scholarly journals Dupilumab is effective in type 2‐high asthma patients receiving high‐dose inhaled corticosteroids at baseline

Allergy ◽  
2020 ◽  
Vol 76 (1) ◽  
pp. 269-280
Author(s):  
Arnaud Bourdin ◽  
Alberto A. Papi ◽  
Jonathan Corren ◽  
J. Christian Virchow ◽  
Megan S. Rice ◽  
...  
Keyword(s):  
Inhaled Corticosteroids ◽  
High Dose ◽  
Asthma Patients

Wirksamkeit und Sicherheit von Dupilumab bei ganzjähriger allergischer Rhinitis und gleichzeitigem Asthma

2019 ◽  
Vol 7 (1) ◽  
pp. 27-28
Author(s):  
Susanne Lau
Keyword(s):  
Allergic Rhinitis ◽  
Inhaled Corticosteroids ◽  
Persistent Asthma ◽  
High Dose ◽  
Specific Response ◽  
Pivotal Phase ◽  
Runny Nose ◽  
Asthma Patients ◽  
Long Acting ◽  
Snot 22

Background: Dupilumab, an anti-IL-4 receptor a mAb, inhibits IL-4/IL-13 signaling, key drivers of type 2/TH2 immune diseases (eg, atopic/allergic disease). In a pivotal, phase 2b study (NCT01854047), dupilumab reduced severe exacerbations, improved lung function and quality of life, and was generally well tolerated in patients with uncontrolled persistent asthma despite using medium-to-high-dose inhaled corticosteroids plus long-acting b2-agonists. Objective: To examine dupilumabʼs effect on the 22-item Sino-Nasal Outcome Test (SNOT-22) total score and its allergic rhinitis (AR)-associated items in asthma patients with comorbid perennial allergic rhinitis (PAR). Methods: A post hoc analysis reporting data from the phase 2b study for the 200 and 300 mg every 2 week (q2w) doses under investigation in phase 3 (NCT02414854) was carried out. PAR was defined at study entry as a specific response to typical perennial antigens (IgE >0.35 Ku/L). Results: Overall, 241 (61%) patients had PAR. In asthma patients with PAR, dupilumab 300 mg q2w versus placebo significantly improved SNOT-22 total score (least squares mean difference, 25.98; 95% CI, 210.45 to 21.51; P 5.009) and all 4 AR-associated symptoms evaluated (nasal blockage, 20.60; 95% CI, 20.96 to 20.25; runny nose, 20.67; 95% CI, 21.04 to 20.31; sneezing, 20.55; 95% CI, 20.89 to 20.21; postnasal discharge, 20.49; 95% CI, 20.83 to 20.16; all P < .01). Dupilumab 200 mg q2w demonstrated numerical, but not statistically significant, decreases in SNOT-22 total score (21.82; 95% CI, 26.46 to 2.83; P 5 .443 vs placebo) and in each ARassociated symptom. In patients without PAR, no differences were observed for these measures versus placebo. Conclusions: Dupilumab 300 mg q2w significantly improved AR-associated nasal symptoms in patients with uncontrolled persistent asthma and comorbid PAR.

Diagnosis and Management of Severe Asthma

2018 ◽  
Vol 39 (01) ◽  
pp. 091-099 ◽  
Author(s):  
Kian Fan Chung
Keyword(s):  
Severe Asthma ◽  
Inhaled Corticosteroids ◽  
Immunoglobulin E ◽  
High Dose ◽  
Blood Eosinophil ◽  
Exhaled Breath ◽  
Eosinophilic Asthma ◽  
Severe Eosinophilic Asthma ◽  
Asthma Patients ◽  
Long Acting

AbstractSevere therapy-resistant asthma has been defined as “asthma which requires treatment with high dose inhaled corticosteroids (ICSs) plus a second controller (and/or systemic corticosteroids) to prevent it from becoming ‘uncontrolled’ or which remains ‘uncontrolled’ despite this therapy”. Patients who usually present with ‘difficult-to-treat asthma’ should first be assessed to determine whether he/she has asthma with the exclusion of other diagnoses and if so, whether the asthma can be classified as severe therapy-resistant. This necessitates an assessment of adherence to medications, confounding factors, and comorbidities. Increasingly, management of severe therapy-resistant asthma will be helped by the determination of phenotypes to optimize responses to existing and new therapies. Severe asthma patients are usually on a combination of high dose ICS and long-acting β-agonist (LABA) and, in addition, are often on a maintenance dose of oral corticosteroids. Phenotyping can be informed by measuring blood eosinophil counts and the level of nitric oxide in exhaled breath, and the use of sputum granulocytic counts. Severe allergic asthma and severe eosinophilic asthma are two defined phenotypes for which there are efficacious targeted biologic therapies currently available, namely anti-immunoglobulin E (IgE) and anti-interleukin (IL)-5 antibodies, respectively. Further progress will be realized with the definition of noneosinophilic or non-T2 phenotypes. It will be important for patients with severe asthma to be ultimately investigated and managed in specialized severe asthma centers.

scholarly journals The Significance of Hypothiocyanite Production via the Pendrin/DUOX/Peroxidase Pathway in the Pathogenesis of Asthma

2017 ◽  
Vol 2017 ◽  
pp. 1-7 ◽  
Author(s):  
Kenji Izuhara ◽  
Shoichi Suzuki ◽  
Masahiro Ogawa ◽  
Satoshi Nunomura ◽  
Yasuhiro Nanri ◽  
...  
Keyword(s):  
Airway Inflammation ◽  
Inhaled Corticosteroids ◽  
Airway Epithelial Cells ◽  
Airway Epithelial ◽  
Apical Side ◽  
Asthma Patients ◽  
High Doses ◽  
Antithyroid Agents ◽  
Antiasthma Drugs

Inhaled corticosteroids (ICSs) are used as first-line drugs for asthma, and various novel antiasthma drugs targeting type 2 immune mediators are now under development. However, molecularly targeted drugs are expensive, creating an economic burden on patients. We and others previously found pendrin/SLC26A4 as a downstream molecule of IL-13, a signature type 2 cytokine critical for asthma, and showed its significance in the pathogenesis of asthma using model mice. However, the molecular mechanism of how pendrin causes airway inflammation remained elusive. We have recently demonstrated that hypothiocyanite (OSCN−) produced by the pendrin/DUOX/peroxidase pathway has the potential to cause airway inflammation. Pendrin transports thiocyanate (SCN−) into pulmonary lumens at the apical side. Peroxidases catalyze SCN− and H2O2 generated by DUOX into OSCN−. Low doses of OSCN− activate NF-κB in airway epithelial cells, whereas OSCN− in high doses causes necrosis of the cells, inducing the release of IL-33 and accelerating inflammation. OSCN− production is augmented in asthma model mice and possibly in some asthma patients. Heme peroxidase inhibitors, widely used as antithyroid agents, diminish asthma-like phenotypes in mice, indicating the significance of this pathway. These findings suggest the possibility of repositioning antithyroid agents as antiasthma drugs.

P066 DUPILUMAB EFFICACY IN PATIENTS WITH TYPE 2 ASTHMA WITH/WITHOUT ALLERGIC PHENOTYPE RECEIVING HIGH-DOSE INHALED CORTICOSTEROIDS

2021 ◽  
Vol 127 (5) ◽  
pp. S32-S33
Author(s):  
A. Bourdin ◽  
J. Virchow ◽  
A. Papi ◽  
N. Lugogo ◽  
D. Halpin ◽  
...  
Keyword(s):  
Inhaled Corticosteroids ◽  
High Dose

scholarly journals Overuse of Oral Corticosteroids, Underuse of Inhaled Corticosteroids, and Implications for Biologic Therapy in Asthma

Respiration ◽  
2021 ◽  
pp. 1-6
Author(s):  
Katrien Eger ◽  
Marijke Amelink ◽  
Simone Hashimoto ◽  
Pieter-Paul Hekking ◽  
Cristina Longo ◽  
...  
Keyword(s):  
Biologic Therapy ◽  
Inhaled Corticosteroids ◽  
Inhalation Technique ◽  
High Dose ◽  
Inhaler Technique ◽  
Biologic Treatment ◽  
Asthma Patients ◽  
Oral Corticosteroids ◽  
High Doses ◽  
Steroid Sparing

<b><i>Background:</i></b> Asthma patients using high cumulative doses of oral corticosteroids (OCSs) are at risk of serious adverse events and are increasingly being treated with steroid-sparing asthma biologics. However, it is unknown whether prescribing these expensive biologics is always justified. <b><i>Objectives:</i></b> This study aimed to (1) assess the prevalence of asthma patients using high cumulative doses of OCSs, (2) explore the role of suboptimal inhaler therapy, and (3) estimate the proportion of patients to whom asthma biologics might be prescribed unnecessarily. <b><i>Methods:</i></b> All adults (<i>n</i> = 5,002) with at least 1 prescription of high-dose inhaled corticosteroids (≥500–1,000 mcg/day fluticasone-equivalent) and/or OCSs (GINA step 4–5) in 2010 were selected from a pharmacy database including 500,500 Dutch inhabitants, and sent questionnaires. Of 2,312 patients who returned questionnaires, 929 had asthma. We calculated the annual cumulative OCS dose and prescription fillings and checked inhaler technique in a sample of 60 patients. Patients estimated to have good adherence and inhaler proficiency who still required high doses of OCSs (≥420 mg/year) were considered candidates for initiating biologic treatment. <b><i>Results:</i></b> 29.5% of asthma patients on GINA 4–5 therapy used high doses of OCSs, of which 78.1% were likely to have poor therapy adherence or inadequate inhaler technique. Only 21.9% were considered definitive candidates for biologic therapy. <b><i>Conclusion:</i></b> High OCS use in Dutch GINA 4–5 asthma patients was common. However, in 4 out of 5 patients adherence to inhaled corticosteroid therapy and/or inhalation technique was considered suboptimal. Since optimizing inhaler therapy may reduce the need for OCSs, this should be mandatory before prescribing expensive steroid-sparing drugs.

scholarly journals Inhaled corticosteroids and the risk of type 2 diabetes among Swedish COPD patients

2020 ◽  
Vol 30 (1) ◽  
Author(s):  
Björn Ställberg ◽  
Christer Janson ◽  
Karin Lisspers ◽  
Gunnar Johansson ◽  
Florian S. Gutzwiller ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Incidence Rate ◽  
Inhaled Corticosteroids ◽  
High Dose ◽  
Primary Care Settings ◽  
Copd Patients ◽  
Increased Risk ◽  
Yearly Incidence ◽  
Using Data

Abstract This study reports the association of ICS use and the risk of type 2 diabetes mellitus (T2DM) in Swedish patients with COPD using data from real-world, primary care settings. A total of 7078 patients with COPD were included in this analysis and the 5-year cumulative incidence rate per 100,000 person years was 1506.9. The yearly incidence rate per 100,000 person years ranged from 850 to 1919. Use of ICS especially at a high dose in patients with COPD was related to an increased risk of T2DM.

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