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1.
Fitoterapia ; 139: 104394, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31669719

RESUMO

Naturally occurring monoterpenes are known for their various pharmacological activities including anti-inflammation. KV1.3 ion channel is a voltage-gated potassium channel and has been validated as a drug target for autoimmune and chronic inflammatory diseases like psoriasis. Here we experimentally test the direct interaction between monoterpenes and KV1.3 ion channel. Our electrophysiological analysis determined that monoterpenes (geraniol, nerol, ß-citronellol, citral and linalool) have inhibitory effects on KV1.3 ion channel. Representatively, geraniol reversibly blocked KV1.3 currents in a voltage-dependent manner with an IC50 of 490.50 ±â€¯1.04 µM at +40 mV in HEK293T cells. At the effective concentrations, geraniol also inhibited cytokine secretion of activated human T cells, including IL-2, TNF-α and IFN-γ. In an imiquimod-induced psoriasis-like animal model, geraniol administration significantly reduced psoriasis area and severity index scores, ameliorated the deteriorating histopathology and decreased the degree of splenomegaly. Together, our findings not only suggest that monoterpenes may serve as lead molecules for the development of KV1.3 inhibitors, but also indicate that geraniol could be considered as a promising therapeutic candidate to treat autoimmune diseases.


Assuntos
/farmacologia , Anti-Inflamatórios/farmacologia , Canal de Potássio Kv1.3/antagonistas & inibidores , Bloqueadores dos Canais de Potássio/farmacologia , Animais , Citocinas/metabolismo , Modelos Animais de Doenças , Células HEK293 , Humanos , Masculino , Camundongos Endogâmicos BALB C , Psoríase/tratamento farmacológico , Linfócitos T/efeitos dos fármacos , Linfócitos T/metabolismo
3.
J Environ Pathol Toxicol Oncol ; 38(3): 285-295, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31679314

RESUMO

Psoriasis is an autoregulated immune and inflammation-based skin disease affecting approximately 3-4% of the worldwide population. Pinitol, conservatively used in ayurvedic medicine, has been shown to disclose an antiinflammatory effect, hold back the T-helper cells, and postpone cardiovascular diseases. In the present study we aimed to reveal the effect of D-pinitol on imiquimod (IMQ)-induced psoriasis-like skin inflammation in a mouse model via the nuclear factor-κB (NF-κB) pathway genes. In the current study, we found that D-pinitol ameliorated the skin abrasion and abridged epithelial thickness, inflammation numbers, and collagen-occupied regions in IMQ-induced psoriasis-like mice. The same results (epithelial thickness, inflammation numbers, and collagen-occupied regions) we achieved in dorsal skin regions. In addition, D-pinitol modified the lipid profile and antioxidant enzyme levels, which means that the IMQ-induced group showed elevated malondialdehyde when compared to D-pinitol. Downregulated expression of glutathione, superoxide dismutase, and catalase in the IMQ-induced group was incomparable with D-pinitol, control, and standard group. Additionally, inflammatory and NF-kB pathway gene levels in the psoriatic mouse skin, which includes tumor necrosis factor-α, interleukin [IL]-6, IL-17A, IL-23,TRAF3, NIK, IKKα, and RelB, were dramatically increased or decreased by treatment with D-pinitol. Histological and morphometric studies disclose the efficiency of D-pinitol. Finally, we found that D-pinitol reserved the TRAF3, NIK, IKKα, and RelB in the psoriatic skin, signifying that it restrains the commencement of NF-κB signaling pathways. The present results suggest that D-pinitol could prove to have tremendous preventive potential against the treatment and prevention of inflammatory disease.


Assuntos
Anti-Inflamatórios/farmacologia , Imiquimode/imunologia , Inflamação/tratamento farmacológico , Inositol/análogos & derivados , Psoríase/tratamento farmacológico , Animais , Inflamação/induzido quimicamente , Inflamação/imunologia , Inositol/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , NF-kappa B/imunologia , Psoríase/imunologia
4.
Hautarzt ; 70(12): 934-941, 2019 Dec.
Artigo em Alemão | MEDLINE | ID: mdl-31740978

RESUMO

Modern dermatotherapy is dominated by the development of various biologicals and small molecules. Janus kinase inhibitors (JAKi) form a novel class of small molecular synthetic compounds inhibiting the intracellular signal transduction of cytokine receptors. Cytokines are key mediators in the pathophysiology of numerous inflammatory skin diseases. Many cytokines use so-called type I and II cytokine receptors, which associate with the Janus kinases JAK1, JAK2, JAK3 or TYK2. JAKi are under clinical investigation for inflammatory skin disease, specifically in phase 3 trials for psoriasis or atopic dermatitis. Since JAKi are tested in oral as well as in topical formulations, they could become very popular in dermatotherapy. The mechanisms of JAKi, their selectivity, preliminary efficacy data, and their safety profile are discussed in this article.


Assuntos
Dermatite Atópica , Inibidores de Janus Quinases , Psoríase , Citocinas , Dermatite Atópica/tratamento farmacológico , Humanos , Inibidores de Janus Quinases/farmacologia , Inibidores de Proteínas Quinases , Psoríase/tratamento farmacológico
5.
Hautarzt ; 70(12): 942-947, 2019 Dec.
Artigo em Alemão | MEDLINE | ID: mdl-31728551

RESUMO

Coal tar therapy was used for centuries to treat skin disorders characterised by inflammation and skin barrier damage. It has been shown that the aryl hydrocarbon receptor (AhR) is the key target structure for these pharmacological effects of coal tar. Since coal tar has been used less and less because of the carcinogenicity of many ingredients of coal tar, other ligands of AhR were studied. Tapinarof is such a ligand and proved to be a promising new drug to treat psoriasis and atopic dermatitis. Since many endogenous and exogenous ligands of AhR are known, it may be that this "tar-smart" product is a first example of a new drug family with which dermatologists can treat skin disorders that are characterized by inflammation and skin barrier damage.


Assuntos
Dermatite Atópica , Eczema , Psoríase , Receptores de Hidrocarboneto Arílico , Alcatrão/farmacologia , Dermatite Atópica/tratamento farmacológico , Eczema/tratamento farmacológico , Humanos , Psoríase/tratamento farmacológico , Receptores de Hidrocarboneto Arílico/efeitos dos fármacos
8.
Drugs Today (Barc) ; 55(9): 587-593, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31584575

RESUMO

Generalized pustular psoriasis (GPP) is a severe psoriasis form that can be refractory to several systemic treatments. The role of interleukin (IL)-17/ T-helper 17 (Th17) axis inhibitors in the therapy of GPP is not fully established. The objective of this paper is to summarize the existing information on the efficacy and safety of secukinumab, ixekizumab and brodalumab in GPP. Articles published in the English language and derived from the databases MEDLINE (PubMed), Embase and Scopus were assessed for this study. Although the existing data on the potential therapeutic benefit of these agents in the treatment of GPP are encouraging, further studies are needed so as to provide sufficient evidence for their use in this serious condition.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Interleucina-17 , Psoríase/tratamento farmacológico , Receptores de Interleucina-17/antagonistas & inibidores , Humanos , Imunossupressores
9.
J Drugs Dermatol ; 18(10): 1012-1018, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31584780

RESUMO

Background: The use of topical therapy is a key component in the management of almost all psoriasis patients. Topicals are considered first-line therapy for mild disease and are having an increasing role in moderate or severe psoriasis as an integral part of combination therapy. Halobetasol has been shown be effective in moderate or severe localized plaque psoriasis, and tazarotene affords important effects on epidermal hyperproliferation that may be important in more severe disease. Objective: To investigate the efficacy, safety and tolerability of a once-daily application of a fixed combination halobetasol propionate 0.01% and tazarotene 0.045% (HP/TAZ) lotion in comparison with its vehicle in patients with severe localized plaque psoriasis (as defined by an Investigator Global Assessment (IGA) of 4 and Body Surface Area (BSA) of 3%-12%. Methods: Post hoc analysis of two multicenter, randomized, double-blind, vehicle-controlled phase 3 studies. Sixty-two patients with severe localized psoriasis (mean BSA 7.4) randomized (2:1) to receive HP/TAZ lotion or vehicle, once-daily for 8 weeks, with a 4-week posttreatment follow-up. Efficacy assessments included treatment success (defined as at least a 2-grade improvement from baseline in the IGA score and a score of 'clear' or 'almost clear'), impact on individual signs of psoriasis (erythema, plaque elevation, and scaling) at the target lesion, BSA, reduction in mean baseline IGAxBSA and achievement of a clinically meaningful response (number of patients who achieved at least a 75% improvement in IGAxBSA). Safety and treatment emergent adverse events (TEAEs) were evaluated throughout. Results: By week 8, 34.8% of patients were treatment successes compared with 0.0% on vehicle (P=0.004). HP/TAZ lotion was also significantly superior in reducing psoriasis signs and symptoms and improving BSA. At week 8, 47.4% (erythema), 66.4% (plaque elevation), and 65.4% (scaling) subjects achieved at least a 2-grade improvement, compared with 14.0% (P=0.016), 14.8% (P<0.001) and 14.7% (P<0.001) respectively with vehicle. Patients treated with HP/TAZ lotion achieved a 32.8% reduction in baseline mean BSA, compared with a 39.6% increase with vehicle (P=0.013). HP/TAZ lotion achieved a statistically significant superior reduction in mean IGAxBSA compared to vehicle from week 2 (P<0.001 versus vehicle). By week 8, almost half of the patients treated with HP/TAZ lotion achieved a clinically meaningful response (IGAxBSA-75) and a 52.9% reduction in mean IGAxBSA score compared with a 17.5% increase in those patients treated with vehicle (P<0.001). One patient (2.6%) treated with HP/TAZ lotion discontinued due to AE. Most frequently reported treatment related AEs were application site pain (7.9%), contact dermatitis (5.3%) and pruritus (5.3%). Conclusions: HP/TAZ lotion provides significantly greater efficacy than vehicle that is both rapid and sustained, in patients with severe localized plaque psoriasis, with good tolerability and safety over 8 weeks' once-daily use. J Drugs Dermatol. 2019;18(10):1012-1018.


Assuntos
Clobetasol/análogos & derivados , Fármacos Dermatológicos/administração & dosagem , Ácidos Nicotínicos/administração & dosagem , Psoríase/tratamento farmacológico , Creme para a Pele/administração & dosagem , Adulto , Clobetasol/administração & dosagem , Clobetasol/efeitos adversos , Dermatite de Contato/epidemiologia , Dermatite de Contato/etiologia , Fármacos Dermatológicos/efeitos adversos , Método Duplo-Cego , Combinação de Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ácidos Nicotínicos/efeitos adversos , Dor/epidemiologia , Dor/etiologia , Prurido/epidemiologia , Prurido/etiologia , Psoríase/diagnóstico , Índice de Gravidade de Doença , Creme para a Pele/efeitos adversos , Resultado do Tratamento
10.
J Drugs Dermatol ; 18(10): 1029-1036, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31584782

RESUMO

Background: Psoriasis is a chronic, immune-mediated disease that varies widely in its clinical expression. Topical corticosteroids (TCS) are the mainstay of treatment. Long-term safety remains a concern, limiting use, and posttreatment flare is common. Recently data were reported on the use of halobetasol propionate (HP) 0.01% lotion in moderate or severe localized plaque psoriasis, once-daily for 8 weeks. In addition, a 2-week label-restricted study reported comparable efficacy to HP 0.05% cream. Data evaluating efficacy in specific locations has not been reported and while psoriasis commonly affects lower extremities treatment can be more problematic and burden of disease heightened. Objective: To investigate the efficacy of a once-daily application of HP 0.01% lotion in comparison with its vehicle in patients with moderate-to-severe plaque psoriasis of the lower extremities. Methods: A post hoc analysis of two multicenter, randomized, double-blind, vehicle-controlled phase 3 studies in moderate or severe psoriasis. Subjects (N=234) where the leg was identified as the target lesion were randomized (2:1 ratio) to receive HP 0.01% lotion or vehicle, once-daily for 8 weeks. Efficacy assessments included treatment success (defined as at least a 2-grade improvement from baseline) in each individual sign of psoriasis (erythema, plaque elevation, and scaling) at the target lesion (leg) and overall treatment outcomes including at least a 2-grade improvement from baseline in the Investigator Global Assessment (IGA) score, and 'clear' or 'almost clear', improvement in Body Surface Area (BSA) and reduction in IGAxBSA. Quality of Life (QoL) was assessed using the Dermatology Life Quality Index (DLQI) at baseline, week 4, 8, and 12. Results: At the end of the 8-week treatment period, more than half of subjects had achieved treatment success, with 52.1%, 55.5%, and 58.2% of subjects achieving at least a 2-grade reduction in erythema, plaque elevation and scaling severity on the leg, compared with 15.7% and 22.9%, and 22.2% of those treated with vehicle (P<0.001). In addition, overall treatment success (IGA) was achieved in 37.1% of these subjects who had been treated with HP 0.01% lotion compared with 8.4% treated with vehicle (P<0.001); with a corresponding 34.2% reduction in baseline BSA and 50.5% change in mean baseline IGAxBSA (both P<0.001 versus vehicle). Overall, a clinically relevant improvement in QoL was achieved by week 4; by week 8 37.7% of subjects where the leg was the target lesion had a clinically meaningful improvement in disease severity (IGAxBSA-75). Conclusions: In conclusion, halobetasol propionate 0.01% lotion provides statistically significant efficacy following 8 weeks' therapy compared with vehicle in subjects where the leg was identified as the target lesion, with clinically relevant improvements in QoL and more than a third of subjects achieving a clinically meaningful result. J Drugs Dermatol. 2019;18(10):1029-1036.


Assuntos
Clobetasol/análogos & derivados , Fármacos Dermatológicos/administração & dosagem , Psoríase/tratamento farmacológico , Creme para a Pele/administração & dosagem , Adulto , Idoso , Clobetasol/administração & dosagem , Clobetasol/efeitos adversos , Fármacos Dermatológicos/efeitos adversos , Método Duplo-Cego , Esquema de Medicação , Feminino , Humanos , Extremidade Inferior , Masculino , Pessoa de Meia-Idade , Psoríase/diagnóstico , Qualidade de Vida , Índice de Gravidade de Doença , Creme para a Pele/efeitos adversos , Resultado do Tratamento
11.
J Drugs Dermatol ; 18(10): 1059-1060, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31603636

RESUMO

To the Editor: Patients with psoriasis are at increased risk of developing non melanoma skin cancer (NMSC), including squamous cell carcinoma (SCC) and basal cell carcinoma (BCC).1,2 The risk is especially elevated among those who previously received systemic treatment or phototherapy.2 Systemic treatments, including biologic therapies and methotrexate (MTX), are effective in managing immune-mediated diseases; however, they may increase susceptibility to NMSC due to immunosuppression or other factors.3


Assuntos
Carcinoma Basocelular/epidemiologia , Carcinoma de Células Escamosas/epidemiologia , Fármacos Dermatológicos/efeitos adversos , Psoríase/tratamento farmacológico , Neoplasias Cutâneas/epidemiologia , Produtos Biológicos/efeitos adversos , Carcinoma Basocelular/induzido quimicamente , Carcinoma de Células Escamosas/induzido quimicamente , Humanos , Estudos Longitudinais , Metotrexato/efeitos adversos , Sistema de Registros/estatística & dados numéricos , Medição de Risco , Fatores de Risco , Neoplasias Cutâneas/induzido quimicamente
12.
Wien Klin Wochenschr ; 131(19-20): 485-492, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31591676

RESUMO

BACKGROUND: Fumaric acid esters are recommended in European guidelines for induction and maintenance treatment of patients with moderate to severe plaque psoriasis. A systemic medication with pure dimethyl fumarate without monoethyl fumarate salts was recently licensed in Europe. OBJECTIVE: The efficacy and safety of pure dimethyl fumarate were assessed in patients with severe (physician global assessment) plaque psoriasis in Austria in the BRIDGE trial. METHODS: In this double blind, randomized, placebo-controlled trial patients received 16-week treatment with pure dimethyl fumarate in a head to head comparison with dimethyl fumarate with monoethyl fumarate salts, which is licensed in Germany. In this post hoc analysis the efficacy and safety were assessed in patients with severe psoriasis in Austria. RESULTS: Efficacy measures significantly improved in both active treatment arms compared to placebo in 65 patients after 16 weeks of treatment. Physician global assessment of clear/almost clear in the dimethyl fumarate group was non-inferior to the dimethyl fumarate with monoethyl fumarate salts group 2 months after end of treatment. No serious adverse reaction occurred in patients with dimethyl fumarate in contrast to the second active treatment. Efficacy outcome was paralleled by quality of life improvements. CONCLUSION: This is the first report of dimethyl fumarate in a severely affected population with plaque psoriasis. Dimethyl fumarate is effective and safe in the systemic treatment of adults with severe psoriasis (physician global assessment).


Assuntos
Fumarato de Dimetilo , Psoríase , Adulto , Idoso , Áustria , Fumarato de Dimetilo/efeitos adversos , Fumarato de Dimetilo/uso terapêutico , Método Duplo-Cego , Europa (Continente) , Feminino , Alemanha , Humanos , Masculino , Pessoa de Meia-Idade , Psoríase/tratamento farmacológico , Qualidade de Vida , Índice de Gravidade de Doença , Resultado do Tratamento , Adulto Jovem
13.
Expert Opin Drug Metab Toxicol ; 15(11): 913-925, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31623470

RESUMO

Introduction: The treatment of psoriasis with conventional topical therapies and disease-modifying anti-rheumatic drugs (DMARDs) is often linked to unsatisfactory outcomes and the risk of serious adverse events. Over the last decades, research advances in understanding the role of tumor necrosis factor alpha (TNF α) and other cytokines in the pathogenesis of psoriasis have driven the introduction of biologic agents targeting specific immune mediators in everyday clinical practice. TNF α inhibitors are a consolidated treatment option for patients with moderate-to-severe disease with remarkable efficacy and a reassuring safety profile.Areas covered: The PubMed database was searched using combinations of the following keywords: psoriasis, TNF α inhibitors, biologic therapy, pharmacodynamics, adalimumab, etanercept, infliximab, certolizumab pegol, golimumab, adverse effects. The aim of this review is to describe the pharmacodynamic profile of anti-TNF α inhibitors, currently approved by the European Medicines Agency (EMA) for the treatment of psoriasis, focusing on related clinical implications, also in comparison to the new generation biological therapies targeting the interleukin 23/interleukin 17 axis.Expert opinion: Pharmacodynamics of TNF α inhibitors should be fully considered in planning patient's therapy strategies, especially in case of secondary failures, poor adherence to treatment, instable psoriasis, high risk of infection, pregnant or lactating women, metabolic comorbidities, coexistence of other immune-mediated inflammatory diseases.


Assuntos
Fármacos Dermatológicos/administração & dosagem , Psoríase/tratamento farmacológico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Animais , Antirreumáticos/administração & dosagem , Antirreumáticos/efeitos adversos , Antirreumáticos/farmacologia , Fármacos Dermatológicos/efeitos adversos , Fármacos Dermatológicos/farmacologia , Desenvolvimento de Medicamentos , Humanos , Fatores Imunológicos/administração & dosagem , Fatores Imunológicos/efeitos adversos , Fatores Imunológicos/farmacologia , Adesão à Medicação , Psoríase/imunologia , Psoríase/patologia , Índice de Gravidade de Doença , Fator de Necrose Tumoral alfa/metabolismo
14.
Arq Gastroenterol ; 56(3): 261-263, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31633722

RESUMO

BACKGROUND: Psoriasis is an inflammatory skin disease that affects 1%-3% of Caucasian populations and may be persistent, disfiguring and stigmatising. Proton pump inhibitors (PPI) are potent blockers of gastric acid secretion. They are widely regarded as the agents of choice for the treatment of acid-peptic disorders. In addition to anti-secretory effects PPI have been found to have anti-oxidant properties and direct effects on neutrophils, monocytes, endothelial, and epithelial cells that might prevent inflammation. OBJECTIVE: This study evaluated the treatment of psoriasis with esomeprazole. METHODS: Ten patients were selected and psoriasis was evaluated according to Psoriasis Area and Severity Index (PASI). Exclusion criteria included concomitant use of any treatment for Psoriasis, organic diseases, use of other PPI than esomeprazole. Patients were medicated with esomeprazole 40 mg B.I.D. for 90 days. At the 90th day the patients were evaluated according PASI score. RESULTS: Statistically significant results were seen when compared PASI before and at 90th day of treatment (P=0.0002). CONCLUSION: The use of esomeprazole for psoriasis resulted in excellent clinical results with a significant reduction of PASI score.


Assuntos
Esomeprazol/uso terapêutico , Inibidores da Bomba de Prótons/uso terapêutico , Psoríase/tratamento farmacológico , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto
15.
Brasília; CONITEC; out. 2019. tab.
Não convencional em Português | BRISA/RedTESA | ID: biblio-1024748

RESUMO

INTRODUÇÃO: Psoríase é uma doença crônica não contagiosa, que acomete principalmente a pele e as articulações, e com grande impacto na qualidade de vida dos pacientes. A forma clínica da psoríase em placas (ou vulgar) é a mais frequente e apresenta-se com manchas vermelhas e descamação, podendo apresentar coceira e dor nos casos mais graves. A prevalência no Brasil é entre 0,92% e 1,88% e os casos moderados a grave correspondem de 20% a 30% dos pacientes. No SUS, o tratamento dos pacientes moderados a graves inclui fototerapia e tratamentos sistêmicos não biológicos com metotrexato, acitretina e ciclosporina. Em 2018 foi incluído adalimumabe na primeira etapa de tratamento biológico, após falha à terapia sistêmica não biológica, e secuquinumabe e ustequinumabe como opções após o adalimumabe. TECNOLOGIA: Secuquinumabe (Cosentyx®). PERGUNTA: Em pacientes adultos com psoríase em placas, moderada a grave, que apresentaram resposta inadequada, perda de resposta ou intolerância à terapia sistêmica não biológica (metotrexato, acitretina e ciclosporina), o uso de secuquinumabe (Cosentyx®) proporciona melhor controle dos sintomas (PASI≥90), melhor qualidade de vida (DLQI 0/1), menor frequência de óbitos, eventos adversos graves e infecções graves, quando comparado ao adalimumabe e ao ustequinumabe no longo prazo (1 ano ou mais)? EVIDÊNCIAS CIENTÍFICAS: Secuquinumabe demonstrou superioridade em relação ao ustequinumabe em um ECR, com maior frequência de controle dos sintomas entre 4 e 52 semanas de acompanhamento em pacientes virgens de biológicos e em melhora da qualidade de vida (evidência com qualidade alta). Não foram identificados estudos de intervenção de comparação direta entre secuquinumabe e adalimumabe, concluídos ou em andamento. Metaanálise em rede Bayesiana não identificou diferença estatística entre secuquinumabe e adalimumabe em relação ao controle total dos sintomas em 52 semanas de acompanhamento, com intervalo de credibilidade extenso (evidência com qualidade baixa). Não foram identificadas diferenças entre secuquinumabe e ustequinumabe ou adalimumabe em desfechos de segurança. AVALIAÇÃO ECONÔMICA: Por meio de modelo de árvore de decisão, sob a perspectiva do SUS, e considerando o preço inicialmente proposto do secuquinumabe de R$ 634,00, o demandante estimou que o secuquinumabe apresenta o menor custo por resposta PASI≥90 (pele sem lesões ou quase sem lesões) em 16 semanas (R$ 13.295,53 por PASI≥90) e em 52 semanas (R$ 30.796,36 por PASI≥90) de acompanhamento, quando comparado ao adalimumabe e ao ustequinumabe. Os resultados não foram alterados após análise de sensibilidade. Incertezas em parâmetros importantes do modelo diminuem a confiança nas estimativas apresentadas. AVALIAÇÃO DE IMPACTO ORÇAMENTÁRIO: O impacto orçamentário estimado pelo demandante para a alteração de linha do secuquinumabe é de R$ 3,9 milhões no primeiro ano e um acumulado de R$ 15,9 milhões em 5 anos. Com a nova proposta de preço do secuquinumabe, de R$ 628,00 por 150mg/ml, o custo por paciente do tratamento com secuquinumabe no primeiro ano é de R$ 21.352,00. Adalimumabe apresenta custo no primeiro ano de R$ 13.365,52 e o ustequinumabe de R$ 24.673,65. MONITORAMENTO DO HORIZONTE TECNOLÓGICO: Foram identificadas 12 tecnologias em fase avançada de desenvolvimento clínico para o tratamento de pacientes com psoríase moderada a grave, incluindo medicamentos de uso oral e com registro na Anvisa. CONFLITOS DE INTERESSES: os elaboradores deste relatório declaram não possuir conflitos de interesses com a matéria em análise. RECOMENDAÇÃO PRELIMINAR: Considerou-se que secuquinumabe demonstra superioridade em eficácia e em custo de tratamento em comparação ao ustequinumabe. Em comparação ao adalimumabe, por outro lado, não se demonstrou superioridade e, portanto, não se justifica um custo de tratamento superior do secuquinumabe para que possam estar ambos posicionados na mesma etapa de tratamento. Assim, a CONITEC em 03/07/2019, recomendou a não incorporação no SUS do secuquinumabe (Cosentyx®) para o tratamento de pacientes adultos com psoríase em placas, moderada a grave, na primeira etapa de tratamento biológico, após falha da terapia sistêmica não biológica, na mesma etapa em que se encontra o adalimumabe. CONSULTA PÚBLICA: Foram recebidas 16 contribuições técnico-científicas e 590 contribuições de experiência ou opinião, todas contrárias à recomendação preliminar da CONITEC. Considerouse que as argumentações ressaltaram a importância do medicamento na linha de tratamento da psoríase, mas não justificaram a alteração do seu posicionamento para a primeira etapa da terapia biológica. A CONITEC entendeu que não houve argumentação suficiente para alterar sua recomendação inicial. RECOMENDAÇÃO FINAL: Os membros da CONITEC em 04/09/2019 deliberaram por recomendar a não incorporação do secuquinumabe como primeira etapa de terapia biológica para o tratamento da psoríase em placas moderada a grave em pacientes adultos. Foi assinado o Registro de Deliberação nº 466/2019.


Assuntos
Humanos , Psoríase/tratamento farmacológico , Anticorpos Monoclonais/uso terapêutico , Avaliação da Tecnologia Biomédica , Sistema Único de Saúde , Brasil , Análise Custo-Benefício/economia
16.
Expert Rev Clin Pharmacol ; 12(10): 981-989, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31498683

RESUMO

Introduction: Psoriasis is affected by many environmental factors, including infections and antibiotics. However, the relationship between antibiotics and psoriasis is inadequately studied. Some antibiotics were listed as triggering factors; others showed benefit for psoriasis control. The aim of this article is to review current evidence that may help identify appropriate antibiotics for patients with psoriasis. Areas covered: The PubMed, Embase, Clinicalkey databases, and google scholar were searched for relevant articles published up to May 2019. Literature regarding antibiotics and psoriasis were included. Six randomized controlled trials and four controlled or cohort studies were identified in 13 kinds of antibiotics. Expert opinion: Macrolides and rifampin showed decrease of psoriasis area and severity index score in plaque-type psoriasis, while penicillin revealed no statistically significant improvement in guttate psoriasis. Previously tetracyclines were considered as triggering factors, but data were found only in cases or retrospective studies. Mechanisms were thought to be related to immunomodulation rather than bacteria inhibition. Research gap in the influence of genetic susceptibility, the impact on microbiota, and the mode of actions remain to be investigated.


Assuntos
Antibacterianos/uso terapêutico , Fatores Imunológicos/uso terapêutico , Psoríase/tratamento farmacológico , Animais , Antibacterianos/efeitos adversos , Antibacterianos/farmacologia , Humanos , Fatores Imunológicos/farmacologia , Macrolídeos/efeitos adversos , Macrolídeos/farmacologia , Macrolídeos/uso terapêutico , Psoríase/patologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Rifampina/efeitos adversos , Rifampina/farmacologia , Rifampina/uso terapêutico , Índice de Gravidade de Doença
17.
Expert Opin Drug Saf ; 18(11): 1031-1041, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31479282

RESUMO

Introduction: Psoriasis is a chronic inflammatory disease and affects about 10% of the world's population. Psoriasis is associated with a number of comorbidities. Biologic therapies for the treatment of moderate-severe plaque psoriasis include tumor necrosis factor α inhibitors (TNFi), and newer molecules targeting IL-12 and 23, blocking p40 subunit, or targeting subunit p19 of IL-23 and other molecules blocking IL-17A, or directed against the IL-17 receptor. Areas covered: Anti-interleukin drugs show great improvement in disease control and on the other hand are not affected by important adverse reactions of older compounds. Approach to chronic disease affected patients, in particular, and to patients with multiple comorbidities is revolutionized by novel molecules that are safer and more manageable. Expert opinion: A recent work suggests that pro-fibrogenic cytokines, IL-17, might be important player of liver damage and even in regulation of obesity, diabetes, and non-alcoholic fatty liver disease (NAFLD) pathogenesis. Choosing to interfere with IL-23/Il-17 axis, definitely, is like acting against psoriatic march and in a parallel way against its comorbidities.


Assuntos
Anticorpos Monoclonais/administração & dosagem , Fármacos Dermatológicos/administração & dosagem , Psoríase/tratamento farmacológico , Animais , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/imunologia , Produtos Biológicos/administração & dosagem , Produtos Biológicos/efeitos adversos , Produtos Biológicos/imunologia , Fármacos Dermatológicos/efeitos adversos , Fármacos Dermatológicos/imunologia , Humanos , Interleucina-12/imunologia , Interleucina-17/imunologia , Interleucina-23/imunologia , Psoríase/imunologia , Psoríase/patologia , Índice de Gravidade de Doença
18.
Biol Res ; 52(1): 49, 2019 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-31492195

RESUMO

BACKGROUND: Psoriasis is a common and intractable skin disease affecting the physical and mental health of patients. The accumulation of ROS is involved in the pathogenesis of psoriasis and antioxidants are believed to be therapeutic. This study aimed to investigate the therapeutic efficacy of astilbin on ROS accumulation in psoriasis. RESULTS: The study showed that 50 µg/ml astilbin could inhibit the growth and reduce the accumulation of ROS in HaCaT cells stimulated by IL-17 and TNF-α. Astilbin could elevate the Nrf2 accumulation in the nuclei, eventually leading to the transcriptional activation of various antioxidant proteins and reducing the expression of VEGF. CONCLUSIONS: Our results collectively suggest that astilbin could induce Nrf2 nucleus translocation, which is contribute to reduce the ROS accumulation and VEGF expression, and inhibit the proliferation of HaCaT cells.


Assuntos
Flavonóis/administração & dosagem , Queratinócitos/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/efeitos dos fármacos , Psoríase/tratamento farmacológico , Espécies Reativas de Oxigênio/metabolismo , Fator A de Crescimento do Endotélio Vascular/efeitos dos fármacos , Animais , Modelos Animais de Doenças , Interleucina-17/metabolismo , Queratinócitos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Fator 2 Relacionado a NF-E2/metabolismo , Psoríase/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fator de Necrose Tumoral alfa/efeitos dos fármacos , Fator de Necrose Tumoral alfa/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo
19.
Dokl Biochem Biophys ; 487(1): 272-276, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31559596

RESUMO

Psoriasis therapy remains an extremely relevant area of modern drug design, due to necessity of adverse reaction reduction, inherent for actual methods of therapy. It was established that two serine proteases-neutrophil elastase 1 (HNE1) and cathepsin G (CatG)-are the key agents in psoriasis development. The collected molecular data for the presented targets form the basis for the molecular modeling strategy for the search for and identification of new target-specific inhibitors. The result of this work is a group of high-priority small-molecule compounds with double-targeted affinity, which are able to suppress the pro-psoriatic processes induced by the considered serine proteases at the initial stage of the disease.


Assuntos
Catepsina G/antagonistas & inibidores , Elastase de Leucócito/antagonistas & inibidores , Terapia de Alvo Molecular , Psoríase/tratamento farmacológico , Inibidores de Serino Proteinase/farmacologia , Catepsina G/química , Descoberta de Drogas , Elastase de Leucócito/química , Modelos Moleculares , Conformação Proteica , Psoríase/enzimologia , Inibidores de Serino Proteinase/uso terapêutico
20.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 35(7): 595-600, 2019 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-31537243

RESUMO

Objective To observe the effect of esculentoside A (EsA) on Th17 cell-related factors in psoriasis-like mouse model. Methods A total of 48 female BALB/c mice were randomly divided into blank control group, model group, Tuiyin decoction group [66.60 g/(kg.d)], low-, middle- and high-dose groups of EsA [5, 10, 20 mg/(kg.d), respectively], 8 mice in each group. Psoriasis mouse model was induced by imiquimod. Pathological changes of skin lesions in mice were assessed by psoriasis area and severity index (PASI) and HE staining. ELISA was used to detect the changes of interleukin-17 (IL-17), IL-22, IL-6 and tumor necrosis factor-α (TNF-α). Results Compared with the model group, the skin lesions, pathological changes and PASI scores were improved after the treatments with either Tuiyin decoction or EsA, among which the PASI score of Tuiyin decoction group and high-dose group of EsA decreased significantly. The expression of Th17 cell-related factors of the model group was obviously higher than that of the blank control group. Each treated group had obviously lower expression than the model group, and the expression of IL-6 of high-dose group of EsA was close to the blank control group. Conclusion EsA may improve the skin lesions of the psoriasis-like mice by down-regulating the expression of Th17 cell-related cytokines.


Assuntos
Dermatite/tratamento farmacológico , Ácido Oleanólico/análogos & derivados , Psoríase/tratamento farmacológico , Saponinas/farmacologia , Células Th17/imunologia , Animais , Citocinas/imunologia , Dermatite/imunologia , Feminino , Imiquimode , Camundongos , Camundongos Endogâmicos BALB C , Ácido Oleanólico/farmacologia , Psoríase/induzido quimicamente , Distribuição Aleatória , Pele/imunologia , Pele/patologia
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