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1.
Braz J Med Biol Res ; 52(12): e8565, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31778437

RESUMO

This study aimed to investigate the correlation of ultrasonography (US) of synovitis with disease activity and clinical response to etanercept (ETN) in juvenile idiopathic arthritis (JIA) patients. Eighty-two JIA patients who underwent ETN treatment for 24 weeks were consecutively enrolled. US evaluations of 28 joints (shoulder, elbow, wrist, metacarpophalangeal, and proximal interphalangeal of hands and knee) at baseline were performed using grey-scale US and power doppler (PD) US, and US synovitis was defined as grey-scale abnormalities or PD abnormalities. Clinical response was assessed according to the ACRpedi 50 response criteria. In total, 2296 joints were scanned and 608 (26.5%) joints presented US synovitis, which was numerically higher than clinical synovitis (513 (22.3%)). The mean number of joints showing synovitis on US was 7.42±3.35, which was also numerically higher than that of clinical synovitis (6.26±2.70). The number of joints showing synovitis on US was positively correlated with C-reactive protein, erythrocyte sedimentation rate, number of joints with active disease, number of joints with limited range of motion, physician's global assessment of disease activity, parent/patient global assessment of overall well-being, and childhood health assessment questionnaire score. Most interestingly, the baseline number of joints showing synovitis on US was increased in ACRpedi 50 response JIA patients compared to non-response JIA patients, and it serves as an independent predictive factor for higher clinical response to ETN treatment. In conclusion, US is a more sensitive test to evaluate subclinical synovitis and disease activity in JIA patients, and US synovitis might serve as a marker for predicting increased clinical response rate to ETN treatment.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Artrite Juvenil/tratamento farmacológico , Etanercepte/uso terapêutico , Sinovite/diagnóstico por imagem , Artrite Juvenil/complicações , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Sinovite/complicações , Ultrassonografia
4.
Drugs Aging ; 36(9): 853-862, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31292906

RESUMO

BACKGROUND: Elderly individuals are disproportionately affected by rheumatoid arthritis (RA), but few studies have addressed the efficacy and safety of treatments in this population. OBJECTIVE: Our objective was to assess the efficacy and safety of etanercept in elderly patients (aged ≥ 65 years) with RA. METHODS: The efficacy analysis was a post hoc analysis of data from the open-label period of three phase IV clinical trials of etanercept for RA. Least squares (LS) change from baseline (cfb) in 28-joint Disease Activity Score (DAS28), Health Assessment Questionnaire Disability Index (HAQ-DI), and modified Total Sharp Scores (mTSS) were analyzed by age (< 65 vs. ≥ 65 years) for each study. The safety analyses were of data pooled from the double-blind, placebo-controlled periods of 19 phase I-IV randomized studies of etanercept in patients with RA. The percentage occurrence of adverse events (AEs) in placebo- and etanercept-treated patients was analyzed by age (< 65 vs. ≥ 65 years). RESULTS: There were no significant differences in LS mean cfb in DAS28 or mTSS between the two age groups. LS mean cfb in HAQ-DI scores was consistently lower in elderly than in non-elderly patients, although significant differences were not observed in all trials. Overall, AE occurrence was higher in elderly than non-elderly patients, regardless of treatment. In etanercept-treated patients, there were small yet statistically significant increases in the occurrence of congestive heart failure, serious infections, and non-melanoma skin cancers in elderly versus non-elderly patients. For most AEs, occurrence did not significantly differ between elderly and non-elderly patients. CONCLUSION: Overall, there were no substantial differences in the efficacy or safety of etanercept between elderly and non-elderly patients with RA.


Assuntos
Antirreumáticos/efeitos adversos , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Etanercepte/efeitos adversos , Etanercepte/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Segurança , Idoso , Método Duplo-Cego , Feminino , Humanos , Masculino , Resultado do Tratamento
6.
Expert Opin Pharmacother ; 20(14): 1777-1785, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31271541

RESUMO

Introduction: Psoriasis is a relatively common condition, with a lot of discordance in studies about the peak of onset. In a large German study, an almost linear prevalence increase was reported during childhood, ranging from 0.12% at 1 year to 1-2% at 18 years. According to recent studies, plaque psoriasis is the most common variant in childhood disease. Areas covered: This article focuses on topical, systemic and biologic therapies used in childhood psoriasis. The authors performed a full literature PubMed research, while incorporating case reports and experience. Topical agents are considered the first step, but they always have little efficacy in the extensive form of the disease. In this case, systemic and particularly biological therapy must be evaluated. The most studied treatment in the pediatric population is etanercept, but adalimumab and ustekinumab are also approved in pediatric and adolescent populations. Expert opinion: Larger studies are needed to further investigate the use of new compounds in childhood psoriasis. Recent evidence suggests that practitioners should consider interceding in the early immunologic psoriatic process to halt this march and stunt immunological scar development. An early investment would provide lasting effects and serious impact in long-term disease modification.


Assuntos
Imunossupressores/uso terapêutico , Psoríase/tratamento farmacológico , Adolescente , Anticorpos Monoclonais/uso terapêutico , Criança , Etanercepte/uso terapêutico , Humanos , Fototerapia , Esteroides/uso terapêutico , Vitamina D/análogos & derivados , Vitamina D/uso terapêutico
7.
Intern Med ; 58(17): 2551-2554, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31178497

RESUMO

Renal disease is a common complication of rheumatoid arthritis (RA) and can occur secondary to RA or be induced by therapeutic agents. Recently, glomerular deposition of galactose-deficient IgA1 (Gd-IgA1) was identified as a feature of primary IgA vasculitis with nephritis (IgA-VN). We herein report a case of IgA-VN in an RA patient whose disease activity was controlled by treatment with etanercept. To distinguish between primary IgA-VN and secondary IgA-VN caused by RA or etanercept, we performed immunostaining of renal biopsy sections with the Gd-IgA1-specific antibody KM55. Positive KM55 staining confirmed the diagnosis of primary IgA-VN in a patient with RA.


Assuntos
Artrite Reumatoide/complicações , Glomerulonefrite por IGA/diagnóstico , Imunoglobulina A/análise , Púrpura de Schoenlein-Henoch/diagnóstico , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Etanercepte/uso terapêutico , Feminino , Galactose/imunologia , Glomerulonefrite por IGA/etiologia , Glomerulonefrite por IGA/imunologia , Humanos , Pessoa de Meia-Idade , Púrpura de Schoenlein-Henoch/etiologia , Púrpura de Schoenlein-Henoch/imunologia
8.
Int Immunopharmacol ; 73: 442-450, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31154289

RESUMO

Etanercept has greatly improved management considerably. However, the efficacy and safety of combination therapy with methotrexate and the mechanism of action are not known. We aimed to describe the use of combined therapy of etanercept and methotrexate against moderate-to-severe plaque psoriasis in a Chinese population. We also wished to study the changes in expression of pro-inflammatory factors in peripheral blood mononuclear cells (PBMCs) and serum after the treatment to ascertain the mechanism of action. Thirty patients with moderate-to-severe plaque psoriasis were assigned into a monotherapy group and combination group randomly and equally. All patients received etanercept (50 mg, s.c., weekly), whereas patients in the combination group also received oral methotrexate (7.5-15 mg, p.o., weekly). Serum levels of interleukin (IL)-17A, IL-23, tumor necrosis factor (TNF)-α and their mRNA expressions in PBMCs were measured by ELISA and qRT-PCR. In the monotherapy group, Psoriasis Area and Severity Index (PASI) 50/75/90 responses were achieved by 86.7/66.7/40% after 24 weeks of treatment whereas, in the combination group, they were achieved by 93.3/80/60%, respectively. Although the overall prevalence of adverse effects (AEs) was higher in the combination group (60%) than in the monotherapy group (33.3%), the AEs were mild to moderate. The serum levels of IL-17A, IL-23, TNF-α, IL-33 and their mRNA expression in the PBMCs of the two groups were significantly higher than those of healthy controls (P < 0.05). Compared with the monotherapy group, serum levels of IL-17A, IL-23, TNF-α and their mRNA expression in PBMCs were decreased significantly in the combination group (P < 0.05). These data suggest that the efficacy of etanercept could be improved upon combination with methotrexate in the treatment of moderate-to-severe plaque psoriasis without increasing the risk of serious AEs. The mechanism of action might be associated with down-regulation of IL-17A, IL-23, and TNF-α.


Assuntos
Etanercepte/uso terapêutico , Imunossupressores/uso terapêutico , Metotrexato/uso terapêutico , Psoríase/tratamento farmacológico , Adulto , Idoso , Citocinas/imunologia , Quimioterapia Combinada , Feminino , Humanos , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/imunologia , Masculino , Pessoa de Meia-Idade , Psoríase/imunologia , Índice de Gravidade de Doença , Resultado do Tratamento
9.
Pediatrics ; 144(1)2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31243159

RESUMO

Coffin-Siris syndrome (CSS) and Nicolaides-Baraitser syndrome (NBS) are 2 overlapping syndromes caused by mutations in genes of the barrier-to-autointegration factor chromatin-remodeling complex, presenting with multiple malformations and intellectual disability. Musculoskeletal changes such as noninflammatory prominence of interphalangeal joints in hands, feet, and, to a lesser extent, knee joints are common in NBS (up to 85%) and also reported in CSS. We present the case of a 7-year-old boy with polyarthritis of several years' duration (without uveitis), developmental delay, microcephaly, and dysmorphic features reminiscent of NBS. Sanger sequencing of the SMARCA2 gene revealed no mutations. Laboratory test results were normal. With synovial biopsy, we confirmed a chronic inflammatory synovitis. Brain MRI revealed dysgenesis of the corpus callosum. Treatment with methotrexate and, subsequently, etanercept led to significant clinical improvement. Whole-exome sequencing revealed a de novo heterozygous nonsense mutation in the ARID1B gene, resulting in a premature stop codon (c.C5404T; p.R1802×), a genotype consistent with CSS. The absence of significantly raised inflammatory markers and a clinical diagnosis of a genetic syndrome associated with noninflammatory joint changes may have contributed to this patient's polyarthritis being missed for several years. We propose that some patients with CSS may have inflammatory arthritis (with or without coexisting skeletal dysplasia), which may be helped by treatment as described herein. Early recognition and treatment of inflammatory arthritis in CSS would have a significant impact on reducing disease burden and improving quality of life for patients with this rare genetic syndrome.


Assuntos
Anormalidades Múltiplas/diagnóstico , Artrite/diagnóstico , Face/anormalidades , Deformidades Congênitas da Mão/diagnóstico , Deficiência Intelectual/diagnóstico , Micrognatismo/diagnóstico , Pescoço/anormalidades , Anormalidades Múltiplas/genética , Anti-Inflamatórios não Esteroides/uso terapêutico , Artrite/tratamento farmacológico , Criança , Códon sem Sentido , Proteínas de Ligação a DNA/genética , Diagnóstico Diferencial , Etanercepte/uso terapêutico , Facies , Deformidades Congênitas do Pé/diagnóstico , Deformidades Congênitas da Mão/genética , Humanos , Hipotricose/diagnóstico , Deficiência Intelectual/genética , Masculino , Metotrexato/uso terapêutico , Micrognatismo/genética , Fatores de Transcrição/genética
10.
Ann Dermatol Venereol ; 146(5): 363-371, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31047699

RESUMO

BACKGROUND: The purpose of this study was to explore the correlation of anxiety and depression with therapeutic response to etanercept in psoriasis patients. PATIENTS AND METHODS: One hundred and thirty-three patients with moderate-to-severe plaque psoriasis undergoing etanercept treatment were consecutively enrolled in this prospective cohort study, with all patients receiving etanercept treatment for 6 months. Psoriasis Area and Severity Index (PASI) score was evaluated at baseline (M0) and at month 1 (M1), M3 and M6 after treatment, and PASI 75/90 responses were calculated. The Hospital Anxiety and Depression Scale-Anxiety (HADS-A) score and the HADS-Depression (HADS-D) score were used to evaluate patients' anxiety and depression at M0, M1, M3 and M6. Sustained anxiety/depression were defined as HADS-A/D score≥8points both at M0 and M1. RESULTS: Female gender and higher PASI score were associated with high risk of anxiety, while female gender, higher PASI score and longer disease duration were correlated with increased depression risk. After 6 months of etanercept treatment, 65.4% and 36.1% patients achieved PASI 75 and PASI 90 responses respectively, and both HADS-A and HADS-D scores were decreased. Most importantly, no correlation of baseline anxiety and depression with PASI 75 or PASI 90 response after 6 months of treatment was noted, while sustained depression, though not sustained anxiety, was observed to be correlated with decreased PASI 75 and PASI 90 responses. CONCLUSIONS: Etanercept reduces anxiety and depression in psoriasis patients, and sustained depression correlates with reduced therapeutic response to etanercept.


Assuntos
Ansiedade/diagnóstico , Depressão/diagnóstico , Etanercepte/uso terapêutico , Psoríase/tratamento farmacológico , Psoríase/psicologia , Ansiedade/etiologia , Depressão/etiologia , Etanercepte/administração & dosagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores Sexuais , Fatores de Tempo , Resultado do Tratamento
11.
BioDrugs ; 33(3): 241-253, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31111422

RESUMO

Adalimumab, the first fully humanised monoclonal antibody against tumour necrosis factor alpha (TNF-α), has played a leading role in the revolution brought about by the introduction of biologics, and has received the widest range of indications among TNF-α inhibitors. Post-registration, observational and registry studies of real-life use have largely supported the outcomes seen in registrational clinical trials. With the recent loss of exclusivity for the originator medicinal product in Europe, a number of biosimilar adalimumab molecules have been licensed for use in the same indications as the originator molecule across rheumatology, dermatology, gastroenterology and ophthalmology. Clinicians in these areas first gained experience with biosimilar infliximab, followed by etanercept and rituximab. However, adalimumab is likely to present unique challenges given the numbers of patients treated and the range of biosimilar adalimumab products available. The biosimilar approval pathway has an emphasis on the pre-clinical analytic data in combination with clinical studies conducted to confirm therapeutic equivalence. To date, several adalimumab biosimilars have entered the EU market following successful marketing authorisation applications and recent expiration of originator patent protection. This overview covers the extent of use of adalimumab and summarises the regulatory process involved in the development of biosimilars as well as their use in clinical practice. The authors also discuss clinical data available so far on adalimumab biosimilars and their envisaged impact in the field of immune-mediated inflammatory diseases.


Assuntos
Adalimumab/uso terapêutico , Medicamentos Biossimilares/uso terapêutico , Etanercepte/uso terapêutico , Europa (Continente) , Humanos , Infliximab/uso terapêutico , Rituximab/uso terapêutico , Equivalência Terapêutica
12.
Int J Rheum Dis ; 22(6): 967-973, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31025820

RESUMO

AIM: To investigate the point prevalence of depression and anxiety in psoriatic arthritis and putative reductions in these comorbidities with the treatment of psoriatic arthritis. METHOD: We performed a systematic review in accordance with PRISMA guidelines examining point prevalence of depression and anxiety in psoriatic arthritis as well as effects of treatment for psoriatic arthritis on these psychiatric comorbidities. MEDLINE, EMBASE, EBM Reviews and Cochrane, and PsycINFO were searched from inception to October 2017. Quality of studies was assessed using the Joanna Briggs Institute Checklist for Prevalence Studies. Study and population characteristics were extracted and entered into an electronic database for subsequent descriptive and meta-analysis of point prevalence. RESULT: Three studies matched inclusion criteria with significant statistical heterogeneity. The prevalence of depression ranged between 9%-22% and anxiety between 15%-30% in patients with psoriatic arthritis. One study matched inclusion criteria for treatment effect analysis, albeit with a high risk of bias and illustrated a benefit of etanercept on the prevalence of depression (9% vs 16%) and anxiety (14% vs 30%) after 24 weeks of treatment. CONCLUSION: This is the first systematic review of point prevalence of depression and anxiety in patients with psoriatic arthritis. There is a moderate point prevalence of both depression and anxiety in patients with psoriatic arthritis, which is similar or slightly higher than the general population and comparable to that seen in other rheumatic diseases. The effects of treatment for psoriatic arthritis on comorbid depression and anxiety remain unclear.


Assuntos
Afeto , Ansiedade/epidemiologia , Artrite Psoriásica/epidemiologia , Depressão/epidemiologia , Adulto , Idoso , Ansiedade/diagnóstico , Ansiedade/psicologia , Artrite Psoriásica/diagnóstico , Artrite Psoriásica/tratamento farmacológico , Artrite Psoriásica/psicologia , Comorbidade , Depressão/diagnóstico , Depressão/psicologia , Etanercepte/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Resultado do Tratamento , /uso terapêutico
14.
Biomed Pharmacother ; 112: 108740, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30970527

RESUMO

AIM: Anemia of chronic disease is considered the most common extra-articular manifestation of rheumatoid arthritis (RA). The present study aimed to investigate the effect of etanercept (anti-tumor necrosis factor) on anemia and hepcidin gene expression in a rat model of RA. METHOD: Rheumatoid arthritis was induced in rats by Freund Complete Adjuvant (FCA; 1 mg/0.1 ml paraffin oil, subcutaneously) on days (0, 30 and 40). Etanercept was administered subcutaneously at a dose of (0.3 mg/kg 3 times/week). Arthritis parameters, erythrocytic indices, iron profile, serum TNF-α, serum IL-6 and hepatic RT-PCR hepcidin expression were assessed. RESULTS: FCA-rats developed arthritis and anemia, with significant increase of serum TNFα and IL-6 levels, and of hepcidin gene expression. In RA-rats, etanercept administration improved arthritis, corrected the erythrocyte indices and restored serum iron and ferritin with significant reduction in TNF-α, IL-6 and hepcidin gene expression. Hepcidin expression was negatively correlated to erythrocytic indices and iron profile, while it was positively correlated to serum TNF-α and IL-6 levels. CONCLUSION: Etanercept improved anemia in this animal model of RA, which could be explained in part by the reduction in hepcidin gene expression.


Assuntos
Anemia/tratamento farmacológico , Artrite Reumatoide/tratamento farmacológico , Etanercepte/uso terapêutico , Expressão Gênica/efeitos dos fármacos , Hepcidinas/genética , Anemia/sangue , Anemia/etiologia , Animais , Artrite Reumatoide/sangue , Artrite Reumatoide/complicações , Citocinas/sangue , Modelos Animais de Doenças , Ferritinas/sangue , Adjuvante de Freund , Hemoglobinas/análise , Masculino , Ratos Wistar
15.
Reumatismo ; 71(1): 24-30, 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-30932440

RESUMO

We performed a retrospective analysis to evaluate the survival on first line biologic drug of rheumatoid arthritis (RA) patients with potential occult HBV infection (pOBI). We analysed longitudinal data of 486 consecutive RA patients starting a first biological drug in a time frame from 1st January 2008 to 31st December 2014. Demographic and disease related characteristics were collected at baseline and at the last observation visit. Baseline serological markers of HBV infection and causes of treatment discontinuation were also recorded. Primary endpoint was the influence of pOBI on drug survival, estimated by Kaplan-Meier life table analysis. Estimates hazard ratios (HRs) of drug discontinuation, adjusted for disease characteristics, biological drug class and HBcAb status were computed by Cox-regression models. The retention rate was significantly lower in pOBI positive patients (58.2%) when compared to pOBI negative ones (67.8%) and this data was confirmed also when only discontinuation due to ineffectiveness was considered (pOBI positive 66.4% vs pOBI negative 75.3%, long rank 7.93, p=0.005). Cox regression models showed a significant association between HBcAb-neg (HR 0.58, 0.41-0.84), higher ESR-DAS28 at baseline (HR 1.07, 1.03-1.11) or RF/ACPA-neg (HR 1.46, 1.04-2.06) and drug discontinuation. Occult HBV infection seems to influence negatively the effectiveness of biological therapies in RA patients.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Hepatite B/complicações , Imunossupressores/uso terapêutico , Adesão à Medicação/estatística & dados numéricos , Abatacepte/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Citrulinação , DNA Viral/sangue , Etanercepte/uso terapêutico , Feminino , Glucocorticoides/uso terapêutico , Antígenos do Núcleo do Vírus da Hepatite B/sangue , Vírus da Hepatite B/genética , Vírus da Hepatite B/imunologia , Humanos , Estimativa de Kaplan-Meier , Masculino , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Sistema de Registros , Estudos Retrospectivos
16.
BioDrugs ; 33(3): 299-306, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30945206

RESUMO

BACKGROUND: Diverging approaches towards market entry and uptake of biosimilars, even within a country, leads to regional variation in biosimilar use. This is the case in Sweden, where the 21 county councils control the healthcare budget and offer regional guidance. OBJECTIVES: This study aimed to analyse the market dynamics of originator and biosimilar etanercept (outpatient setting) in the different counties of Sweden, and examine the influence of local policy measures and practices, in addition to national policy. METHODS: This study was performed in three steps: (1) a structured review of the literature on (biosimilar) policies in Sweden; (2) analysis of market data on the counties' originator and biosimilar etanercept uptake (quarter two 2012 to quarter four 2017) provided by IQVIA™; and (3) discussion of findings in face-to-face semi-structured interviews with the national pricing and reimbursement agency, key experts in the county councils of Skåne, Västra Götaland and Stockholm, and an industry representative. RESULTS: Notwithstanding the existence of a national managed entry agreement for etanercept, wide variations in biosimilar market shares between counties were observed (40-82% in 2017). Over time, early and late adopters of biosimilar etanercept can be distinguished. In quarter four 2017, biosimilar market shares of all counties slightly decreased in accordance with the lower priced originator product from 1 October 2017. As prescriptions for treatment with etanercept are often provided for a year, two approaches are possible to switch patients: active pullback of prescriptions resulting in additional workload, or wait until the patient's next visit. Qualitative analysis indicated that the choice to use the biosimilar or the originator product depends on differences in rebated prices of the biosimilar and originator product, the presence of key opinion leaders, local guidelines, and financial streams and local gainsharing arrangements. Our estimates of current rebated prices and costs after gainsharing for the county councils and Government reveal only limited price differences between products. CONCLUSIONS: Regional variations in use of biosimilar etanercept can be seen although prices are coordinated nationally. This suggests that counties react differently to price differences and highlights the role of local policy and attitudes of stakeholders towards biosimilars and switching. It seems that some counties are hesitant to switch patients, as it is associated with an increased administrative workload that might not be compensated for by savings associated with a lower priced product.


Assuntos
Medicamentos Biossimilares/uso terapêutico , Indústria Farmacêutica/legislação & jurisprudência , Marketing/legislação & jurisprudência , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/economia , Medicamentos Biossimilares/economia , Custos de Medicamentos , Indústria Farmacêutica/economia , Etanercepte/economia , Etanercepte/uso terapêutico , Humanos , Marketing/economia , Pacientes Ambulatoriais , Suécia
17.
J Colloid Interface Sci ; 549: 50-62, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31015056

RESUMO

Spinal cord injury (SCI) can cause locomotor dysfunctions and sensory deficits. Evidence shows that functional nanodrugs can regulate macrophage polarization and promote anti-inflammatory cytokine expression, which is feasible in SCI immunotherapeutic treatments. Molybdenum disulfide (MoS2) nanomaterials have garnered great attention as potential carriers for therapeutic payload. Herein, we synthesize MoS2@PEG (MoS2 = molybdenum disulfide, PEG = poly (ethylene glycol)) nanoflowers as an effective carrier for loading etanercept (ET) to treat SCI. We characterize drug loading and release properties of MoS2@PEG in vitro and demonstrate that ET-loading MoS2@PEG obviously inhibits the expression of M1-related pro-inflammatory markers (TNF-α, CD86 and iNOS), while promoting M2-related anti-inflammatory markers (Agr1, CD206 and IL-10) levels. In vivo, the mouse model of SCI shows that long-circulating ET-MoS2@PEG nanodrugs can effectively extravasate into the injured spinal cord up to 96 h after SCI, and promote macrophages towards M2 type polarization. As a result, the ET-loading MoS2@PEG administration in mice can protect survival motor neurons, thus, reducing injured areas at central lesion sites, and significantly improving locomotor recovery. This study demonstrates the anti-inflammatory and neuroprotective activities of ET-MoS2@PEG and promising utility of MoS2 nanomaterial-mediated drug delivery.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Dissulfetos/química , Etanercepte/farmacologia , Macrófagos/efeitos dos fármacos , Nanopartículas Metálicas/química , Molibdênio/química , Traumatismos da Medula Espinal/tratamento farmacológico , Animais , Anti-Inflamatórios não Esteroides/uso terapêutico , Sobrevivência Celular/efeitos dos fármacos , Citocinas/metabolismo , Portadores de Fármacos , Liberação Controlada de Fármacos , Etanercepte/uso terapêutico , Feminino , Humanos , Interleucina-10/metabolismo , Macrófagos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Neurônios Motores/efeitos dos fármacos , Neurônios Motores/patologia , Óxido Nítrico Sintase Tipo II/metabolismo , Tamanho da Partícula , Permeabilidade , Polietilenoglicóis , Células RAW 264.7 , Medula Espinal/efeitos dos fármacos , Medula Espinal/metabolismo , Medula Espinal/patologia , Propriedades de Superfície
19.
Dermatol Online J ; 25(2)2019 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-30865417

RESUMO

Acrodermatitis continua of Hallopeau, first described in 1890, is an uncommon variant of pustular psoriasis. It presents as a sterile pustular eruption of the tips of fingers and toes. The condition has a chronic, relapsing course and is often resistant to many anti-psoriatic therapies. In the following case, we present our experience of etanercept use in a 61-year-old man. Although initial therapy with high-dose etanercept achieved a rapid, sustained response and remission, the lesions relapsed a few months into a lower, maintenance dosage. This result prompted the use a second biotherapeutic agent ustekinumab, which resulted in complete remission, but required a higher dosage than recommended with reduced dosing intervals.


Assuntos
Acrodermatite/tratamento farmacológico , Fármacos Dermatológicos/uso terapêutico , Etanercepte/uso terapêutico , Psoríase/tratamento farmacológico , Ustekinumab/uso terapêutico , Acrodermatite/etiologia , Produtos Biológicos/uso terapêutico , Fármacos Dermatológicos/administração & dosagem , Etanercepte/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Psoríase/complicações , Recidiva , Ustekinumab/administração & dosagem
20.
Am J Clin Dermatol ; 20(3): 409-422, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30895525

RESUMO

Sarcoidosis is an inflammatory disease defined by the presence of non-caseating granulomas. It can affect a number of organ systems, most commonly the lungs, lymph nodes, and skin. Cutaneous manifestations of sarcoidosis can impose a significant detriment to patients' quality of life. The accepted first-line therapy for cutaneous sarcoidosis consists of intralesional and oral corticosteroids, but these can fail in the face of resistant disease and corticosteroid-induced adverse effects. Second-line agents include tetracyclines, hydroxychloroquine, and methotrexate. Biologics are an emerging treatment option for the management of cutaneous sarcoidosis, but their role in management is not well-defined. In this article, we reviewed the currently available English-language publications on the use of biologics in managing cutaneous sarcoidosis. Although somewhat limited, the data in published studies support the use of both infliximab and adalimumab as third-line treatments for chronic or resistant cutaneous sarcoidosis. There were also scattered reports of etanercept, rituximab, golimumab, and ustekinumab being utilized as third-line agents with varying degrees of success. Larger and more extensive investigations are required to further assess the adverse effect profile and optimal dosing for managing cutaneous sarcoidosis.


Assuntos
Anti-Inflamatórios/uso terapêutico , Produtos Biológicos/uso terapêutico , Glucocorticoides/farmacologia , Sarcoidose/tratamento farmacológico , Dermatopatias/tratamento farmacológico , Adalimumab/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Produtos Biológicos/farmacologia , Resistência a Medicamentos , Etanercepte/uso terapêutico , Glucocorticoides/uso terapêutico , Infliximab/uso terapêutico , Uso Off-Label , Sarcoidose/imunologia , Sarcoidose/patologia , Dermatopatias/imunologia , Dermatopatias/patologia , Resultado do Tratamento
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