Positioning of Tezepelumab in Severe Asthma.

Asthma is one of the most common chronic diseases and is estimated to be severe in 3%-10% of affected patients. There is a need for additional biologic treatments that are highly efficacious across the spectrum of severe uncontrolled asthma. Currently available drugs inhibit 1 or 2 specific cytokines or IgE antibodies and thus only partially suppress the complex type 2 (T2) inflammatory cascade. Biologics targeting more upstream molecules in the pathophysiological pathway of asthma could treat asthma more effectively. Tezepelumab is a human monoclonal immunoglobulin G2λ antibody that targets the cytokine thymic stromal lymphopoietin (TSLP). It is the first marketed biologic against an epithelial cell-derived cytokine, preventing binding of TSLP to its receptor and reducing the immune stimuli that TSLP can trigger in different asthma endotypes. Tezepelumab reduces downstream biomarkers of inflammation, such as blood and airway eosinophils, FeNO, IgE, IL-5, and IL-13. Tezepelumab provides a clinical benefit in severe asthma, reducing the annualized asthma exacerbation rate in patients with either high or low levels of biomarkers of T2 inflammation, although the effect is greater among those with high levels. The drug has been shown to improve asthma control, quality of life, and lung function and reduce airway hyperresponsiveness. Therefore, tezepelumab can be used across the spectrum of patients with severe uncontrolled asthma, especially in T2-high patients. This review includes a positioning statement by the authors, all of whom are members of the SEAIC Asthma Committee.

Red flags for clinical suspicion of eosinophilic granulomatosis with polyangiitis (EGPA).

BACKGROUND: Eosinophilic granulomatosis with polyangiitis (EGPA), is a rare ANCA-associated systemic vasculitis. Its overlapping features with other vasculitic or eosinophilic diseases, and the wide and heterogeneous range of clinical manifestations, often result in a delay to diagnosis. OBJECTIVE: To identify red flags that raise a suspicion of EGPA to prompt diagnostic testing and to present an evidence-based clinical checklist tool for use in routine clinical practice. METHODS: Systematic literature review and expert consensus to identify a list of red flags based on clinical judgement. GRADE applied to generate a strength of recommendation for each red flag and to develop a checklist tool. RESULTS: 86 studies were included. 40 red flags were identified as relevant to raise a suspicion of EGPA and assessed by the experts as being clinically significant. Experts agreed that a diagnosis of EGPA should be considered in a patient aged ≥6 years with a blood eosinophil level >1000 cells/µL if untreated and >500 cells/µL if previously treated with any medication likely to have altered the blood eosinophil count. The presence of asthma and/or nasal polyposis should reinforce a suspicion of EGPA. Red flags of asthma, lung infiltrates, pericarditis, cardiomyopathy, polyneuropathy, biopsy with inflammatory eosinophilic infiltrates, palpable purpura, digital ischaemia and ANCA positivity, usually anti-myeloperoxidase, among others, were identified. CONCLUSION: The identification of a comprehensive set of red flags could be used to raise a suspicion of EGPA in patients with eosinophilia, providing clinicians with an evidence-based checklist tool that can be integrated into their practice.

Positioning of Tezepelumab in Severe Asthma / Posicionamento do Tezepelumabe na Asma Grave

Asthma is one of the most common chronic diseases and is estimated to be severe in 3%-10% of affected patients. There is a need for additional biologic treatments that are highly efficacious across the spectrum of severe uncontrolled asthma. Currently available drugs inhibit 1 or 2 specific cytokines or IgE antibodies and thus only partially suppress the complex type 2 (T2) inflammatory cascade. Biologics targeting more upstream molecules in the pathophysiological pathway of asthma could treat asthma more effectively. Tezepelumab is a human monoclonal immunoglobulin G2λ antibody that targets the cytokine thymic stromal lymphopoietin (TSLP). It is the first marketed biologic against an epithelial cell–derived cytokine, preventing binding of TSLP to its receptor and reducing the immune stimuli that TSLP can trigger in different asthma endotypes. Tezepelumab reduces downstream biomarkers of inflammation, such as blood and airway eosinophils, FeNO, IgE, IL-5, and IL-13. Tezepelumab provides a clinical benefit in severe asthma, reducing the annualized asthma exacerbation rate in patients with either high or low levels of biomarkers of T2 inflammation, although the effect is greater among those with high levels. The drug has been shown to improve asthma control, quality of life, and lung function and reduce airway hyperresponsiveness. Therefore, tezepelumab can be used across the spectrum of patients with severe uncontrolled asthma, especially in T2-high patients. This review includes a positioning statement by the authors, all of whom are members of the SEAIC Asthma Committee (AU)

A asma é uma das doenças crônicas mais comuns e estima-se que seja grave em 3% a 10% dos pacientes afetados. Há necessidade de tratamentos biológicos adicionais que sejam altamente eficazes em todo o espectro da asma grave não controlada. Os medicamentos atualmente disponíveis inibem 1 ou 2 citocinas específicas ou anticorpos IgE e, portanto, suprimem apenas parcialmente a cascata inflamatória complexa tipo 2 (T2). Os produtos biológicos que visam moléculas mais a montante na via fisiopatológica da asma poderiam tratar a asma de forma mais eficaz. Tezepelumab é um anticorpo monoclonal humano imunoglobulina G2λ que tem como alvo a citocina linfopoietina estromal tímica (TSLP). É o primeiro produto biológico comercializado contra uma citocina derivada de células epiteliais, impedindo a ligação da TSLP ao seu receptor e reduzindo os estímulos imunológicos que a TSLP pode desencadear em diferentes endótipos de asma. Tezepelumabe reduz biomarcadores de inflamação a jusante, como eosinófilos no sangue e nas vias aéreas, FeNO, IgE, IL-5 e IL-13. O tezepelumab proporciona um benefício clínico na asma grave, reduzindo a taxa anualizada de exacerbação da asma em pacientes com níveis elevados ou baixos de biomarcadores de inflamação T2, embora o efeito seja maior entre aqueles com níveis elevados. Foi demonstrado que o medicamento melhora o controle da asma, a qualidade de vida e a função pulmonar e reduz a hiperresponsividade das vias aéreas. Portanto, o tezepelumabe pode ser usado em todo o espectro de pacientes com asma grave não controlada, especialmente em pacientes com T2 elevado. Esta revisão inclui uma declaração de posicionamento dos autores, todos membros do Comitê de Asma da SEAIC (AU)

Mepolizumab for the treatment of eosinophilic granulomatosis with polyangiitis: our experience

No disponible

Successful treatment of chronic pulmonary aspergillosis with isavuconazole

No disponible