). For etanercept 50, the median difference between basal and at the end of follow-up 28-joint Disease Activity Score was 1.7. For golimumab, it was 1.4; for adalimumab, it was 1.1; for etanercept 25, it was 1.02; and for infliximab, it was 0.96 (p = 0.001). The median difference between basal and final Health Assessment Questionnaire ranged was 1.66 for etanercept 50, 1.34 for etanercept 25, 1.3 for golimumab, 1.24 for adalimumab, and 1.07 for infliximab (p = 0.0005). Comparatively, etanercept 50 presented the highest cumulative incidence (77%; 95% confidence interval [CI], 67%-86%) and remission incidence (64 cases per 100 person-months; 95% CI, 4.9-8.1 cases per 100 person-months) and the lowest AE rate (8.6 per 100 person-years; 95% CI, 5.3-15 per 100 person-years). CONCLUSIONS: In patients with RA treated with anti-tumor necrosis factor α drugs, the highest incidence of remission and the lowest rate of AEs were documented for the cohort exposed to etanercept 50 mg.
Assuntos
Antirreumáticos , Artrite Reumatoide , Preparações Farmacêuticas , Adalimumab/efeitos adversos , Anticorpos Monoclonais Humanizados/uso terapêutico , Antirreumáticos/efeitos adversos , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/epidemiologia , Estudos de Coortes , Colômbia/epidemiologia , Etanercepte/efeitos adversos , Humanos , Imunoglobulina G , Infliximab/efeitos adversos , Receptores do Fator de Necrose Tumoral/uso terapêutico , Resultado do TratamentoRESUMO
OBJECTIVES: To assess the incidence of tuberculosis and to screen for latent tuberculosis infection among Brazilians with rheumatoid arthritis using biologics in clinical practice. PATIENTS AND METHODS: This cohort study used data from the Brazilian Registry of Biological Therapies in Rheumatic Diseases (Registro Brasileiro de Monitoração de Terapias Biológicas - BiobadaBrasil), from 01/2009 to 05/2013, encompassing 1552 treatments, including 415 with only synthetic disease-modifying anti-rheumatic drugs, 942 synthetic DMARDs combined with anti-tumor necrosis factor (etanercept, infliximab, adalimumab) and 195 synthetic DMARDs combined with other biologics (abatacept, rituximab and tocilizumab). The occurrence of tuberculosis and the drug exposure time were assessed, and screening for tuberculosis was performed. STATISTICAL ANALYSIS: Unpaired t-test and Fisher's two-tailed test; p<0.05. RESULTS: The exposure times were 981 patient-years in the controls, 1744 patient-years in the anti-TNF group (adalimumab=676, infliximab=547 and etanercept=521 patient-years) and 336 patient-years in the other biologics group. The incidence rates of tuberculosis were 1.01/1000 patient-years in the controls and 2.87 patient-years among anti-TNF users (adalimumab=4.43/1000 patient-years; etanercept=1.92/1000 patient-years and infliximab=1.82/1000 patient-years). No cases of tuberculosis occurred in the other biologics group. The mean drug exposure time until the occurrence of tuberculosis was 27(11) months for the anti-TNF group. CONCLUSIONS: The incidence of tuberculosis was higher among users of synthetic DMARDs and anti-TNF than among users of synthetic DMARDs and synthetic DMARDs and non-anti-TNF biologics and also occurred later, suggesting infection during treatment and no screening failure.
Assuntos
Artrite Reumatoide/tratamento farmacológico , Fatores Biológicos/uso terapêutico , Receptores do Fator de Necrose Tumoral/uso terapêutico , Tuberculose/induzido quimicamente , Fator de Necrose Tumoral alfa/uso terapêutico , Adalimumab/uso terapêutico , Brasil/epidemiologia , Estudos de Casos e Controles , Estudos de Coortes , Etanercepte/uso terapêutico , Incidência , Infliximab/uso terapêutico , Sistema de Registros , Tuberculose/epidemiologia , Fator de Necrose Tumoral alfa/antagonistas & inibidoresRESUMO
INTRODUCCIÓN: El Linfoma de Hodgkin (LH) representa aproximadamente el 30% de todos los linfomas. Es altamente curable con una supervivencia a los 5 años por encima del 85%, que es incluso mayor en los pacientes en etapa temprana de la enfermedad. A pesar de una buena respuesta inicial al tratamiento, aproximadamente del 20% al 30% de los pacientes recaerán y requerirán terapia de rescate. La terapia de los pacientes con recaída o refractarios al tratamiento con buena performance consiste en una terapia de dosis alta de quimioterapia de rescate y trasplante autólogo de medula ósea (TAMO). A pesar de que el TAMO puede ser curativo, será ineficaz hasta en un 50% de los pacientes Para los pacientes con peor performance el TAMO no es un opción terapéutica. Para estos pacientes o los que recaen después de un trasplante de células madre se necesitan nuevas terapias efectivas. En esta etapa tardía de la enfermedad, la expectativa de vida es corta, y las pocas opciones de tratamiento se asocian con una alta morbilidad. Brentuximab vedotin representa la primera terapia aprobada dirigida contra el antígeno expresado en la superficie celular CD30 en las células de LH y en otros tumores hematológicos como linfoma de células grandes anaplásico sistémico (LCGAs). ALCANCE Y OBJETIVO: Efectuar una revisión rápida de la evidencia disponible sobre el uso de Brentuximab vedotin en pacientes con diagnostico de Linfoma de Hodgkin recaído refractario luego de terapia previa (incluido TAMO), como actualización de la revisión publicada en el año 2013. TECNOLOGÍA: El Brentuximab Vedotin identifica el receptor del factor de necrosis tumoral CD30, que se expresa en la superficie de las células del LCGAs y del LH. El Brentuximab Vedotin está compuesto del anticuerpo monoclonal específico de CD30 cAC10 y del fármaco antitubulina monometil auristatin E, que son ligados por un conector hendible a la proteasa. El fármaco con anticuerpos conjugados se une a CD30 en la superficie de las células del linfoma y se internaliza rápidamente. Dentro de la célula, el conector es hendido de manera selectiva y el monometil auristatin E se une a la tubulina y así provoca la interrupción del ciclo celular y la apoptosis. METODOLOGÍA: Se realizó una búsqueda electrónica de publicaciones dirigida a los idiomas inglés y español. La franja de tiempo para la búsqueda fue entre 01/2013 hasta 01/2017 inclusive. Los tipos de estudios buscados fueron ensayos clínicos randomizados, revisiones sistemáticas, metanálisis y estudios de costo- efectividad. La búsqueda se llevó a cabo en las siguientes bases: PubMed, Tripdatabase; búsquedas manuales en NICE, AHR, SIGN, SMC, HTA de NIHR, CIGNA, AETNA así como en google. Se realizó una búsqueda bibliográfica sistemática en forma independiente por distintos miembros del Instituto Nacional del Cáncer. Se consultaron fuentes primarias (trabajos randomizados y controlados) y secundarias (Revisiones sistemáticas y metanálisis realizados bajo una metodología clara, evaluaciones de tecnologías sanitarias y estudios fármaco-económicos). Se sintetizó dicha información y se la analizó. CONCLUSIONES: En esta actualización se resume un ECA fase 3 que evalúa la eficacia de Brentuximab vedotin como terapia de consolidación post TAMO. Incluyo 329 pacientes diagnosticados con LH RR de alto riesgo de recaída, y se demuestra un beneficio ES con el tratamiento con Brentuximab comparado con placebo en SLP (HR 0,57 p=0,0013 y mediana 42,9 meses vs 24,1 meses) sin demostrar beneficios en SVG. El perfil de toxicidad fue similar a los reportados en ensayos previos. Dos revisiones sistemáticas reúnen: 480 pacientes pertenecientes al programa de acceso expandido, reportando una TRO 58-80%, SV a 1 año 67-76% y a 2 años 58-67% y 903 pacientes con una TRO mediana de 62,7% , SLP a 1 año 47,6% y SVG al año 79%. Ambas revisiones tienen la limitación de reportar datos retrospectivos con una heterogeneidad en la población significativa. Un metanálisis incluye 2619 pacientes utilizando los datos provenientes del ensayo pivotal fase 2 vs el tratamiento con quimioterapia, trasplante alogenico y otras terapias. Nuevamente la principal limitación es que consiste en una comparación indirecta de ensayos de una sola rama, con población heterogénea y realizada de forma retrospectiva, en donde algunos ensayos reportaron datos inmaduros de eficacia. No obstante, demuestran en el análisis de datos conjunto una mejora ES en la SVG: tomando en cuenta los pacientes que se trataron previamente con TAMO, la mediana fue 28 meses, mayor que la de los pacientes que recibieron otros tratamientos. En diferentes guías de práctica clínica, basándose en evidencia limitada surge la recomendación de Brentuximab vedotin como una alternativa de tratamiento.
Assuntos
Humanos , Doença de Hodgkin/tratamento farmacológico , Receptores do Fator de Necrose Tumoral/uso terapêutico , Avaliação da Tecnologia Biomédica , Análise Custo-EficiênciaRESUMO
Abstract Objectives To assess the incidence of tuberculosis and to screen for latent tuberculosis infection among Brazilians with rheumatoid arthritis using biologics in clinical practice. Patients and methods This cohort study used data from the Brazilian Registry of Biological Therapies in Rheumatic Diseases (Registro Brasileiro de Monitoração de Terapias Biológicas - BiobadaBrasil), from 01/2009 to 05/2013, encompassing 1552 treatments, including 415 with only synthetic disease-modifying anti-rheumatic drugs, 942 synthetic DMARDs combined with anti-tumor necrosis factor (etanercept, infliximab, adalimumab) and 195 synthetic DMARDs combined with other biologics (abatacept, rituximab and tocilizumab). The occurrence of tuberculosis and the drug exposure time were assessed, and screening for tuberculosis was performed. Statistical analysis: Unpaired t-test and Fisher's two-tailed test; p < 0.05. Results The exposure times were 981 patient-years in the controls, 1744 patient-years in the anti-TNF group (adalimumab = 676, infliximab = 547 and etanercept = 521 patient-years) and 336 patient-years in the other biologics group. The incidence rates of tuberculosis were 1.01/1000 patient-years in the controls and 2.87 patient-years among anti-TNF users (adalimumab = 4.43/1000 patient-years; etanercept = 1.92/1000 patient-years and infliximab = 1.82/1000 patient-years). No cases of tuberculosis occurred in the other biologics group. The mean drug exposure time until the occurrence of tuberculosis was 27(11) months for the anti-TNF group. Conclusions The incidence of tuberculosis was higher among users of synthetic DMARDs and anti-TNF than among users of synthetic DMARDs and synthetic DMARDs and non-anti-TNF biologics and also occurred later, suggesting infection during treatment and no screening failure.
Resumo Objetivos Avaliar incidência de tuberculose e triagem para tuberculose latente em brasileiros com artrite reumatoide em uso de agentes biológicos na prática clinica. Pacientes e métodos Estudo de coorte com dados do Registro Brasileiro de Monitoração de Terapias Biológicas (BiobadaBrasil), de 01/2009 a 05/2013, abrangeu 1.552 tratamentos, 415 somente com drogas modificadoras do curso da doença (MMCDs) sintéticas, 942 MMCDs sintéticas em associação com anti-TNF (etanercepte, infliximabe, adalimumabe) e 195 MMCDs sintéticas em associação com outros biológicos (abatacepte, rituximabe e tocilizumabe). Avaliaram-se ocorrência de tuberculose, tempo de exposição às drogas e triagem para TB. Análise estatística: teste t não pareado e teste de Fisher bicaudal; p < 0,05. Resultados O tempo de exposição dos controles foi de 981 pacientes-ano, do grupo de anti-TNF foi de 1.744 pacientes-ano (adalimumabe = 676, infliximabe = 547 e etanercepte = 521 pacientes-ano) e o de outros biológicos de 336 pacientes-ano. A incidência de TB foi de 1,01/1.000 pacientes-ano nos controles e de 2,87 pacientes-ano nos usuários de anti-TNF (adalimumabe = 4,43/1.000 pacientes-ano; etanercepte = 1,92/1.000 pacientes-ano e infliximabe = 1,82/1.000 pacientes-ano). Não houve casos de tuberculose no grupo de outros biológicos. O tempo médio de exposição até a ocorrência de tuberculose foi de 27(11) meses para o grupo anti-TNF. Conclusões A incidência de tuberculose foi maior nos usuários de MMCDs sintéticas e anti-TNF do que nos usuários de MMCDs sintéticas e de MMCDs sintéticas e biológicos não anti-TNF, e também mais tardia, sugerindo infecção durante o tratamento, e não falha na triagem.
Assuntos
Artrite Reumatoide/tratamento farmacológico , Tuberculose/induzido quimicamente , Fatores Biológicos/uso terapêutico , Fator de Necrose Tumoral alfa/uso terapêutico , Receptores do Fator de Necrose Tumoral/uso terapêutico , Tuberculose/epidemiologia , Brasil/epidemiologia , Estudos de Casos e Controles , Sistema de Registros , Incidência , Estudos de Coortes , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adalimumab/uso terapêutico , Infliximab/uso terapêutico , Etanercepte/uso terapêuticoRESUMO
INTRODUCTION: Patients with ankylosing spondylitis require a team approach from multiple professionals, various treatment modalities for continuous periods of time, and can lead to the loss of labour capacity in a young population. So, it is necessary to measure its socio-economic impact. OBJECTIVES: To describe the use of public resources to treat AS in a tertiary hospital after the use of biological medications was approved for treating spondyloarthritis in the Health Public System, establishing approximate values for the direct and indirect costs of treating this illness in Brazil. MATERIAL AND METHODS: 93 patients selected from the ambulatory spondyloarthritis clinic at the Hospital de Clínicas of the Federal University of Paraná between September 2011 and September 2012 had their direct costs indirect treatment costs estimation. RESULTS: 70 patients (75.28%) were male and 23 (24.72%) female. The mean age was 43.95 years. The disease duration was calculated based on the age of diagnosis and the mean was 8.92 years (standard deviation: 7.32); 63.44% were using anti-tumour necrotic factor drugs. Comparing male and female patients the mean Bath Ankylosing Spondylitis Disease Activity Index was 4.64 and 5.49 while the mean Bath Ankylosing Spondylitis Functional Index was 5.03 and 6.35 respectively. CONCLUSIONS: The Brazilian public health system's spending related to ankylosing spondylitis has increased in recent years. An important part of these costs is due to the introduction of new, more expensive health technologies, as in the case of nuclear magnetic resonance and, mainly, the incorporation of anti-tumour necrotic factor therapy into the therapeutic arsenal. The mean annual direct and indirect cost to the Brazilian public health system to treat a patient with ankylosing spondylitis, according to our findings, is US$ 23,183.56.
Assuntos
Custos de Cuidados de Saúde , Espondilite Anquilosante/tratamento farmacológico , Espondilite Anquilosante/economia , Adulto , Brasil , Custos e Análise de Custo , Feminino , Humanos , Masculino , Saúde Pública , Receptores do Fator de Necrose Tumoral/uso terapêutico , Índice de Gravidade de Doença , Fator de Necrose Tumoral alfa/antagonistas & inibidoresRESUMO
ABSTRACT Introduction: Patients with Ankylosing Spondylitis (AS) require a team approach from multiple professionals, various treatment modalities for continuous periods of time, and can lead to the loss of labour capacity in a young population. So, it is necessary to measure its socio-economic impact. Objectives: To describe the use of public resources to treat AS in a tertiary hospital after the use of biological medications was approved for treating spondyloarthritis in the Health Public System, establishing approximate values for the direct and indirect costs of treating this illness in Brazil. Material and methods: 93 patients selected from the ambulatory spondyloarthritis clinic at the Hospital de Clínicas of the Federal University of Paraná between September 2011 and September 2012 had their direct costs indirect treatment costs estimation. Results: 70 patients (75.28%) were male and 23 (24.72%) female. The mean age was 43.95 years. The disease duration was calculated based on the age of diagnosis and the mean was 8.92 years (standard deviation: 7.32); 63.44% were using anti-TNF drugs. Comparing male and female patients the mean BASDAI was 4.64 and 5.49 while the mean BASFI was 5.03 and 6.35 respectively. Conclusions: The Brazilian public health system's spending related to ankylosing spondylitis has increased in recent years. An important part of these costs is due to the introduction of new, more expensive health technologies, as in the case of nuclear magnetic resonance and, mainly, the incorporation of anti-TNF therapy into the therapeutic arsenal. The mean annual direct and indirect cost to the Brazilian public health system to treat a patient with ankylosing spondylitis, according to our findings, is US$ 23,183.56.
RESUMO Introdução: Os pacientes com espondilite anquilosante (EA) exigem uma abordagem de equipe com vários profissionais e várias modalidades de tratamento, continuamente; além disso, a doença pode levar à perda da capacidade de trabalho em uma população jovem, de modo que é necessário medir o seu impacto socioeconômico. Objetivos: Descrever o uso de recursos públicos para o tratamento da EA em um hospital terciário após o uso dos fármacos biológicos ter sido aprovado para o tratamento das espondiloartrites pelo Sistema Público de Saúde e estabelecer valores aproximados para os custos diretos e indiretos do tratamento dessa doença no Brasil. Material e métodos: Foram estimados os custos de tratamento diretos e indiretos de 93 pacientes com EA do ambulatório de espondiloartrite do Hospital de Clínicas da Universidade Federal do Paraná, entre setembro de 2011 e setembro 2012. Resultados: Dos pacientes, 70 (75,28%) eram do sexo masculino e 23 (24,72%) do feminino. A idade média foi de 43,95 anos. A duração da doença foi calculada com base na idade do diagnóstico e a média foi de 8,92 anos (desvio padrão: 7,32); 63,44% dos indivíduos usavam fármacos anti-TNF. Na comparação dos pacientes dos sexos masculino e feminino, a média no Bath Ankylosing Spondylitis Disease Activity Index (Basdai) foi de 4,64 e 5,49, enquanto a média no Bath Ankylosing Spondylitis Functional Index (Basfi) foi de 5,03 e 6,35, respectivamente. Conclusões: Os gastos do sistema público de saúde brasileiro relacionados com a espondilite anquilosante aumentaram nos últimos anos. Uma parte importante desses custos deve-se à introdução das novas tecnologias de saúde, mais dispendiosas, como no caso da ressonância nuclear magnética e, principalmente, da incorporação da terapia anti-TNF ao arsenal terapêutico. O custo médio anual direto e indireto do sistema público de saúde brasileiro para tratar de um paciente com espondilite anquilosante, de acordo com os resultados deste estudo, é de US$ 23.183,56.
Assuntos
Humanos , Masculino , Feminino , Adulto , Espondilite Anquilosante/economia , Espondilite Anquilosante/tratamento farmacológico , Custos de Cuidados de Saúde , Índice de Gravidade de Doença , Brasil , Saúde Pública , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Receptores do Fator de Necrose Tumoral/uso terapêutico , Custos e Análise de CustoRESUMO
BACKGROUND: Angiogenesis is an early stage of psoriatic lesion development, but less is known about lymphagiogenesis and its role in the development of psoriasis. OBJECTIVE: To examine the expression of specific lymphatic markers and lymphatic growth factors in untreated psoriatic skin, in the unaffected skin of patients and skin of healthy volunteers, as well as their alteration after treatment with an anti-TNF agent. METHODS: Immunohistochemistry for the lymphatic markers D2-40 and LYVE-1, in addition to the VEGF-C and VEGF-D growth factors, was performed in the skin biopsies of psoriatic lesions and adjacent non-psoriatic skin of 19 patients before and after treatment with etanercept, as well as in the skin biopsies of 10 healthy volunteers. RESULTS: The expressions of D2-40, VEGF-C and VEGF-D on lymphatic vessels underwent statistically significant increases in untreated psoriatic skin compared with non-lesional skin, in contrast to LYVE-1, which did not involve significant increase in expression in psoriatic skin. VEGF-C expression on lymphatic vessels diminished after treatment with etanercept. Moreover VEGF-C and VEGF-D staining on fibroblasts presented with higher expression in lesional skin than in non-lesional adjacent skin. CONCLUSION: Remodeling of lymphatic vessels possibly occurs during psoriatic lesion development, parallel to blood vessel formation. The exact role of this alteration is not yet clear and more studies are necessary to confirm these results. .
Assuntos
Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Anticorpos Monoclonais Murinos/análise , Vasos Linfáticos/patologia , Psoríase/tratamento farmacológico , Fatores de Necrose Tumoral/antagonistas & inibidores , Fatores de Crescimento do Endotélio Vascular/análise , Proteínas de Transporte Vesicular/análise , Anticorpos Monoclonais Murinos/efeitos dos fármacos , Biópsia , Biomarcadores/análise , Imuno-Histoquímica , Imunoglobulina G/uso terapêutico , Fatores Imunológicos/uso terapêutico , Linfangiogênese/efeitos dos fármacos , Vasos Linfáticos/efeitos dos fármacos , Psoríase/metabolismo , Psoríase/patologia , Valores de Referência , Receptores do Fator de Necrose Tumoral/uso terapêutico , Estatísticas não Paramétricas , Pele/efeitos dos fármacos , Pele/patologia , Fatores de Crescimento do Endotélio Vascular/efeitos dos fármacos , Proteínas de Transporte Vesicular/efeitos dos fármacosRESUMO
BACKGROUND: Angiogenesis is an early stage of psoriatic lesion development, but less is known about lymphagiogenesis and its role in the development of psoriasis. OBJECTIVE: To examine the expression of specific lymphatic markers and lymphatic growth factors in untreated psoriatic skin, in the unaffected skin of patients and skin of healthy volunteers, as well as their alteration after treatment with an anti-TNF agent. METHODS: Immunohistochemistry for the lymphatic markers D2-40 and LYVE-1, in addition to the VEGF-C and VEGF-D growth factors, was performed in the skin biopsies of psoriatic lesions and adjacent non-psoriatic skin of 19 patients before and after treatment with etanercept, as well as in the skin biopsies of 10 healthy volunteers. RESULTS: The expressions of D2-40, VEGF-C and VEGF-D on lymphatic vessels underwent statistically significant increases in untreated psoriatic skin compared with non-lesional skin, in contrast to LYVE-1, which did not involve significant increase in expression in psoriatic skin. VEGF-C expression on lymphatic vessels diminished after treatment with etanercept. Moreover VEGF-C and VEGF-D staining on fibroblasts presented with higher expression in lesional skin than in non-lesional adjacent skin. CONCLUSION: Remodeling of lymphatic vessels possibly occurs during psoriatic lesion development, parallel to blood vessel formation. The exact role of this alteration is not yet clear and more studies are necessary to confirm these results.
Assuntos
Anticorpos Monoclonais Murinos/análise , Vasos Linfáticos/patologia , Psoríase/tratamento farmacológico , Inibidores do Fator de Necrose Tumoral , Fatores de Crescimento do Endotélio Vascular/análise , Proteínas de Transporte Vesicular/análise , Adulto , Anticorpos Monoclonais Murinos/efeitos dos fármacos , Biomarcadores/análise , Biópsia , Etanercepte , Feminino , Humanos , Imunoglobulina G/uso terapêutico , Imuno-Histoquímica , Fatores Imunológicos/uso terapêutico , Linfangiogênese/efeitos dos fármacos , Vasos Linfáticos/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Psoríase/metabolismo , Psoríase/patologia , Receptores do Fator de Necrose Tumoral/uso terapêutico , Valores de Referência , Pele/efeitos dos fármacos , Pele/patologia , Estatísticas não Paramétricas , Fatores de Crescimento do Endotélio Vascular/efeitos dos fármacos , Proteínas de Transporte Vesicular/efeitos dos fármacosRESUMO
OBJECTIVE: To compare the modifications in lipids between patients with rheumatoid arthritis (RA) receiving etanercept plus methotrexate (ETA + MTX) versus methotrexate (MTX) and their relationship with serum levels of tumor necrosis factor-alpha (TNF-α). METHODS: In an observational cohort study, we compared changes in lipid levels in patients receiving ETA + MTX versus MTX in RA. These groups were assessed at baseline and at 4 and 24 weeks, measuring clinical outcomes, total cholesterol, triglycerides, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol, and TNF-α. RESULTS: Baseline values for lipid levels were similar in both groups. HDL-C levels increased significantly only in the ETA + MTX group (from 45.5 to 50.0 mg/dL at 4 weeks, a 10.2% increase, P < 0.001, and to 56.0 mg/dL at 24 weeks, a 25.1% increase, P < 0.001), while other lipids underwent no significant changes. ETA + MTX also exhibited a significant increase in TNF-α (44.8 pg/mL at baseline versus 281.4 pg/mL at 24 weeks, P < 0.001). The MTX group had no significant changes in lipids or TNF-α. Significant differences in HDL-C between groups were observed at 24 weeks (P = 0.04) and also in TNF-α (P = 0.01). CONCLUSION: HDL-C levels increased significantly following treatment with ETA + MTX, without a relationship with decrease of TNF-α.