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1.
J Drugs Dermatol ; 20(1): 115-114, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33400405

RESUMO

The COVID-19 pandemic has forced healthcare providers across all specialties to adjust their methods of clinical practice. In Dermatology, focus on the continued safe usage of immunomodulating biologic therapies has attracted particular interest as the COVID-19 virus represents a novel infection risk. While guidance on biologic initiation and continuation has been established,1 the return to normalcy will likely involve a safe and effective vaccine. This vaccine(s) will represent a new clinical hurdle for prescribers who have continued patients on biologic therapy throughout the pandemic.


Assuntos
Produtos Biológicos/administração & dosagem , /prevenção & controle , /epidemiologia , Pessoal de Saúde/tendências , Humanos
3.
Medicine (Baltimore) ; 99(52): e23861, 2020 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-33350780

RESUMO

ABSTRACT: We examined whether the age of patients with rheumatoid arthritis was associated with adverse events (AEs) caused by biologic disease-modifying antirheumatic drugs (bDMARDs).Patients with rheumatoid arthritis using bDMARDs from Showa University Hospital, Showa University Northern Yokohama Hospital, and Showa University Koto Toyosu Hospital from January 2005 to December 2017 were eligible for this retrospective cohort study. The maximum observation period was determined to be 1 year. Outcomes in patients older and younger than 75 years were compared. The primary outcome was the rate of drug discontinuation because of AEs caused by bDMARDs. Univariate and multivariate analyses were performed using Pearson's chi-squared test and logistic regression analysis, respectively.A total of 416 patients were enrolled; median (interquartile range [IQR]): 60.0 (44.3 - 71.0) years and 84.6% women; patients ≥ 75 years were 67/416 (16.1%). The rates of drug discontinuation because of AEs caused by bDMARDs were 10.5% (7/67) in patients 75 years and older and 10.9% (38/349) in those younger than 75 years (relative risk 0.95, 95% confidential interval 0.45-2.24). In logistic regression analysis adjusted for covariates, the rate of drug discontinuation showed no significant difference between the patients ≥ 75 years and the those < 75 years (adjusted odds ratio 0.70, 95% confidential interval 0.29-1.75, P = .45).The rate of drug discontinuation because of AEs caused by bDMARDs was not significantly different between patients 75 years and older and patients younger than 75 years.


Assuntos
Antirreumáticos/efeitos adversos , Artrite Reumatoide , Produtos Biológicos/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Suspensão de Tratamento/estatística & dados numéricos , Fatores Etários , Idoso , Antirreumáticos/administração & dosagem , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/epidemiologia , Produtos Biológicos/administração & dosagem , Estudos de Coortes , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/diagnóstico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Feminino , Humanos , Japão/epidemiologia , Masculino , Estudos Retrospectivos , Medição de Risco
4.
Dermatol Ther ; 33(6): e14516, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33169500

RESUMO

Since the onset of the coronavirus disease 2019 (COVID-19) pandemic, there has been an open debate on the impact of biological drugs used in the treatment of psoriasis. To define whether patients under treatment with biologics suffer from increased morbidity and mortality from COVID-19, compared to psoriatic patients treated only with topical drugs, we designed an observational monocentric prevalence study recording the personal and clinical data of psoriatic patients, with focus on the presentation of signs and symptoms related to COVID-19 in the period of time ranging from 1 January 2020 to 31 May 2020. A total of 180 patients were enrolled into two groups: 100 patients in the topical therapy group and 80 patients in the biological therapy group. No statistically significant difference was found between the groups regarding the prevalence of COVID-19 infection and symptoms at a bivariable analysis with adjustment for confounders. In conclusion, psoriatic patients under treatment with biologics do not seem to be more susceptible to COVID-19 compared to other psoriatic patients and we suggest not interrupting treatment with biological drugs, even in areas suffering from active outbreaks of the disease.


Assuntos
Produtos Biológicos/administração & dosagem , Fármacos Dermatológicos/administração & dosagem , Imunossupressores/administração & dosagem , Psoríase/tratamento farmacológico , Adulto , Idoso , Produtos Biológicos/efeitos adversos , Fármacos Dermatológicos/efeitos adversos , Esquema de Medicação , Feminino , Humanos , Hospedeiro Imunocomprometido , Imunossupressores/efeitos adversos , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Prospectivos , Psoríase/epidemiologia , Psoríase/imunologia , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
5.
Am J Gastroenterol ; 115(11): 1768-1774, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33156094

RESUMO

INTRODUCTION: De-escalation of biologic therapy is a commonly encountered clinical scenario. Although biologic discontinuation has been associated with high rates of relapse, the effectiveness of dose de-escalation is unclear. This review was performed to determine the effectiveness of dose de-escalation of biologic therapy in inflammatory bowel disease. METHODS: We searched EMBASE, MEDLINE, and the Cochrane Central Register of Controlled Trials from inception to October 2019. Randomized controlled trials and observational studies involving dose de-escalation of biologic therapy in adults with inflammatory bowel disease in remission were included. Studies involving biologic discontinuation only and those lacking outcomes after dose de-escalation were excluded. Risk of bias was assessed using the Newcastle-Ottawa Scale. RESULTS: We identified 1,537 unique citations with 20 eligible studies after full-text review. A total of 995 patients were included from 18 observational studies (4 prospective and 14 retrospective), 1 nonrandomized controlled trial, and 1 subgroup analysis of a randomized controlled trial. Seven studies included patients with Crohn's disease, 1 included patients with ulcerative colitis, and 12 included both. Overall, clinical relapse occurred in 0%-54% of patients who dose de-escalated biologic therapy (17 studies). The 1-year rate of clinical relapse ranged from 7% to 50% (6 studies). Eighteen studies were considered at high risk of bias, mostly because of the lack of a control group. DISCUSSION: Dose de-escalation seems to be associated with high rates of clinical relapse; however, the quality of the evidence was very low. Additional controlled prospective studies are needed to clarify the effectiveness of biologic de-escalation and identify predictors of success.


Assuntos
Produtos Biológicos/administração & dosagem , Colite Ulcerativa/tratamento farmacológico , Doença de Crohn/tratamento farmacológico , Fármacos Gastrointestinais/administração & dosagem , Doenças Inflamatórias Intestinais/tratamento farmacológico , Inibidores do Fator de Necrose Tumoral/administração & dosagem , Adalimumab/administração & dosagem , Anticorpos Monoclonais Humanizados/administração & dosagem , Colite Ulcerativa/fisiopatologia , Doença de Crohn/fisiopatologia , Humanos , Doenças Inflamatórias Intestinais/fisiopatologia , Infliximab/administração & dosagem , Recidiva
6.
Yakugaku Zasshi ; 140(11): 1305-1312, 2020.
Artigo em Japonês | MEDLINE | ID: mdl-33132265

RESUMO

Recently, biologics including peptides, proteins, antibodies, and nucleic acids have attracted interest as drug candidates for new modalities, since these compounds can act on target molecules that are not be affected by conventional drugs with a small molecular weight to promote greater selectivity, potency, and safety. Generally, to administer biologics, parenteral routes like intravenous and intramuscular injections have been mainly selected due to their poor oral absorbability and stability in the gastrointestinal tract, which can adversely affect patient compliance. Depending on the target diseases, inhalable formulations can be used to achieve both topical effects in the respiratory tracts and systemic actions due to the characteristics of the pulmonary site, including a large surface area, abundant capillary network, thin membrane with adequate permeability for macromolecules, reduced enzymatic degradation, and a lack of first-pass metabolism. In this study, to achieve desirable delivery of peptide drugs with an inhalable formulation to target sites in the respiratory tract and/or absorption sites in the lung, peptide-loaded inhalable formulations were designed by the application of flash nanoprecipitation, one of the precipitation methods to prepare functional nanoparticles, and the fine droplet drying process, a powderization technique using printing technology, to control the pharmacokinetic behavior. From the findings of the study, the strategic applications of these techniques could contribute to provide peptide-loaded inhalable formulations to enhance their biopharmaceutical potentials.


Assuntos
Produtos Biológicos/administração & dosagem , Produtos Biológicos/farmacocinética , Composição de Medicamentos/métodos , Sistemas de Liberação de Medicamentos , Desenho de Fármacos , Peptídeos/administração & dosagem , Peptídeos/farmacocinética , Precipitação Química , Inaladores de Pó Seco , Nanopartículas
7.
Drugs ; 80(18): 1929-1946, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33068263

RESUMO

BACKGROUND: Based on current evidence, recent guidelines of the National Institute of Health, USA indicated the use of remdesivir and dexamethasone for the treatment of COVID-19 patients with mild-moderate disease, not requiring high-flow oxygen. No therapeutic agent directed against the immunologic pathogenic mechanisms related to the cytokine release syndrome complicating the disease was indicated. OBJECTIVES: The purpose of this review was to assess the clinical impact of different therapies for COVID-19; thus, helping to identify the optimal management of the disease. To explain the rationale for the different therapeutic approaches, the characteristics of SARS-CoV-2, the pathogenesis of COVID-19, and the immune response triggered by SARS-CoV-2 infection were reported. METHODS: The efficacy assessment of the different treatments was performed by a systematic review in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Available English language published articles including randomised controlled trials, open-label trials of antivirals and immune therapies extracted from Medline, Google Scholar, and MedRxiv databases were analysed. For inclusion, the primary end point of the trials had to be the efficacy as measured by the improvement of clinical features, or mortality, or the Intensive Care Unit Admission rate, or the discharge number. Case reports, paediatric studies, and studies without control group were excluded. The literature search was extended up to August 15, 2020. RESULTS: After the removal of duplicate articles, and the exclusion of studies not meeting the eligibility criteria, 2 trials of lopinavir/ritonavir, 1 of favipiravir, 3 of remdesivir, 1 of dexamethasone, 3 of hydroxychloroquine, 2 of colchicine, 6 of tocilizumab, 1 of sarilumab, 1 of siltuximab, 2 of anakinra, 3 of baricitinib, 1 of ruxolitinib, 1 of mavrilimumab, and 1 of itolizumab were suitable for the review. Among antivirals, only remdesivir significantly reduced the time to recovery, and mortality. Data for chloroquine and hydroxychloroquine were largely inconclusive. In a large trial, dexamethasone 6 mg/day reduced mortality by one-third. Trials of tocilizumab and sarilumab did not definitively demonstrate efficacy. Anakinra significantly reduced the mortality in 2 trials. Three retrospective trials on a cumulative number of 145 patients, reported the efficacy of baricitinib, with significant reduction of intensive care unit admission, and deaths. These results were recently confirmed by the ACTT-2 trial. Due to paucity of studies and to the small size clinical series, the results of other immune therapies were not conclusive. CONCLUSIONS: Beyond the supportive therapy, up to now the best therapeutic approach for COVID-19 may be a three-step combination therapy, including remdesivir 100 mg/day (200 mg loading dose on first day) in the first stage of the disease, and combined dexamethasone 6 mg/day plus baricitinib 4 mg/day to target the immune dysregulation triggered by the SARS-CoV-2 infection. The promising results of anakinra should be confirmed by the ongoing RCTs.


Assuntos
Anti-Inflamatórios/uso terapêutico , Antivirais/uso terapêutico , Produtos Biológicos/uso terapêutico , /tratamento farmacológico , Monofosfato de Adenosina/análogos & derivados , Monofosfato de Adenosina/uso terapêutico , Alanina/análogos & derivados , Alanina/uso terapêutico , Anti-Inflamatórios/administração & dosagem , Anticorpos Monoclonais Humanizados , Antivirais/administração & dosagem , Produtos Biológicos/administração & dosagem , Citocinas/efeitos dos fármacos , Citocinas/metabolismo , Dexametasona/uso terapêutico , Quimioterapia Combinada , Humanos , Mediadores da Inflamação/metabolismo , Unidades de Terapia Intensiva , Pandemias , Estudos Retrospectivos
8.
Dis Colon Rectum ; 63(11): 1524-1533, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33044293

RESUMO

BACKGROUND: Existing studies on the effects of biological medications on surgical complications among patients with ulcerative colitis have mixed results. Because biologicals may hinder response to infections and wound healing, preoperative exposure may increase postoperative complications. OBJECTIVE: The purpose of this study was to evaluate associations between biological exposure within 6 months preceding colectomy or proctocolectomy and postoperative complications among patients with ulcerative colitis. DESIGN: This was a retrospective cohort study with multivariate regression analysis after coarsened exact matching. SETTINGS: A large commercial insurance claims database (2003-2016) was used. PATIENTS: A total of 1794 patients with ulcerative colitis underwent total abdominal colectomy with end ileostomy, total proctocolectomy with end ileostomy, or total proctocolectomy with IPAA. Twenty-two percent were exposed to biologicals in the 6 months preceding surgery. MAIN OUTCOMES MEASURES: Healthcare use (length of stay, unplanned reoperation/procedure, emergency department visit, or readmission) and complications (infectious, hernia or wound disruption, thromboembolic, or cardiopulmonary) within 30 postoperative days were measured. RESULTS: Exposure to biological medications was associated with shorter surgical hospitalization (7 vs 8 d; p <0.001) but otherwise was not associated with differences in healthcare use or postoperative complications. PATIENTS: who underwent total proctocolectomy with IPAA had higher odds of infectious complications compared with those who underwent total abdominal colectomy with end ileostomy (adjusted OR = 2.2 (95% CI, 1.5-3.0); p < 0.001) but had lower odds of cardiopulmonary complications (adjusted OR = 0.4 (95% CI, 0.3-0.6); p < 0.001). LIMITATIONS: Analysis of private insurance database claims data may not represent uninsured or government-insured patients and may be limited by coding accuracy. Matched cohorts differed in age and Charlson Comorbidity Index, which could be influential even after multivariate adjustments. CONCLUSIONS: Biological exposure among patients with ulcerative colitis is not associated with higher odds of postoperative complications or healthcare resource use. These data, in combination with clinical judgment and patient preferences, may aid in complex decision-making regarding operative timing, operation type, and perioperative medication management. See Video Abstract at http://links.lww.com/DCR/B370. EL USO DE MEDICAMENTOS BIOLÓGICOS NO AUMENTA LAS COMPLICACIONES POSTOPERATORIAS ENTRE PACIENTES CON COLITIS ULCERATIVA SOMETIDOS A UNA COLECTOMÍA: UN ANÁLISIS DE COHORTE RETROSPECTIVO DE PACIENTES CON SEGURO PRIVADO: Estudios existentes sobre los efectos de medicamentos biológicos, en complicaciones quirúrgicas, en pacientes con colitis ulcerativa, presentan resultados mixtos. Debido a que los productos biológicos pueden retrasar la respuesta a las infecciones y curación de heridas, su exposición preoperatoria pueden aumentar las complicaciones postoperatorias.Evaluar las asociaciones entre la exposición biológica dentro de los seis meses anteriores a la colectomía o proctocolectomía y las complicaciones postoperatorias entre los pacientes con colitis ulcerativa.Estudio de cohorte retrospectivo con análisis de regresión multivariante después de una coincidencia exacta aproximada.Una gran base de datos de reclamaciones de seguros comerciales (2003-2016).Un total de 1.794 pacientes con colitis ulcerativa, se sometieron a colectomía abdominal total con ileostomía terminal, proctocolectomía total con ileostomía terminal o proctocolectomía total con anastomosis anal y bolsa ileal. 22% estuvieron expuestos a productos biológicos, seis meses antes de la cirugía.Utilización de la atención médica (duración de la estadía, reoperación o procedimiento no planificado, visita al servicio de urgencias o reingreso) y complicaciones (infecciosas, hernias o dehiscencias de heridas, tromboembólicas o cardiopulmonares) dentro de los 30 días postoperatorios.La exposición a medicamentos biológicos se asoció con una hospitalización quirúrgica más corta (7 frente a 8 días, p <0,001), pero por lo demás, no se asoció con diferencias en la utilización de la atención médica o complicaciones postoperatorias. Los pacientes que se sometieron a proctocolectomía total con anastomosis anal y bolsa ileal, tuvieron mayores probabilidades de complicaciones infecciosas, en comparación con aquellos que se sometieron a colectomía abdominal total con ileostomía final (aOR 2.2, IC 95% [1.5-3.0], p <0.001) pero tuvieron menores probabilidades de complicaciones cardiopulmonares (aOR 0.4, IC 95% [0.3-0.6], p <0.001).El análisis de los datos de reclamaciones, de la base de datos de los seguros privados, puede no representar a pacientes no asegurados o asegurados por el gobierno, y puede estar limitado por la precisión de la codificación. Las cohortes emparejadas diferían en la edad y el índice de comorbilidad de Charlson, lo que podría influir incluso después de ajustes multivariados.La exposición biológica entre los pacientes con colitis ulcerativa, no se asocia con mayores probabilidades de complicaciones postoperatorias, o a la utilización de recursos sanitarios. Estos datos, en combinación con el juicio clínico y las preferencias del paciente, pueden ayudar en la toma de decisiones complejas con respecto al momento quirúrgico, el tipo de operación y el manejo de la medicación perioperatoria. Consulte Video Resumen en http://links.lww.com/DCR/B370. (Traducción-Dr Fidel Ruiz Healy).


Assuntos
Produtos Biológicos , Colite Ulcerativa , Ileostomia , Complicações Pós-Operatórias , Proctocolectomia Restauradora , Produtos Biológicos/administração & dosagem , Produtos Biológicos/efeitos adversos , Tomada de Decisão Clínica/métodos , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/cirurgia , Feminino , Humanos , Ileostomia/efeitos adversos , Ileostomia/métodos , Revisão da Utilização de Seguros , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Avaliação de Processos e Resultados em Cuidados de Saúde , Preferência do Paciente/estatística & dados numéricos , Readmissão do Paciente/estatística & dados numéricos , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Proctocolectomia Restauradora/efeitos adversos , Proctocolectomia Restauradora/métodos , Estudos Retrospectivos , Estados Unidos
9.
Pediatrics ; 146(5)2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33060258

RESUMO

BACKGROUND: Exogenous surfactants to treat respiratory distress syndrome (RDS) are approved for tracheal instillation only; this requires intubation, often followed by positive pressure ventilation to promote distribution. Aerosol delivery offers a safer alternative, but clinical studies have had mixed results. We hypothesized that efficient aerosolization of a surfactant with low viscosity, early in the course of RDS, could reduce the need for intubation and instillation of liquid surfactant. METHODS: A prospective, multicenter, randomized, unblinded comparison trial of aerosolized calfactant (Infasurf) in newborns with signs of RDS that required noninvasive respiratory support. Calfactant was aerosolized by using a Solarys nebulizer modified with a pacifier adapter; 6 mL/kg (210 mg phospholipid/kg body weight) were delivered directly into the mouth. Infants in the aerosol group received up to 3 treatments, at least 4 hours apart. Infants in the control group received usual care, determined by providers. Infants were intubated and given instilled surfactant for persistent or worsening respiratory distress, at their providers' discretion. RESULTS: Among 22 NICUs, 457 infants were enrolled; gestation 23 to 41 (median 33) weeks and birth weight 595 to 4802 (median 1960) grams. In total, 230 infants were randomly assigned to aerosol; 225 received 334 treatments, starting at a median of 5 hours. The rates of intubation for surfactant instillation were 26% in the aerosol group and 50% in the usual care group (P < .0001). Respiratory outcomes up to 28 days of age were no different. CONCLUSIONS: In newborns with early, mild to moderate respiratory distress, aerosolized calfactant at a dose of 210 mg phospholipid/kg body weight reduced intubation and surfactant instillation by nearly one-half.


Assuntos
Produtos Biológicos/administração & dosagem , Surfactantes Pulmonares/administração & dosagem , Síndrome do Desconforto Respiratório do Recém-Nascido/tratamento farmacológico , Administração Oral , Aerossóis , Estudos de Coortes , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Unidades de Terapia Intensiva Neonatal/estatística & dados numéricos , Intubação Intratraqueal/estatística & dados numéricos , Masculino , Nebulizadores e Vaporizadores , Estudos Prospectivos
10.
J Drugs Dermatol ; 19(9): 889-892, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-33026746

RESUMO

Early December 2019 witnessed an international outbreak of a novel coronavirus (COVID 19) designated severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2). Since then, a number of therapeutic molecules have been explored to have potential efficacy against the SARS-Cov-2 per se or its sequelae. There are no Food and Drug Administration specific therapies approved so far; however, numerous drugs based on varying levels of evidence, in vitro studies and compassionate drug trials are being established as therapeutic agents, especially drugs approved for previous emergence of the severe acute respiratory syndrome (SARS-CoV-1) and Middle east respiratory syndrome coronavirus (MERS-Cov). Numerous active clinical trials for COVID-19 with more than 150 drugs and products are under study. Needless to say, many dermatological drugs are being employed to mitigate this pandemic threat. We aim to review drugs with potential against SARS-Cov-2 widely used in dermatology practice. Additionally, rampant and overzealous use of these drugs as well as introduction of new molecules might lead to emergence of adverse effects associated with these agents. Dermatologists must be on lookout for any cutaneous adverse effects of these drugs. J Drugs Dermatol. 2020;19(9):889-892. doi:10.36849/JDD.2020.5323.


Assuntos
Antivirais/efeitos adversos , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/epidemiologia , Fármacos Dermatológicos/efeitos adversos , Erupção por Droga/etiologia , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/epidemiologia , Síndrome Respiratória Aguda Grave/tratamento farmacológico , Monofosfato de Adenosina/administração & dosagem , Monofosfato de Adenosina/efeitos adversos , Monofosfato de Adenosina/análogos & derivados , Alanina/administração & dosagem , Alanina/efeitos adversos , Alanina/análogos & derivados , Antivirais/uso terapêutico , Produtos Biológicos/administração & dosagem , Produtos Biológicos/efeitos adversos , Fármacos Dermatológicos/uso terapêutico , Erupção por Droga/epidemiologia , Erupção por Droga/fisiopatologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Feminino , Humanos , Incidência , Masculino , Pandemias , Prognóstico , Medição de Risco , Síndrome Respiratória Aguda Grave/diagnóstico , Síndrome Respiratória Aguda Grave/epidemiologia
11.
Reumatol. clín. (Barc.) ; 16(5,pt.1): 319-323, sept.-oct. 2020. tab
Artigo em Inglês | IBECS | ID: ibc-195887

RESUMO

OBJECTIVE: To describe practice patterns, long-term outcome, and related factors, in relation to biological therapies tapering in rheumatoid arthritis (RA) patients in a well-controlled real-world setting. METHODS: An observational longitudinal retrospective 10-year study was conducted in all RA patients receiving biological agents in an RA clinic from May 2003 to October 2013. Biological treatment of patients with sustained DAS28<3.2 or SDAI<11 was tapered (dose down-titrated or interval widen) or discontinued as per practice protocol. Primary outcome of tapering was relapse, defined as an increase in DAS28≥1.2. Descriptive, survival analysis, and logistic regression analysis with first relapse as dependent variable were carried out. RESULTS: Of 193 RA patients on biological treatment (mean age 54±14 years, 81% women), tapering was applied in 106 (55%) and discontinuation in 34 (17.6%). During follow-up 38 patients relapsed (62%). Rate of relapse was 10% at 6 months, 19% at 12 months, 33.2% at 2 years and 50% after 5 years. Mean time in dose reduction was 4.5 years [95% confidence interval (95% CI): 3.7-5.3]. Six patients (15.7%) did not respond after reinstatement of full dose of biologic. In the multivariate analysis, pain [OR=1.26 (95% CI: 1.11-1.43); P<.001] and erythrocyte sedimentation rate (ESR) [OR=1.01 (95% CI: 1.00-1.03); P=.011] at baseline were associated with relapse after tapering. CONCLUSIONS: Tapering may be considered a long-term option in RA patients on biologics and low disease activity, especially if low ESR and pain scores are present at baseline; treatment reinstatement could be considered a safe option in case of relapse


OBJETIVO: Describir los patrones de práctica clínica, los resultados a largo plazo y los factores relacionados en relación a la optimización de las terapias biológicas en pacientes con artritis reumatoide (AR) en un entorno de vida real bien controlado. MÉTODOS: Se realizó un estudio retrospectivo observacional longitudinal de 10 años que incluyó a todos los pacientes con AR que recibieron agentes biológicos en una consulta monográfica de AR entre mayo de 2003 y octubre de 2013. Se optimizó el tratamiento biológico (ajuste de dosis o ampliación de intervalo) en los pacientes con DAS28<3,2 o SDAI<11 de forma mantenida según un protocolo de práctica clínica. La variable principal fue la recaída, definida como un aumento en el DAS28≥1,2. Se realizó un análisis descriptivo, de supervivencia y modelos de regresión logística con la primera recaída como variable dependiente. RESULTADOS: De 193 pacientes con AR en tratamiento biológico (edad media 54±14 años, 81% mujeres), se optimizó la dosis en 106 (55%) y se interrumpió el tratamiento en 34 (17,6%). Durante el seguimiento 38 pacientes recayeron (62%). La tasa de recaída fue del 10% a los 6 meses, del 19% a los 12 meses, del 33,2% a los 2 años y del 50% a los 5 años. El tiempo medio con dosis reducida fue de 4 años y medio (intervalo de confianza del 95% [IC 95%]: 3,7 a 5,3). Seis pacientes (15,7%) no respondieron después de restablecer la dosis completa de biológico. En el análisis multivariado, el dolor (OR=1,26 [IC 95%: 1,11 a 1,43]; p < 0,001) y la velocidad de sedimentación globular (VSG) (OR por mm/h=1,01 [IC 95%: 1,00 a 1,03]; p = 0,011) al inicio del estudio se asociaron a recaída tras la optimización. CONCLUSIONES: La optimización de la dosis se puede considerar una opción a largo plazo en pacientes con AR en tratamiento con agentes biológicos y baja actividad de la enfermedad, especialmente si la VSG y el dolor están en niveles bajos; la reinstauración del tratamiento podría considerarse una opción segura en caso de recaída en la mayoría de los pacientes


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Produtos Biológicos/administração & dosagem , Artrite Reumatoide/tratamento farmacológico , Terapia Biológica , Antirreumáticos/uso terapêutico , Estudos Retrospectivos , Análise de Sobrevida , Antirreumáticos/classificação , Estudos Longitudinais
12.
Urol Clin North Am ; 47(4): 487-510, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33008499

RESUMO

The advent of immunotherapy has revolutionized cancer treatment. Prostate cancer has an immunosuppressive microenvironment and a low tumor mutation burden, resulting in low neoantigen expression. The consensus was that immunotherapy would be less effective in prostate cancer. However, recent studies have reported that prostate cancer does have a high number of DNA damage and repair gene defects. Immunotherapies that have been tested in prostate cancer so far have been mainly vaccines and checkpoint inhibitors. A combination of genomically targeted therapies, with approaches to alleviate immune response and thereby make the tumor microenvironment immunologically hot, is promising.


Assuntos
Produtos Biológicos/administração & dosagem , Vacinas Anticâncer/administração & dosagem , Imunoterapia/métodos , Neoplasias da Próstata/patologia , Neoplasias da Próstata/terapia , Microambiente Tumoral/efeitos dos fármacos , Idoso , Animais , Antígenos de Neoplasias/efeitos dos fármacos , Antígenos de Neoplasias/imunologia , Previsões , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Terapia de Alvo Molecular/métodos , Invasividade Neoplásica/patologia , Metástase Neoplásica/genética , Metástase Neoplásica/imunologia , Estadiamento de Neoplasias , Neoplasias da Próstata/genética , Resultado do Tratamento , Microambiente Tumoral/genética
13.
PLoS One ; 15(9): e0239551, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32946518

RESUMO

Pathway analysis is an informative method for comparing and contrasting drug-induced gene expression in cellular systems. Here, we define the effects of the marine natural product fucoxanthin, separately and in combination with the prototypic phosphatidylinositol 3-kinase (PI3K) inhibitor LY-294002, on gene expression in a well-established human glioblastoma cell system, U87MG. Under conditions which inhibit cell proliferation, LY-294002 and fucoxanthin modulate many pathways in common, including the retinoblastoma, DNA damage, DNA replication and cell cycle pathways. In sharp contrast, we see profound differences in the expression of genes characteristic of pathways such as apoptosis and lipid metabolism, contributing to the development of a differentiated and distinctive drug-induced gene expression signature for each compound. Furthermore, in combination, fucoxanthin synergizes with LY-294002 in inhibiting the growth of U87MG cells, suggesting complementarity in their molecular modes of action and pointing to further treatment combinations. The synergy we observe between the dietary nutraceutical fucoxanthin and the synthetic chemical LY-294002 in producing growth arrest in glioblastoma, illustrates the potential of nutri-pharmaceutical combinations in targeting this challenging disease.


Assuntos
Cromonas/administração & dosagem , Glioblastoma/tratamento farmacológico , Glioblastoma/genética , Morfolinas/administração & dosagem , Xantofilas/administração & dosagem , Apoptose/efeitos dos fármacos , Produtos Biológicos/administração & dosagem , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Terapia Combinada , Suplementos Nutricionais , Sinergismo Farmacológico , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Redes Reguladoras de Genes/efeitos dos fármacos , Glioblastoma/dietoterapia , Humanos , Inibidores de Fosfoinositídeo-3 Quinase/administração & dosagem
14.
Dermatol Ther ; 33(6): e13858, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32686245

RESUMO

Coronavirus disease (COVID-19) is a highly contagious respiratory infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 outbreak has been declared a pandemic by the World Health Organization on March 2020. The pandemic has affected the management of psoriasis not only for those who are under treatment but also for those who are about to begin a new therapy to control their disease. An increasing number of studies in the current literature have focused on the relationship between psoriasis and COVID-19 from different perspectives. This narrative review includes searching the PubMed and Web of Science databases using the keywords "psoriasis," "psoriatic arthritis," "coronavirus," "COVID-19," and "SARS-CoV-2." The search was supplemented by manual searching of reference lists of included articles. A total of 11 relevant original investigations and 6 case studies was identified. The search was updated in May 2019. Due to the absence of randomized controlled trials, it is not likely to have a robust evidence-based approach to psoriasis management in the era of COVID-19. However, the current literature may provide some clues for safety considerations. Conventional immunosuppressive therapies such as methotrexate and cyclosporine, and anti-tumor necrosis factor agents should not be preferred due to increased risk of infection, especially in high-risk areas. The use of cyclosporine may pose additional risk due to the side effect of hypertension, which has been reported to be associated with susceptibility to severe COVID-19. Considering that the current literature has provided no conclusive evidence that biologics increase the risk of COVID-19, withdrawal of these agents should be reserved for patients with COVID-19 symptoms. The treatment approach should be personalized, considering the advantages and disadvantages for each case separately.


Assuntos
Imunossupressores/administração & dosagem , Psoríase/tratamento farmacológico , Produtos Biológicos/administração & dosagem , Produtos Biológicos/efeitos adversos , Fármacos Dermatológicos/administração & dosagem , Fármacos Dermatológicos/efeitos adversos , Humanos , Hipertensão/induzido quimicamente , Hipertensão/complicações , Imunossupressores/efeitos adversos , Fatores de Risco
15.
J Am Acad Dermatol ; 83(5): 1523-1526, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32622891
16.
JAMA Netw Open ; 3(7): e207911, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32725245

RESUMO

Importance: Direct intratumoral delivery of immunotherapies is a compelling approach to overcoming barriers to systemic immunotherapy efficacy. While the use of intratumoral delivery of immunotherapy drugs is increasing rapidly in both the investigational and standard of care domains, the feasibility and safety of these interventions, particularly for deeper lesions that require image-guidance, remain unknown. Objective: To address current knowledge gaps in image-guided techniques for intratumoral immunotherapy delivery and the safety of these interventions. Design, Setting, and Participants: This case series study was performed at a single tertiary cancer center over a 2-year period from January 2016 to January 2018. Patients were followed until January 2019. All patients who underwent image-guided intratumoral delivery of immunotherapy agents in the standard of care, off-label, or investigational setting during the study period were included. Data were analyzed from February 1 to June 1, 2019. Exposures: Image-guided biopsies and intratumoral injections of immunotherapies across several clinical trials as well as standard of care talimogene laherparepvec therapy. Main Outcomes and Measures: Technical success, defined as the delivery of the prescribed injectate volume in its entirety, for image-guided biopsy and injections and procedure-related adverse events. Results: A total of 85 patients (median [interquartile range] age, 61 [47-71] years; 42 [52%] men) underwent 498 encounters during the study period. These encounters comprised 327 image-guided intratumoral investigational agent injections in 67 patients in clinical trials, including 33 patients with melanoma (50%), 14 patients with sarcoma (21%), 3 patients with ovarian cancer (4.5%), 2 patients with breast cancer (3%), and 2 patients with colon cancer (3%). An additional 18 patients with melanoma underwent 113 image-guided talimogene laherparepvec injections. There were no adverse events reported related to the technical component of the procedure, specifically needle insertion or biopsy. Serious adverse events (Common Terminology Criteria for Adverse Events score ≥3), including dyspnea and severe flu-like symptoms developing within 24 hours of the injection and requiring hospitalization, occurred after 3 of 327 investigational agent injections (2%) and 4 of 113 talimogene laherparepvec injections (4%). Conclusions and Relevance: The findings of this case series study suggest that intratumoral injections of immunotherapies were feasible across a range of histological conditions and target organs. Immediate postdelivery anticipated adverse events occurred in a small number of instances. Performing physicians should have the necessary safeguards in place to respond as needed. Optimal methods for intratumoral drug delivery remain unresolved, and efforts to standardize drug delivery techniques are required.


Assuntos
Produtos Biológicos/administração & dosagem , Sistemas de Liberação de Medicamentos/métodos , Imunoterapia/métodos , Injeções Intralesionais , Neoplasias , Idoso , Antineoplásicos Imunológicos/administração & dosagem , Quimioterapia do Câncer por Perfusão Regional , Estudos de Viabilidade , Feminino , Herpesvirus Humano 1 , Humanos , Biópsia Guiada por Imagem/métodos , Injeções Intralesionais/efeitos adversos , Injeções Intralesionais/métodos , Masculino , Pessoa de Meia-Idade , Neoplasias/imunologia , Neoplasias/patologia , Neoplasias/terapia , Avaliação de Processos e Resultados em Cuidados de Saúde
17.
Lancet Child Adolesc Health ; 4(10): 728-739, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32702315

RESUMO

BACKGROUND: Peanut allergy is the leading cause of food-related anaphylaxis. Current management options can negatively affect food allergy-related quality of life. We aimed to investigate the efficacy of an investigational oral biologic drug (AR101). METHODS: The AR101 Trial in Europe Measuring Oral Immunotherapy Success in peanut-allergic children (ARTEMIS) trial was a multicentre, double-blind, randomised, placebo-controlled phase 3 trial done at 18 hospitals in Ireland, France, Germany, Italy, Spain, Sweden, and the UK. Children and adolescents with peanut allergy, aged 4-17 years, who developed dose-limiting symptoms to 300 mg or less peanut protein (equivalent to approximately one peanut kernel) during a double-blind placebo-controlled food challenge test at study entry were enrolled. Participants were randomly assigned (3:1) to receive daily doses of either AR101 oral immunotherapy (AR101 group) or a taste-masked placebo (placebo group). All participants, investigators, and care providers were masked to treatment allocation until the study was completed. Doses were increased every 2 weeks over 6 months until a dose of 300 mg was reached and maintained for 3 months. The primary endpoint was the proportion of participants in the intention-to-treat or safety population (defined as those participants who had been randomly assigned and had received at least one dose of the assigned drug) who could consume a single dose of 1000 mg (cumulative dose 2043 mg) peanut protein without developing dose-limiting allergic symptoms at an exit double-blind placebo-controlled food challenge after 9 months of treatment. Additional endpoints included safety (ie, the frequency and severity of adverse events) and changes in food allergy-related quality of life, assessed by use of age-appropriate Food Allergy Quality of Life Questionnaires (FAQLQs) and the Food Allergy Independent Measure (FAIM). The study is registered with ClinicalTrials.gov, NCT03201003, and is completed. FINDINGS: Between June 12, 2017, and Feb 15, 2018, 227 patients were screened, of whom 175 were randomly assigned to the AR101 group (n=132) and the placebo group (n=43). All primary and secondary endpoints were met. 77 (58%) of 132 participants in the AR101 group tolerated 1000 mg peanut protein at the exit food challenge versus one (2%) of 43 participants in the placebo group (AR101-placebo treatment difference 56·0% [95% CI 44·1-65·2], p<0·0001). Adverse events were reported by almost all participants. The maximum severity of adverse events reported was mild or moderate for most participants who received AR101 (mild, 66 [50%] of 132 participants; moderate, 63 [48%]; and severe, one [1%]) or placebo (mild, 24 [56%] of 43 participants; moderate, 18 [42%]; severe, none). Participants aged 8-12 years in the AR101 group reported improvements that exceeded the minimum clinically important difference between the two groups across all FAQLQ domains. Additionally, participants in the AR101 group and their caregivers reported improvements that exceeded the minimum clinically important difference in FAIM domains related to the perceived likelihood and outcomes of a severe allergic reaction. INTERPRETATION: AR101 oral immunotherapy treatment led to rapid desensitisation to peanut protein, with a predictable safety profile that improved with treatment, and an associated improvement in self-reported and caregiver-reported food allergy-related quality of life. These patient-oriented outcomes provide invaluable data to help physicians, patients, and caregivers make informed, shared decisions on the management of peanut allergy. FUNDING: Aimmune Therapeutics.


Assuntos
Alérgenos/administração & dosagem , Produtos Biológicos/administração & dosagem , Dessensibilização Imunológica/métodos , Hipersensibilidade a Amendoim/terapia , Administração Oral , Adolescente , Criança , Pré-Escolar , Relação Dose-Resposta Imunológica , Método Duplo-Cego , Europa (Continente) , Feminino , Humanos , Masculino , Hipersensibilidade a Amendoim/imunologia , Testes Cutâneos , Resultado do Tratamento
18.
Dermatol Ther ; 33(6): e13867, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32558193

RESUMO

In patients with specific dermatologic disorders who are affected by new corona virus, we know little about disease course (underlying disease and new onset infection), and the most proper management strategies include both issues that are what this systematic review targets. Databases of PubMed, Scopus, Google Scholar, Medscape, and Centre of Evidence-Based Dermatology, coronavirus dermatology resource of Nottingham University searched completely up to May 15, 2020, and initial 237 articles were selected to further review and finally 9 articles (including 12 patients) entered to this study. From 12 patients with chronic underlying dermatologic disease treated with systemic therapies, only 1 patient required Intensive Care Unit admission, the others have been treated for mild-moderate symptoms with conventional therapies. The biologic or immunosuppressive/immunomodulator agents have been ceased during the course of disease. The course of coronovirus diseases 2019 (COVID-19) and its management was as similar as normal populations. Their underlying dermatologic disease were exacerbating from mild to moderate. Their treatment has been continued as before, after the symptoms improved. Exacerbation of patients underlying dermatologic disease was mild to moderate. Discontinuing the treatment in the acute period of COVID and the restart after recovery may prevent severe recurrence and disturbing cytokine storms in these patients.


Assuntos
Produtos Biológicos/administração & dosagem , Fármacos Dermatológicos/administração & dosagem , Imunossupressores/administração & dosagem , Dermatopatias/tratamento farmacológico , Idoso , Produtos Biológicos/efeitos adversos , /imunologia , Doença Crônica , Fármacos Dermatológicos/efeitos adversos , Progressão da Doença , Esquema de Medicação , Medicina Baseada em Evidências , Feminino , Humanos , Hospedeiro Imunocomprometido , Imunossupressores/efeitos adversos , Masculino , Pessoa de Meia-Idade , Recidiva , Medição de Risco , Fatores de Risco , Dermatopatias/diagnóstico , Dermatopatias/imunologia , Resultado do Tratamento
19.
Biochem Pharmacol ; 178: 114123, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32593613

RESUMO

Commonly used drugs for treating many conditions are either natural products or derivatives. In silico modelling has identified several natural products including quercetin as potential highly effective disruptors of the initial infection process involving binding to the interface between the SARS-CoV-2 (Covid-19) Viral Spike Protein and the epithelial cell Angiotensin Converting Enzyme-2 (ACE2) protein. Here we argue that the oral route of administration of quercetin is unlikely to be effective in clinical trials owing to biotransformation during digestion, absorption and metabolism, but suggest that agents could be administered directly by alternative routes such as a nasal or throat spray.


Assuntos
Betacoronavirus/efeitos dos fármacos , Produtos Biológicos/farmacologia , Peptidil Dipeptidase A/metabolismo , Quercetina/farmacologia , Glicoproteína da Espícula de Coronavírus/metabolismo , Betacoronavirus/metabolismo , Betacoronavirus/fisiologia , Produtos Biológicos/administração & dosagem , Produtos Biológicos/química , Ensaios Clínicos como Assunto/métodos , Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/virologia , Avaliação Pré-Clínica de Medicamentos/métodos , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Células Epiteliais/virologia , Interações Hospedeiro-Patógeno/efeitos dos fármacos , Humanos , Estrutura Molecular , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Pneumonia Viral/virologia , Ligação Proteica/efeitos dos fármacos , Quercetina/administração & dosagem , Quercetina/química , Internalização do Vírus/efeitos dos fármacos
20.
Hosp Pract (1995) ; 48(4): 213-222, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32567403

RESUMO

OBJECTIVES: To evaluate the association between biological Disease-Modifying Anti-Rheumatic Drugs (bDMARDs) use and quality of life (QoL) in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS). PATIENTS AND METHODS: We evaluated adult patients prescribed biological DMARDs whose quality of life was evaluated at six and 12 months. The EuroQol 5 dimensions (EQ-5D) was used with the Brazilian tariff. RESULTS: Patients receiving bDMARDs had significant improvements in quality of life after 6 and 12 months (p < 0.001), regardless of the rheumatic condition and the therapeutic regimen (bDMARDs vs bDMARDs plus synthetic DMARDs) (ANCOVA; p > 0.05). At the end of one year, 62.6% of the participants presented significant clinical improvement in QoL. According to a sensitivity analysis, QoL results in the complete case analysis and in the multiple imputation model yielded similar conclusions. Patients with two or more comorbidities and worse QoL and disability status on baseline presented worse QoL at 12 months when compared to those with better disability status on baseline. Baseline clinical disease measured by activity indexes (BASDAI and CDAI) did not influence QoL after 12 months of bDMARD treatment. Pain and malaise were the EQ-5D domain that most influenced quality of life. CONCLUSION: Patients with rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis displayed significantly better QoL levels following treatment with DMARDs.


Assuntos
Antirreumáticos/uso terapêutico , Produtos Biológicos/uso terapêutico , Doenças Reumáticas/tratamento farmacológico , Doenças Reumáticas/psicologia , Adolescente , Adulto , Idoso , Antirreumáticos/administração & dosagem , Antirreumáticos/efeitos adversos , Artrite Psoriásica/tratamento farmacológico , Artrite Psoriásica/psicologia , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/psicologia , Produtos Biológicos/administração & dosagem , Produtos Biológicos/efeitos adversos , Brasil , Comorbidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Qualidade de Vida , Índice de Gravidade de Doença , Fatores Socioeconômicos , Espondilite Anquilosante/tratamento farmacológico , Espondilite Anquilosante/psicologia , Fatores de Tempo , Adulto Jovem
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