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Severe asthma imposes a significant burden on patients, families and healthcare systems. Management is difficult, due to disease heterogeneity, co-morbidities, complexity in care pathways and differences between national or regional healthcare systems. Better understanding of the mechanisms has enabled a stratified approach to the management of severe asthma, supporting the use of targeted treatments with biologicals. However, there are still many issues that require further clarification. These include selection of a certain biological (as they all target overlapping disease phenotypes), the definition of response, strategies to enhance the responder rate, the duration of treatment and its regimen (in the clinic or home-based) and its cost-effectiveness. The EAACI Guidelines on the use of biologicals in severe asthma follow the GRADE approach in formulating recommendations for each biological and each outcome. In addition, a management algorithm for the use of biologicals in the clinic is proposed, together with future approaches and research priorities.
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Asma , Asma/diagnóstico , Asma/tratamento farmacológico , Asma/epidemiologia , Análise Custo-Benefício , Humanos , FenótipoRESUMO
Five biologicals have been approved for severe eosinophilic asthma, a well-recognized phenotype. Systematic reviews (SR) evaluated the efficacy and safety of benralizumab, dupilumab, mepolizumab, omalizumab and reslizumab (alphabetical order) compared to standard of care for severe eosinophilic asthma. PubMed, Embase and Cochrane Library were searched to identify RCTs and health economic evaluations, published in English. Critical and important asthma-related outcomes were evaluated for each of the biologicals. The risk of bias and the certainty of the evidence were assessed using GRADE. 19 RCTs (three RCTs for benralizumab, three RCTs for dupilumab, three RCTs for mepolizumab, five RCTs for omalizumab and five RCTs for reslizumab), including subjects 12 to 75 years old (except for omalizumab including also subjects 6-11 years old), ranging from 12 to 56 weeks were evaluated. All biologicals reduce exacerbation rates with high certainty of evidence: benralizumab incidence rate ratio (IRR) 0.53 (95% CI 0.39 to 0.72), dupilumab (IRR) 0.43 (95% CI 0.32 to 0.59), mepolizumab IRR 0.49 (95% CI 0.38 to 0.66), omalizumab (IRR) 0.56 (95% CI 0.40 to 0.77) and reslizumab (IRR) 0.46 (95% CI 0.37 to 0.58). Benralizumab, dupilumab and mepolizumab reduce the daily dose of oral corticosteroids (OCS) with high certainty of evidence. All evaluated biologicals probably improve asthma control, QoL and FEV1 , without reaching the minimal important difference (moderate certainty). Benralizumab, mepolizumab and reslizumab slightly increase drug-related adverse events (AE) and drug-related serious AE (low to very low certainty of evidence). The incremental cost-effectiveness ratio per quality-adjusted life year value is above the willingness to pay threshold for all biologicals (moderate certainty). Potential savings are driven by decrease in hospitalizations, emergency and primary care visits. There is high certainty that all approved biologicals reduce the rate of severe asthma exacerbations and for benralizumab, dupilumab and mepolizumab for reducing OCS. There is moderate certainty for improving asthma control, QoL, FEV1 . More data on long-term safety are needed together with more efficacy data in the paediatric population.
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Antiasmáticos , Asma , Produtos Biológicos , Adolescente , Adulto , Idoso , Antiasmáticos/uso terapêutico , Anticorpos Monoclonais Humanizados , Asma/tratamento farmacológico , Produtos Biológicos/efeitos adversos , Criança , Humanos , Pessoa de Meia-Idade , Omalizumab/uso terapêutico , Qualidade de Vida , Adulto JovemRESUMO
INTRODUCTION: Atopic dermatitis (AD) is a chronic, inflammatory skin disease characterized by itchy, painful, and dry skin. Despite the great number of available therapies, economic evaluations are still needed to provide evidence on their cost efficiency. This research aimed to evaluate the cost effectiveness of the Janus kinase (JAK) inhibitor abrocitinib (200 mg) compared with dupilumab (300 mg), tralokinumab (300 mg), baricitinib (2 and 4 mg), and upadacitinib (15 and 30 mg) for the treatment of patients with severe AD from the Spanish National Health System (NHS) perspective. METHODS: A hybrid model consisting of a decision tree linked to a Markov model was developed to estimate costs, quality-adjusted life-years (QALYs), total years in response and incremental cost-per-QALY gained (willingness-to-pay [WTP] threshold: 25,000/QALY). Adults with severe AD entered the decision tree and response (75% reduction in baseline Eczema Area and Severity Index score, EASI-75) was considered at 16 and 52 weeks. After this time, patients entered the Markov model (remainder of the 10-year time horizon), which consisted of three health states: maintenance with active therapy, subsequent treatment, or death. All costs were presented in 2022 euros (). Additionally, cost per number-needed-to-treat (NNT) was calculated for abrocitinib and dupilumab based on a head-to-head post-hoc analysis. RESULTS: Abrocitinib 200 mg was dominant (i.e., lower incremental costs and higher incremental benefit) compared with all studied alternatives (dupilumab 300 mg, tralokinumab 300 mg, baricitinib 2 and 4 mg, upadacitinib 15 and 30 mg) with a QALYs gain of 0.49, 0.60, 0.64, 0.43, 0.45, and 0.08, respectively, and per-person costs savings of 22,097, 24,140, 14,825, 7,116, 12,805, and 45,189, respectively. Considering the WTP threshold, abrocitinib was dominant or cost effective compared with all alternatives for most simulations. Additionally, abrocitinib was dominant compared with all alternatives when evaluating the cost effectiveness over a 5-year time horizon. NNT showed that abrocitinib was dominant versus dupilumab. CONCLUSIONS: The results of the study show that abrocitinib is a cost-effective therapy compared with other JAK inhibitors and biological therapies from the Spanish NHS perspective.
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BACKGROUND: Although cross-reactivity with other plant-based foods and latex has been described, allergies to potatoes and tomatoes are uncommon. OBJECTIVE: To study the different sensitization patterns in patients who are allergic to potatoes and/or tomatoes. METHODS: Skin prick tests were carried out with fresh foods and extracts, specific IgE determination and allergen detection by SDS-PAGE and IgE-Immunoblotting with both raw and heated potato and tomato extracts. RESULTS: In 10 patients, two thermostable allergens to potato extract were detected; the first one with a molecular weight that is compatible with Sola t 1 (43 kDa, patatin) and the second one with a molecular weight of 14-22 kDa, which could correspond to the allergens Sola t 4 (16 kDa) and Sola t 2 and Sola t 3 (21 kDa); in two patients who are allergic to potatoes and two patients who are allergic to tomatoes, a thermostable allergen that is compatible to Sola I 2 (50 kDa) was detected. The patient had presented oral allergy syndrome with some types of potatoes and showed higher IgE reactivity to two thermostable potato allergens. CONCLUSIONS: The allergen sensitization patterns were similar in all the patients that had been studied, regardless of the symptoms. A new allergen involved in the allergy to solanaceae plants has been detected.
Antecedentes: Aunque se ha descrito reactividad cruzada con alimentos vegetales y látex, la alergia a la papa y al tomate es infrecuente. Objetivo: Estudiar los diferentes patrones de sensibilización en pacientes alérgicos a la patata o tomate. Métodos: Se realizaron pruebas de punción cutánea con extractos y alimentos frescos, determinación de IgE específica y detección de alérgenos mediante SDS-PAGE e IgE-Immunoblotting con extractos de patata y tomate crudos y calientes. Resultados: En 10 pacientes se detectaron alérgenos termoestables a extracto de patata, uno de peso molecular compatible con Sola t 1 (43 kDa, patatina) y otro de 14-22 kDa que podría corresponder a los alérgenos Sola t 4 (16 kDa), Sola t 2 y Sola t 3 (21 kDa); en dos pacientes alérgicos a la patata y dos alérgicos al tomate se detectó un alérgeno termoestable de aproximadamente 42 kDa. En un paciente alérgico al tomate se detectó un alérgeno termoestable compatible con Sola l 2 (50 kDa); había presentado síndrome de alergia oral con algunos tipos de patatas y mostró mayor reactividad IgE a dos alérgenos termoestables de la patata. Conclusiones: Los patrones de sensibilización a los alérgenos fueron similares en los pacientes, independientemente de los síntomas. Se ha detectado un nuevo alérgeno implicado en la alergia a las solanáceas.
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Hipersensibilidade Alimentar/imunologia , Solanum lycopersicum/efeitos adversos , Solanum tuberosum/efeitos adversos , Adolescente , Adulto , Alérgenos/análise , Feminino , Hipersensibilidade Alimentar/diagnóstico , Humanos , Solanum lycopersicum/química , Solanum lycopersicum/imunologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Testes Cutâneos , Solanum tuberosum/química , Solanum tuberosum/imunologia , Adulto JovemRESUMO
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