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1.
Lancet ; 395(10221): 371-383, 2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-32007172

RESUMO

Asthma is a disease of reversible airflow obstruction characterised clinically by wheezing, shortness of breath, and coughing. Increases in airway type 2 cytokine activity, including interleukin-4 (IL-4), IL-5, and IL-13, are now established biological mechanisms in asthma. Inhaled corticosteroids have been the foundation for asthma treatment, in a large part because they decrease airway type 2 inflammation. However, inhaled or systemic corticosteroids are ineffective treatments in many patients with asthma and few treatment options exist for patients with steroid resistant asthma. Although mechanisms for corticosteroid refractory asthma are likely to be numerous, the development of a new class of biologic agents that target airway type 2 inflammation has provided a new model for treating some patients with corticosteroid refractory asthma. The objective of this Therapeutic paper is to summarise the new type 2 therapeutics, with an emphasis on the biological rationale and clinical efficacy of this new class of asthma therapeutics.


Assuntos
Antiasmáticos/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Asma/tratamento farmacológico , Produtos Biológicos/uso terapêutico , Adulto , Biomarcadores/metabolismo , Ensaios Clínicos Fase III como Assunto , Citocinas/antagonistas & inibidores , Citocinas/fisiologia , Eosinófilos/fisiologia , Previsões , Humanos , Ácidos Indolacéticos/uso terapêutico , Interleucina-4/antagonistas & inibidores , Interleucina-5/antagonistas & inibidores , Omalizumab/uso terapêutico , Piridinas/uso terapêutico , Células Th2/fisiologia , Resultado do Tratamento
3.
Eur J Med Chem ; 181: 111574, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31400705

RESUMO

A series of novel hydroxyethylaminomethylbenzimidazole analogs 5a-y were synthesized and evaluated for their IL-5 inhibitory activity using pro-B Y16 cell line. Among them, 2-(((4-(cyclohexylmethoxy)-1H-benzo[d]imidazol-2-yl)methyl)amino)butan-1-ol (5e, 94.3% inhibition at 30 µM, IC50 = 3.5 µM, cLogP = 4.132) and 3-cyclohexyl-2-(((4-(cyclohexylmethoxy)-1H-benzo[d]imidazol-2-yl)methyl)amino) propan-1-ol (5k, 94.7% inhibition at 30 µM, IC50 = 5.0 µM, cLogP = 6.253) showed the most potent inhibitory activity. The essential feature of SAR (Fig. 5) indicated that the chromenone ring can be replaced by a benzimidazole ring to maintain the inhibitory activity. In addition, the hydroxyethylaminomethyl group was suitable for the IL-5 inhibitory activity. Moreover, the hydrophobic substituents on carbon play an important role in the IL-5 inhibitory activity of these analogs. However, N-substituted analogs did not improve inhibitory activity. In addition, MTT assay of 5e and 5k with normal B lymphoblasts revealed that they had no significant effects on cell viability.


Assuntos
Benzimidazóis/química , Benzimidazóis/farmacologia , Interleucina-5/antagonistas & inibidores , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Humanos , Camundongos , Modelos Moleculares , Relação Estrutura-Atividade
5.
Int J Chron Obstruct Pulmon Dis ; 14: 1045-1051, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31190789

RESUMO

Many patients with chronic obstructive pulmonary disease (COPD) continue to experience exacerbations despite receiving standard-of-care treatments. Novel approaches to COPD treatment focus on understanding and targeting molecular mechanisms of airway inflammation, airway obstruction, remodeling and lung destruction. Several identified phenotypes and endotypes of COPD will pave the future path for a more personalized approach to therapy. Although well known to be associated with neutrophilic inflammation, COPD may also be driven by eosinophilic inflammation both at stable states and during exacerbation. Targeting eosinophilic inflammation has been successful in managing severe eosinophilic asthma and may hold promise in certain phenotypes of COPD. The most promising biologic treatments at an advanced stage of development are agents blocking interleukin (IL)-5 or its receptor. This review examines our current understanding of the eosinophilic inflammation in COPD and the rationale for IL-5 targeting agents.


Assuntos
Anti-Inflamatórios/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Eosinófilos/efeitos dos fármacos , Subunidade alfa de Receptor de Interleucina-5/antagonistas & inibidores , Interleucina-5/antagonistas & inibidores , Pulmão/efeitos dos fármacos , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Animais , Anti-Inflamatórios/efeitos adversos , Anticorpos Monoclonais Humanizados/efeitos adversos , Eosinófilos/metabolismo , Interleucina-5/metabolismo , Subunidade alfa de Receptor de Interleucina-5/metabolismo , Pulmão/metabolismo , Pulmão/fisiopatologia , Terapia de Alvo Molecular , Doença Pulmonar Obstrutiva Crônica/metabolismo , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Transdução de Sinais/efeitos dos fármacos , Resultado do Tratamento
8.
Immunity ; 50(4): 796-811, 2019 04 16.
Artigo em Inglês | MEDLINE | ID: mdl-30995500

RESUMO

The ß common chain cytokines GM-CSF, IL-3, and IL-5 regulate varied inflammatory responses that promote the rapid clearance of pathogens but also contribute to pathology in chronic inflammation. Therapeutic interventions manipulating these cytokines are approved for use in some cancers as well as allergic and autoimmune disease, and others show promising early clinical activity. These approaches are based on our understanding of the inflammatory roles of these cytokines; however, GM-CSF also participates in the resolution of inflammation, and IL-3 and IL-5 may also have such properties. Here, we review the functions of the ß common cytokines in health and disease. We discuss preclinical and clinical data, highlighting the potential inherent in targeting these cytokine pathways, the limitations, and the important gaps in understanding of the basic biology of this cytokine family.


Assuntos
Fator Estimulador de Colônias de Granulócitos e Macrófagos/imunologia , Inflamação/imunologia , Interleucina-3/imunologia , Interleucina-5/imunologia , Animais , Doenças Autoimunes/imunologia , Fator Estimulador de Colônias de Granulócitos e Macrófagos/deficiência , Fator Estimulador de Colônias de Granulócitos e Macrófagos/genética , Fator Estimulador de Colônias de Granulócitos e Macrófagos/uso terapêutico , Hematopoese/imunologia , Humanos , Inflamação/terapia , Interleucina-3/antagonistas & inibidores , Interleucina-3/deficiência , Interleucina-3/genética , Interleucina-5/antagonistas & inibidores , Interleucina-5/deficiência , Interleucina-5/genética , Camundongos , Camundongos Knockout , Família Multigênica , Neoplasias/imunologia , Neoplasias/terapia , Receptores de Fator Estimulador das Colônias de Granulócitos e Macrófagos/genética , Receptores de Fator Estimulador das Colônias de Granulócitos e Macrófagos/imunologia , Receptores de Interleucina-3/genética , Receptores de Interleucina-3/imunologia , Receptores de Interleucina-5/genética , Receptores de Interleucina-5/imunologia , Proteínas Recombinantes/imunologia , Proteínas Recombinantes/uso terapêutico , Transdução de Sinais , Relação Estrutura-Atividade , Vacinação , Cicatrização/imunologia
10.
Allergol Int ; 68(2): 158-166, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30792118

RESUMO

Asthma is a heterogeneous disease with considerable variability noted in disease severity, patterns of airway inflammation, and achievement of disease control on current medications. An absence of disease control is most frequently noted in patients with severe asthma, and is defined as a lack of control while on high dose inhaled corticosteroids (ICS) plus a second controller medication. In part, this lack of control may relate to a diminished effect of current guideline-directed care on the existing pattern of airway inflammation in severe asthma. Airway inflammation in severe asthma has been arbitrarily divided into T (type) 2 high and T2 low. T2 high is characterized by the generation of key cytokines, interleukin (IL)-4, -5 and -13, which generate and regulate airway inflammation. Biomarkers to mark the presence of T2-high inflammation include eosinophils, fractional exhaled nitric oxide (FeNO) and immunoglobulin (Ig) E, whose presence arises from the action of IgE, IL-5, IL-4, and IL-13. In this review, treatment of severe asthma with monoclonal antibodies, i.e. biologics, which are directed against these inflammation generated pathways are reviewed. The available monoclonal antibodies include omalizumab (anti-IgE); mepolizumab, reslizumab and benralizumab (anti-IL-5 pathways), and dupilumab (anti-IL-4/IL-13). The use of these T2-high interventions has led to significant reductions in asthma symptoms, a decreased frequency of exacerbations, and improved lung function in many patients. Not only has the use of these monoclonal antibodies led to improved asthma control in patients with severe disease, their use has provided insight into mechanisms of severe asthma.


Assuntos
Antiasmáticos/uso terapêutico , Asma/tratamento farmacológico , Produtos Biológicos/uso terapêutico , Asma/imunologia , Eosinofilia/tratamento farmacológico , Eosinofilia/imunologia , Humanos , Interleucina-13/antagonistas & inibidores , Interleucina-4/antagonistas & inibidores , Interleucina-5/antagonistas & inibidores
11.
Auris Nasus Larynx ; 46(2): 196-203, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30122651

RESUMO

OBJECTIVE: Eosinophilic otitis media (EOM) is an intractable otitis media characterized by a highly viscous effusion containing eosinophils, and it is mostly associated with bronchial asthma. Recently, anti-IL-5 therapy using mepolizumab has been reported to be effective for patients with severe and refractory eosinophilic bronchial asthma. EOM shows accumulation of eiosinophils in the middle ear effusion and most EOM patients have high numbers of peripheral blood eosinophils. Therefore, we carried out a retrospective study to determine whether anti-IL-5 therapy is also effective in the treatment of EOM. PATIENTS AND METHODS: Nine patients with EOM associated with bronchial asthma received the anti-IL-5 agent mepoliumab as an add-on therapy for at least 6 months (mepolizumab group). They were evaluated by EOM severity scores, symptom scores, bone conduction hearing levels, and surrogate markers before and after receiving the anti-IL-5 therapy. Thirteen EOM patients associated with bronchial asthma who did not receive the anti-IL-5 therapy were also included as controls (control group). RESULTS: The severity scores of most patients in the mepolizumab group were dramatically reduced at 3 months after the initiation of this therapy and, as therapy continued, they further decreased to levels significantly lower than the baseline. However, two patients with a granulation type of EOM showed minimal improvement from the therapy. The severity scores of control patients showed no significant changes during the study period. Significant deterioration of the bone conduction hearing levels was not observed in either group. The number of peripheral blood eosinophils was significantly reduced, and eosinophils were scarcely observed in the middle ear effusion and middle ear mucosa after the mepolizumab therapy. CONCLUSIONS: Anti-IL-5 therapy using mepolizumab was effective at inhibiting eosinophilic recruitment to the middle ear in patients with EOM. However, this therapy showed minimal effect on patients with the granulation type of EOM. Therefore, this therapy may be a viable treatment option for refractory EOM without severe mucosal change.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Asma/tratamento farmacológico , Eosinofilia/tratamento farmacológico , Interleucina-5/antagonistas & inibidores , Otite Média/tratamento farmacológico , Adulto , Idoso , Asma/complicações , Condução Óssea , Orelha Média , Eosinofilia/complicações , Eosinofilia/fisiopatologia , Feminino , Tecido de Granulação , Humanos , Masculino , Pessoa de Meia-Idade , Otite Média/complicações , Otite Média/fisiopatologia , Estudos Retrospectivos , Resultado do Tratamento
12.
J Allergy Clin Immunol ; 143(1): 190-200.e20, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30205189

RESUMO

BACKGROUND: Three anti-IL-5 pathway-directed therapies are approved for use in patients with severe eosinophilic asthma (SEA); however, no head-to-head comparison data are available. OBJECTIVE: We sought to compare the efficacy of licensed doses of mepolizumab, benralizumab, and reslizumab in patients with SEA, according to baseline blood eosinophil counts. METHODS: This indirect treatment comparison (ITC) used data from a Cochrane review and independent searches. Eligible studies were randomized controlled trials in patients aged 12 years or greater with SEA. End points included annualized rate of clinically significant exacerbations and change from baseline in Asthma Control Questionnaire score and FEV1. An ITC was performed in patients with Asthma Control Questionnaire scores of 1.5 or greater and stratified by baseline blood eosinophil count. RESULTS: Eleven studies were included. All treatments significantly reduced the rate of clinically significant exacerbations and improved asthma control versus placebo in all blood eosinophil count subgroups. Mepolizumab reduced clinically significant exacerbations by 34% to 45% versus benralizumab across subgroups (rate ratio ≥400 cells/µL: 0.55 [95% CI, 0.35-0.87]; ≥300 cells/µL: 0.61 [95% CI, 0.37-0.99]; and ≥150 cells/µL: 0.66 [95% CI, 0.49-0.89]; all P < .05) and by 45% versus reslizumab in the 400 cells/µL or greater subgroup (rate ratio, 0.55 [95% CI, 0.36-0.85]; P = .007). Asthma control was significantly improved with mepolizumab versus benralizumab (all subgroups: P < .05) and versus reslizumab in the 400 cells/µL or greater subgroup (P = .004). Benralizumab significantly improved lung function versus reslizumab in the 400 cells/µL or greater subgroup (P = .025). CONCLUSIONS: This ITC of the licensed doses suggests that mepolizumab was associated with significantly greater improvements in clinically significant exacerbations and asthma control compared with reslizumab or benralizumab in patients with similar blood eosinophil counts.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Asma/tratamento farmacológico , Interleucina-5/antagonistas & inibidores , Anticorpos Monoclonais Humanizados/efeitos adversos , Asma/imunologia , Asma/patologia , Eosinófilos/imunologia , Eosinófilos/patologia , Feminino , Humanos , Interleucina-5/imunologia , Contagem de Leucócitos , Masculino , Índice de Gravidade de Doença
13.
Am J Respir Crit Care Med ; 199(4): 508-517, 2019 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-30192638

RESUMO

RATIONALE: Eosinophils drive pathophysiology in stable and exacerbating eosinophilic asthma, and therefore treatment is focused on the reduction of eosinophil numbers. Mepolizumab, a humanized monoclonal antibody that neutralizes IL-5 and efficiently attenuates eosinophils, proved clinically effective in severe eosinophilic asthma but not in mild asthma. OBJECTIVES: To study the effect of mepolizumab on virus-induced immune responses in mild asthma. METHODS: Patients with mild asthma, steroid-naive and randomized for eosinophil numbers, received 750 mg mepolizumab intravenously in a placebo-controlled double-blind trial, 2 weeks after which patients were challenged with rhinovirus (RV) 16. FEV1, FVC, fractional exhaled nitric oxide, symptom scores (asthma control score), viral load (PCR), eosinophil numbers, humoral (luminex, ELISA), and cellular (flow cytometry) immune parameters in blood, BAL fluid, and sputum, before and after mepolizumab and RV16, were assessed. MEASUREMENTS AND MAIN RESULTS: Mepolizumab attenuated baseline blood eosinophils and their activation, attenuated trendwise sputum eosinophils, and enhanced circulating natural killer cells. Mepolizumab did not affect FEV1, FVC, and fractional exhaled nitric oxide, neither at baseline nor after RV16. On RV16 challenge mepolizumab did not prevent eosinophil activation but did enhance local B lymphocytes and macrophages and reduce neutrophils and their activation. Mepolizumab also enhanced secretory IgA and reduced tryptase in BAL fluid. Finally, mepolizumab affected particularly RV16-induced macrophage inflammatory protein-3a, vascular endothelial growth factor-A, and IL-1RA production in BAL fluid. CONCLUSIONS: Mepolizumab failed to prevent activation of remaining eosinophils and changed RV16-induced immune responses in mild asthma. Although these latter effects likely are caused by attenuated eosinophil numbers, we cannot exclude a role for basophils. Clinical trial registered with www.clinicaltrials.gov (NCT 01520051).


Assuntos
Antiasmáticos/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Asma/tratamento farmacológico , Linfócitos B/imunologia , Macrófagos/imunologia , Neutrófilos/imunologia , Infecções por Picornaviridae/imunologia , Rhinovirus , Asma/virologia , Líquido da Lavagem Broncoalveolar/citologia , Método Duplo-Cego , Feminino , Volume Expiratório Forçado , Humanos , Interleucina-5/antagonistas & inibidores , Masculino , Infecções por Picornaviridae/complicações , Rhinovirus/imunologia , Capacidade Vital , Adulto Jovem
14.
Curr Opin Pulm Med ; 25(1): 51-58, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30461530

RESUMO

PURPOSE OF REVIEW: To discuss the current use of oral corticosteroids (OCS) as a chronic treatment in patients with severe asthma and as a rescue treatment for patients presenting with acute exacerbations. RECENT FINDINGS: Airways disease is responsible for the bulk of OCS use in the community and considerable OCS-associated morbidity. I speculate that the key mechanism leading to a beneficial effect in these situations is depletion of circulating eosinophils resulting in a reduced response to potentially inhaled corticosteroid unresponsive recruitment signals to the airway mucosa. This effect is shared by anti-IL-5 biological agents, which have emerged as highly effective OCS-sparing agents. Mitigation of the adverse effects of OCS might also result from a better appreciation of features associated with a response to OCS and targeted, biomarker-directed use. SUMMARY: Longer term, there are real prospects that chronic and acute OCS use in asthma will be replaced by biological agents targeting eosinophilic airway inflammation more specifically and safely.


Assuntos
Corticosteroides/uso terapêutico , Antiasmáticos/uso terapêutico , Asma/tratamento farmacológico , Mucosa Respiratória/imunologia , Exacerbação dos Sintomas , Administração por Inalação , Administração Oral , Corticosteroides/administração & dosagem , Corticosteroides/efeitos adversos , Antiasmáticos/administração & dosagem , Antiasmáticos/efeitos adversos , Produtos Biológicos/uso terapêutico , Eosinófilos , Humanos , Interleucina-5/antagonistas & inibidores , Mucosa Respiratória/efeitos dos fármacos
15.
Rev. méd. Minas Gerais ; 29: e-2024, 2019.
Artigo em Português | LILACS | ID: biblio-1048021

RESUMO

Este documento é uma revisão do protocolo de asma grave da SMPCT de 2015, que se fez necessária devido à atualização de avanços em pesquisas, principalmente em fenotipagem/genotipagem e terapêutica da asma grave, além de asma grave na pediatria. A maioria da publicações relata que 5% a 10% dos asmáticos podem apresentar asma grave. Porém, levantamento na Holanda encontrou uma prevalência menor, de 3,6% ou 10,4/10000 habitantes, que parece ser mais próximo da realidade. Este protocolo tem como população alvo os pacientes com asma grave, adultos e pediátricos, conforme definições de asma grave da"International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma" de 2014 e GINA 2018.1,3 Seus potenciais utilizadores são especialistas em doenças respiratórias que lidam com asma grave, e que devem ser os responsáveis pela aplicação do protocolo, e também clínicos gerais, pediatras, médicos de cuidados primários, enfermeiros, fisioterapeutas e outros profissionais da saúde. É aconselhável consulta com um especialista em asma nos seguintes casos: asma de difícil diagnóstico, suspeita de asma ocupacional, asma persistente não controlada com exacerbações frequentes, asma com risco de morte, eventos adversos significativos ou suspeita de subtipos de asma grave.4 Este documento não tem a intenção de instituir um tratamento padronizado, mas estabelecer bases racionais para decisões em pacientes com asma grave, pois as recomendações não conseguem abranger toda a complexidade do julgamento clínico em casos individuais. Os autores recomendam sua revisão e atualização no período máximo de 3 anos, ou, se necessário, em tempo menor.


Assuntos
Humanos , Criança , Adolescente , Adulto , Asma , Corticosteroides , Agonistas de Receptores Adrenérgicos beta 2 , Asma/diagnóstico , Asma/tratamento farmacológico , Asma/terapia , Interleucina-5/antagonistas & inibidores , Corticosteroides/administração & dosagem , Corticosteroides/agonistas , Compostos Químicos , Agonistas de Receptores Adrenérgicos beta 2/administração & dosagem
16.
Biomed Res Int ; 2018: 5698212, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30519580

RESUMO

The current developments of the new biological drugs targeting interleukin 5 (IL-5) and IL-5 receptor allowed to expand the treatment options for severe hypereosinophilic asthma. Clinicians will then be able to choose between antibodies targeting either circulating IL-5 or its receptor expressed on eosinophils and basophils. The available clinical trials consistently reported favorable results about the reduction of exacerbations rate, improvement in quality of life, and sparing of the systemic steroid use, with a favorable safety profile. Two of these new drugs are administered subcutaneously, mepolizumab every 4 weeks and benralizumab every 8 weeks, whereas reslizumab is given intravenously monthly on a weigh-based dose. In the future, the research actions will be involved in the identification of a single biomarker or multiple biomarkers for the optimal choice of biological agents to be properly prescribed.


Assuntos
Antiasmáticos/farmacologia , Antiasmáticos/uso terapêutico , Asma/tratamento farmacológico , Subunidade alfa de Receptor de Interleucina-5/antagonistas & inibidores , Interleucina-5/antagonistas & inibidores , Animais , Asma/metabolismo , Humanos , Qualidade de Vida
17.
Eur Respir J ; 52(5)2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30309978

RESUMO

Benralizumab is an interleukin-5 receptor α-directed cytolytic monoclonal antibody that directly depletes eosinophils. Its relative efficacy versus other IL-5-targeted treatments for patients with severe, uncontrolled asthma is not yet fully characterised.We performed a matching-adjusted indirect comparison (MAIC) of benralizumab versus mepolizumab and reslizumab. Trials were selected through systematic review and evaluation of trial methods. Benralizumab patient-level data were weighted to match treatment-effect-modifying patient characteristics of comparator trials before indirect efficacy comparisons.After matching adjustment, benralizumab and mepolizumab reduced exacerbations versus placebo by 52% and 49%, respectively (rate ratio [RR] 0.94, 95% CI 0.78-1.13; n=1524) and reduced the rate of exacerbations requiring hospitalisation/emergency department visit by 52% and 52%, respectively (RR 1.00, 95% CI 0.57-1.75; n=1524). Benralizumab and mepolizumab similarly improved pre-bronchodilator forced expiratory volume in 1 s at 32 weeks (difference 0.03 L, 95% CI -0.06-0.12; n=1443). Benralizumab and reslizumab patient populations were too dissimilar to generate a sufficient effective sample size to produce a reliable estimate for MAIC.MAIC is a robust way to indirectly compare treatment efficacies from trials with heterogeneous patient populations. When baseline patient characteristics were matched across asthma trials, benralizumab and mepolizumab yielded similar efficacy.


Assuntos
Antiasmáticos/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Asma/terapia , Interleucina-5/antagonistas & inibidores , Receptores de Interleucina-5/antagonistas & inibidores , Antiasmáticos/efeitos adversos , Anticorpos Monoclonais Humanizados/efeitos adversos , Pesquisa Comparativa da Efetividade , Progressão da Doença , Humanos , Injeções Subcutâneas , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
18.
Praxis (Bern 1994) ; 107(21): 1129-1135, 2018.
Artigo em Alemão | MEDLINE | ID: mdl-30326819

RESUMO

CME: Mepolizumab, an Additional Therapeutic Agent for Severe Asthma Abstract. The challenging therapy of severe uncontrollable bronchial asthma aims primarily at sufficient symptom control and the minimization of the exacerbation rate. If, despite extended drug therapy, symptom control is very difficult to achieve, biologics should preferably be used instead of corticosteroid therapy. The aim of this article is to point out these different asthma therapy pathways and to describe diagnostic criteria as well as practical experiences through application in patients.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Asma/tratamento farmacológico , Corticosteroides/uso terapêutico , Asma/classificação , Asma/diagnóstico , Eosinofilia/classificação , Eosinofilia/diagnóstico , Eosinofilia/tratamento farmacológico , Humanos , Interleucina-5/antagonistas & inibidores , Prognóstico , Avaliação de Sintomas
19.
Medwave ; 18(6): e7301, 2018 Oct 24.
Artigo em Espanhol, Inglês | MEDLINE | ID: mdl-30365483

RESUMO

INTRODUCTION: Chronic rhinosinusitis is the inflammation of sinonasal mucosa lasting longer than 12 weeks. Two clinical forms are distinguished: chronic rhinosinusitis with polyps and without polyps. Patients with chronic rhinosinusitis with polyps exhibit high levels of interleukin 5, which promotes differentiation and survival of eosinophils. So, minimizing their circulation has been proposed as a new treatment strategy. However, there is no clarity regarding its real effectiveness. METHODS: To answer this question we used Epistemonikos, the largest database of systematic reviews in health, which is maintained by screening multiple information sources, including MEDLINE, EMBASE, Cochrane, among others. We extracted data from the systematic reviews, reanalyzed data of primary studies, conducted a meta-analysis and generated a summary of findings table using the GRADE approach. RESULTS AND CONCLUSIONS: We identified three systematic reviews included three primary studies overall, all corresponding to randomized trials. We concluded inhibitors of interleukin 5 might decrease nasal polyps score. Although they might be associated with adverse effects, these would be infrequent and of low severity. However, the certainty of the evidence is low.


Assuntos
Interleucina-5/imunologia , Rinite/tratamento farmacológico , Sinusite/tratamento farmacológico , Doença Crônica , Bases de Dados Factuais , Humanos , Interleucina-5/antagonistas & inibidores , Pólipos Nasais/tratamento farmacológico , Pólipos Nasais/imunologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Rinite/imunologia , Sinusite/imunologia
20.
Int Immunopharmacol ; 64: 223-231, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30199847

RESUMO

INTRODUCTION: Anti-interleukin-5 therapy has been proposed as a novel and promising treatment option in asthma treatment. However, the optimum monoclonal antibodies for asthma treatment remain uncertain. METHODS: We searched the PubMed, EMBASE and Cochrane databases from their inceptions to June 2018 for randomized controlled trials that reported pulmonary function, adverse events, Asthma Quality of Life Questionnaire (AQLQ) scores, and asthmatic exacerbations resulting from anti-interleukin-5 therapy in asthma patients. Extracted data were analyzed by pairwise and network meta-analysis. RESULTS: Twenty-one randomized studies were identified for this analysis. By pairwise meta-analysis using a placebo as the reference, patients treated with monoclonal antibodies were associated with significantly improved forced expiratory volume (FEV1) values (standard mean difference [SMD], 0.18; 95% confidence interval [CI], 0.12-0.23; P < 0.001), lower rates of adverse events (risk ratio [RR], 0.93; 95% CI, 0.90-0.97; P < 0.001) and significant improvements in the AQLQ scores (SMD, 0.20; 95% CI, 0.13-0.26; P < 0.001). There were no significant differences in exacerbations risks (RR, 0.68; 95% CI, 0.11-4.14; P = 0.097). According to network meta-analysis, adverse events-related benefits were seen only with reslizumab, while AQLQ scores benefits, and pulmonary function benefits were still seen with all three monoclonal antibodies. The assessment of rank probabilities indicated that reslizumab presented the greatest likelihood of having benefits for pulmonary function, reducing adverse events and improving AQLQ scores when compared with the placebo, and mepolizumab presented the best benefits for reducing asthmatic exacerbations. CONCLUSIONS: Anti-interleukin-5 therapy appears to be a safe and effective treatment for asthma patients with respect to pulmonary lung function, adverse events and AQLQ scores, and do not increase asthmatic exacerbations. Our network meta-analysis in patients with asthma suggests that reducing adverse events benefits due to reslizumab, and pulmonary lung function benefits as well as good AQLQ scores are seen with respect to the three antibodies. Network meta-analysis indicates the probability that the best anti-interlukin-5 therapy for asthma patients might be reslizumab, but further trials are required to determine the most effective asthma treatment drug.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Asma/tratamento farmacológico , Teorema de Bayes , Interleucina-5/antagonistas & inibidores , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/uso terapêutico , Asma/fisiopatologia , Asma/psicologia , Humanos , Pulmão/fisiopatologia , Metanálise em Rede , Viés de Publicação , Qualidade de Vida
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