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1.
Acta Derm Venereol ; 98(7): 648-654, 2018 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-29405245

RESUMO

Interleukin 17-antagonist secukinumab demonstrated high efficacy for treatment of psoriasis in randomized controlled trials. However, performance in daily practice may differ from trials. Drug survival is a comprehensive outcome covering effectiveness and safety, suitable for analyses of daily practice. The aim of this study was to evaluate drug survival of secukinumab in a daily practice psoriasis cohort. Data were collected from 13 hospitals. Drug survival was analysed using Kaplan-Meier survival curves, split for reason of discontinuation. In total, 196 patients were included (83% biologic experienced). Overall, 12 and 18 months drug survival of secukinumab was 76% and 67%, respectively, and was mostly determined by ineffectiveness. There was a trend towards shorter drug survival in women and in biologic experienced patients. Thirteen percent of patients experienced at least one episode of fungal infection. This is one of the first studies of drug survival of secukinumab in patients with psoriasis treated in daily practice.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Fármacos Dermatológicos/uso terapêutico , Psoríase/tratamento farmacológico , Adulto , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais Humanizados , Fármacos Dermatológicos/efeitos adversos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Países Baixos , Modelos de Riscos Proporcionais , Psoríase/diagnóstico , Psoríase/imunologia , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento
2.
Dermatology ; 225(4): 298-303, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23257348

RESUMO

BACKGROUND: There is a need for biomarkers to screen the effectiveness of (novel) therapeutic agents for psoriasis at an early stage. OBJECTIVE: We aimed to determine which of the changes in psoriatic skin correlates best with clinical improvement 4 weeks after effective adalimumab therapy. METHODS: Twenty-two psoriatic arthritis patients were randomized to receive adalimumab or placebo. T cell numbers and markers of innate immunity were estimated in lesional and nonlesional skin biopsies at baseline and after 4 weeks of treatment. RESULTS: CD161+ and elastase+ dermal cells in lesional skin were significantly reduced upon 4 weeks of successful adalimumab treatment compared with placebo. CONCLUSION: Early improvement of psoriasis lesions during adalimumab therapy is associated with a marked reduction of infiltrated dermal CD161+ T cells and elastase+ neutrophils, suggesting that these parameters could be used as biomarkers to monitor early changes after active treatment in small proof-of-concept studies of short duration.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Antirreumáticos/uso terapêutico , Artrite Psoriásica/tratamento farmacológico , Psoríase/tratamento farmacológico , Pele/efeitos dos fármacos , Adalimumab , Adulto , Idoso , Artrite Psoriásica/metabolismo , Biomarcadores/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Psoríase/metabolismo , Linfócitos T/metabolismo , Adulto Jovem
3.
Arch Dermatol Res ; 304(6): 443-9, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22438166

RESUMO

There is limited information available regarding the phenotype and function of leukocytes involved in the earliest stages of psoriatic lesion development. In this study, we examined the presence of different types of leukocytes in psoriatic point lesions collected at three 1-week interval time points from a recent and simultaneously formed group of point lesions. The cells were quantified and compared with K16 expression and epidermal thickness, both typically increased in this disease and considered as hallmarks. We found a significant correlation between K16(+) cell increment and the increase in epidermal thickness in the timeframe of 14 days. The change in CD3(+), CD4(+), and CD8(+) T-cell numbers in the dermis showed a significant association with these two features from d7 to d14, whereas in the epidermis only CD8(+) T cells demonstrated a significant correlation. Remarkably, the relationship between T cells and disease progression was preceded by a significant correlation of CD11c(+) dendritic cells (DCs) with K16 expression and epidermal thickness from baseline onwards. Interestingly, there was also a numeric correlation of CD11c(+) DCs with the CD3(+) T-cell shifts from d7 to d14. A significant correlation was also found between dermal CD14(+) cells and K16 expression from d7 to d14. BDCA-2(+) plasmacytoid DCs were absent in non-lesional skin, but found at low numbers in most lesions. The change in plasmacytoid DC or neutrophil numbers did not correlate with lesion development. In conclusion, our study suggests a relevant role for T cells, and in particular dermal CD11c(+) DCs, in the earliest stage of psoriatic lesion development.


Assuntos
Antígeno CD11c/análise , Células Dendríticas/imunologia , Psoríase/imunologia , Adulto , Idoso , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Psoríase/etiologia , Linfócitos T/imunologia
4.
Exp Dermatol ; 19(8): 754-6, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20482616

RESUMO

To investigate whether specific markers for innate immunity would diminish with successful treatment in psoriasis, we analyzed lesional and non-lesional skin biopsies taken from patients with moderate to severe psoriasis during 12 weeks of treatment with etanercept in correlation with the clinical response. In the clinical responders (PASI reduction >50%), all markers (CD3, CD68, CD161, elastase, BDCA-2, TNF-alpha) showed a decline during treatment, indicating a pivotal role for innate immunity in the pathogenesis of psoriasis.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Imunidade Inata , Imunoglobulina G/uso terapêutico , Psoríase/tratamento farmacológico , Psoríase/patologia , Receptores do Fator de Necrose Tumoral/uso terapêutico , Pele/patologia , Adulto , Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/metabolismo , Biomarcadores/metabolismo , Biópsia , Complexo CD3/metabolismo , Etanercepte , Feminino , Humanos , Lectinas Tipo C/metabolismo , Masculino , Glicoproteínas de Membrana/metabolismo , Pessoa de Meia-Idade , Subfamília B de Receptores Semelhantes a Lectina de Células NK/metabolismo , Elastase Pancreática/metabolismo , Psoríase/metabolismo , Receptores Imunológicos/metabolismo , Pele/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
5.
Arch Dermatol Res ; 302(2): 113-23, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19517126

RESUMO

In psoriasis, leukocytes that infiltrate skin lesions have been shown to be involved in the pathogenesis of this disease. Previous investigations reporting the presence of CXCR3(+) T lymphocytes in psoriatic lesional skin have suggested a role of this receptor in the recruitment of T cells into the lesion. The purpose of this study was to quantify the mRNA levels of CXCR3 and to perform a systematic analysis of the cell populations that express CXCR3 in human lesional and non-lesional psoriatic biopsies. We showed by real-time reverse transcriptase-polymerase chain reaction that the mRNA levels of CXCR3 and its ligands, CXCL9-11, were significantly elevated in psoriatic lesions, as compared to non-lesional samples. Serial cryostat sections of psoriasis skin biopsies were evaluated by immunohistochemistry. The number of CXCR3(+) cells was low in non-lesional tissues. Quantitative image analysis demonstrated significant increases in the number of both epidermal and dermal CXCR3(+) cells in lesional compared with non-lesional biopsies. The majority of CXCR3(+) cells were located in the dermis of the lesional skin and 74% were demonstrated to be CD3(+) T lymphocytes. A small number of CXCR3(+) cells were CD68(+) myeloid cells. In addition, we found that nearly all BDCA-2(+) plasmacytoid dendritic cells in the psoriatic biopsies were CXCR3(+). These findings support and extend prior reports suggesting the potential role for CXCR3 in the pathophysiology of plaque psoriasis, by mediating the recruitment of plasmacytoid dendritic cells and T cells into the developing lesions.


Assuntos
Células Dendríticas/imunologia , Linfócitos/imunologia , Psoríase/imunologia , Receptores CXCR3/fisiologia , Pele/imunologia , Contagem de Células , Imunofluorescência , Humanos , Imuno-Histoquímica , Psoríase/etiologia , Psoríase/patologia , Psoríase/terapia , RNA Mensageiro/análise , Receptores CXCR3/análise , Receptores CXCR3/antagonistas & inibidores , Receptores CXCR3/genética , Pele/patologia
6.
Arch Dermatol Res ; 299(7): 305-13, 2007 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-17647003

RESUMO

Several reports have indicated that the chemokine receptor CCR5 and its ligands, especially CCL5 (formerly known as RANTES), may play a role in the pathogenesis of psoriasis. The purpose of this investigation was to examine the expression of CCR5 and its ligands in chronic plaque psoriasis and to evaluate the clinical and immunohistochemical effect of a CCR5 receptor inhibitor. Immunohistochemical analysis showed low but significant increased total numbers of CCR5 positive cells in epidermis and dermis of lesional skin in comparison to non-lesional skin. However, relative expression of CCR5 proportional to the cells observed revealed that the difference between lesional and non-lesional skin was only statistically significant in the epidermis for CD3 positive cells and in the dermis for CD68 positive cells. Quantification of mRNA by reverse transcriptase-polymerase chain reaction only showed an increased expression of CCL5 (RANTES) in lesional skin. A randomized placebo-controlled clinical trial in 32 psoriasis patients revealed no significant clinical effect and no changes at the immunohistochemical level comparing patients treated with placebo or a CCR5 inhibitor SCH351125. We conclude that although CCR5 expression is increased in psoriatic lesions, this receptor does not play a crucial role in the pathogenesis of psoriasis.


Assuntos
Antagonistas dos Receptores CCR5 , Óxidos N-Cíclicos/uso terapêutico , Piperidinas/uso terapêutico , Psoríase/tratamento farmacológico , Piridinas/uso terapêutico , Adulto , Idoso , Método Duplo-Cego , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Oximas , Receptores CCR5/análise , Receptores CCR5/genética , Receptores CCR5/fisiologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Pele/química
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