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.

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.

scholarly journals Adherence to corticosteroids and clinical outcomes in mepolizumab therapy for severe asthma

2020 ◽  
Vol 55 (5) ◽  
pp. 1902259 ◽  
Author(s):  
Gráinne d'Ancona ◽  
Joanne Kavanagh ◽  
Cris Roxas ◽  
Linda Green ◽  
Mariana Fernandes ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Biologic Therapy ◽  
Inhaled Corticosteroids ◽  
Final Analysis ◽  
Good Adherence ◽  
Eosinophilic Asthma ◽  
Exacerbation Rate ◽  
Asthmatic Patients ◽  
Severe Eosinophilic Asthma ◽  
Asthma Patients

IntroductionInhaled corticosteroids (ICS) achieve disease control in the majority of asthmatic patients, although adherence to prescribed ICS is often poor. Patients with severe eosinophilic asthma may require treatment with oral corticosteroids (OCS) and/or biologic agents such as mepolizumab. It is unknown if ICS adherence changes on, or alters clinical response to, biologic therapy.MethodsWe examined ICS adherence and clinical outcomes in OCS-dependent severe eosinophilic asthma patients who completed 1 year of mepolizumab therapy. The ICS medicines possession ratio (MPR) was calculated (the number of doses of ICS issued on prescription/expected number) for the year before and the year after biologic initiation. Good adherence was defined as MPR >0.75, intermediate 0.74–0.51 and poor <0.5. We examined outcomes after 12 months of biologic therapy, including OCS reduction and annualised exacerbation rate (AER), stratified by adherence to ICS on mepolizumab.ResultsOut of 109 patients commencing mepolizumab, 91 who had completed 12 months of treatment were included in the final analysis. While receiving mepolizumab, 68% had good ICS adherence, with 16 (18%) having poor ICS adherence. ICS use within the cohort remained similar before (MPR 0.81±0.32) and during mepolizumab treatment (0.82±0.32; p=0.78). Patients with good adherence had greater reductions in OCS dose (median (interquartile range) OCS reduction 100 (74–100)% versus 60 (27–100)%; p=0.031) and exacerbations (AER change −2.1±3.1 versus 0.3±2.5; p=0.011) than those with poor adherence. Good ICS adherence predicted the likelihood of stopping maintenance OCS (adjusted OR 3.19, 95% CI 1.02–9.94; p=0.045).ConclusionICS nonadherence is common in severe eosinophilic asthma patients receiving mepolizumab, and is associated with a lesser reduction in OCS requirements and AER.

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 Management of the patient with eosinophilic asthma: a new era begins

2015 ◽  
Vol 1 (1) ◽  
pp. 00024-2015 ◽  
Author(s):  
Jantina C. de Groot ◽  
Anneke ten Brinke ◽  
Elisabeth H.D. Bel
Keyword(s):  
Inhaled Corticosteroids ◽  
Late Onset ◽  
Airflow Obstruction ◽  
Poor Quality ◽  
Eosinophilic Asthma ◽  
New Era ◽  
Systemic Corticosteroids ◽  
Asthma Patients ◽  
Oral Corticosteroids ◽  
Bronchial Biopsies

Now that it is generally accepted that asthma is a heterogeneous condition, phenotyping of asthma patients has become a mandatory part of the diagnostic workup of all patients who do not respond satisfactorily to standard therapy with inhaled corticosteroids. Late-onset eosinophilic asthma is currently one of the most well-defined asthma phenotypes and seems to have a different underlying pathobiology to classical childhood-onset, allergic asthma. Patients with this phenotype can be identified in the clinic by typical symptoms (few allergies and dyspnoea on exertion), typical lung function abnormalities (“fixed” airflow obstruction, reduced forced vital capacity and increased residual volume), typical comorbidities (nasal polyposis) and a good response to systemic corticosteroids. The definitive diagnosis is based on evidence of eosinophilia in bronchial biopsies or induced sputum, which can be estimated with reasonable accuracy by eosinophilia in peripheral blood. Until recently, patients with eosinophilic asthma had a very poor quality of life and many suffered from frequent severe exacerbations or were dependent on oral corticosteroids. Now, for the first time, novel biologicals targeting the eosinophil have become available that have been shown to be able to provide full control of this type of refractory asthma, and to become a safe and efficacious substitute for oral corticosteroids.

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

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.

scholarly journals Integrating high dose inhaled corticosteroids into oral corticosteroids stewardship

2020 ◽  
Vol 55 (1) ◽  
pp. 1902193 ◽  
Author(s):  
Arnaud Bourdin ◽  
Carey Suehs ◽  
Jérémy Charriot
Keyword(s):  
Inhaled Corticosteroids ◽  
High Dose ◽  
Oral Corticosteroids

scholarly journals Tracheobronchitis in ulcerative colitis: a case report of therapeutic response with infliximab and review of the literature

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Lisa Horgan ◽  
Siobhain Mulrennan ◽  
Lloyd D’Orsogna ◽  
Andrew McLean-Tooke
Keyword(s):  
Ulcerative Colitis ◽  
Case Report ◽  
Inhaled Corticosteroids ◽  
Rare Complication ◽  
High Dose ◽  
Clinical Effects ◽  
Case Presentation ◽  
First Case ◽  
Oral Corticosteroids ◽  
Symptomatic Remission

Abstract Background The extra-intestinal manifestation of tracheobronchitis is a rare complication of ulcerative colitis (UC). Here, we present a case of UC-related tracheobronchitis wherein the positive clinical effects of infliximab are demonstrated. Case presentation We report the case of a 39-year old woman who presented with a chronic productive cough on a distant background of surgically managed ulcerative colitis (UC). Our patient failed to achieve a satisfactory clinical improvement despite treatment with high dose inhaled corticosteroids, oral corticosteroids and azathioprine. Infliximab therapy was commenced and was demonstrated to achieve macroscopic and symptomatic remission of disease. Conclusions We present the first case report documenting the benefits of infliximab in UC-related tracheobronchitis.

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