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Rational oral corticosteroid use in adult severe asthma: A narrative review.

ABSTRACT: OCS play an important role in the management of asthma. However, steroid-related AE are common and represent a leading cause of morbidity. Limited published studies suggest OCS usage varies across countries and recent registry data indicate that at least 25-60% of patients with severe asthma in developed countries may at some stage be prescribed OCS. Recent evidence indicate that many patients do not receive optimal therapy for asthma and are often prescribed maintenance OCS or repeated steroid bursts to treat exacerbations. Given the recent progress in adult severe asthma and new treatment options, judicious appraisal of steroid use is merited. A number of strategies and add-on therapies are now available to treat severe asthma. These include increasing specialist referral for multidisciplinary assessments and implementing OCS-sparing interventions, such as improving guideline adherence and add-on tiotropium and macrolides. Biologics have recently become available for severe asthma; these agents reduce asthma exacerbations and lower OCS exposure. Further research, collaboration and consensus are necessary to develop a structured stewardship approach including realistic OCS-weaning programmes for patients with severe asthma on regular OCS; education and public health campaigns to improve timely access to specialized severe asthma services for treatment optimization; and implementing targeted strategies to identify patients who warrant OCS use using objective biomarker-based strategies.

SUBMITTER: Chung LP

PROVIDER: S-EPMC7027745 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Rational oral corticosteroid use in adult severe asthma: A narrative review.

Chung Li Ping LP Upham John W JW Bardin Philip G PG Hew Mark M

Respirology (Carlton, Vic.) 20191112 2

OCS play an important role in the management of asthma. However, steroid-related AE are common and represent a leading cause of morbidity. Limited published studies suggest OCS usage varies across countries and recent registry data indicate that at least 25-60% of patients with severe asthma in developed countries may at some stage be prescribed OCS. Recent evidence indicate that many patients do not receive optimal therapy for asthma and are often prescribed maintenance OCS or repeated steroid ...[more]

PMID: 31713955

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Project description:BACKGROUND:Oral corticosteroid (OCS) treatment for severe asthma is associated with substantial disease burden. Thus, OCS dosage reduction is desirable. Relative efficacy of biologics in reducing OCS treatment for severe, uncontrolled asthma is not fully characterized. OBJECTIVE:We performed a matching-adjusted indirect comparison (MAIC) to assess the relative effects on OCS treatment reduction of three biologic asthma treatments. METHODS:In MAIC of benralizumab vs. mepolizumab and vs. dupilumab, patient-level data from the Phase III benralizumab OCS-sparing trial, ZONDA, were weighted to match treatment effect-modifying patient characteristics in comparator trials. RESULTS:After matching adjustment, mean difference between benralizumab and mepolizumab for OCS reduction was 6.08% (95% CI -22.22-34.38; P = .67) by week 24, and odds ratio of OCS elimination was 2.32 (95% CI 0.48-11.15; P = .29). A trend in annual asthma exacerbation rate reduction favouring benralizumab over mepolizumab was observed, although it was not statistically significant (rate ratio [RR] = 0.56 [95% CI 0.28-1.13; P = .11]). Mean difference between benralizumab and dupilumab for OCS reduction was -0.71% (95% CI -20.56-19.15; P = .94), and odds ratio of OCS elimination was 2.26 (95% CI 0.52-9.84; P = .28). A non-significant trend in annual asthma exacerbation rate reduction favouring benralizumab over dupilumab was observed (RR = 0.50 [95% CI 0.20-1.28; P = .15]). Effective sample size was 49% (72 vs. 148) and 25% (36 vs. 142) of original sample size for MAIC of benralizumab vs. mepolizumab and benralizumab vs. dupilumab, respectively. CONCLUSIONS AND CLINICAL RELEVANCE:Following patient baseline characteristics matching across clinical trials, benralizumab demonstrated efficacy comparable to mepolizumab and dupilumab for OCS dosage reduction, OCS elimination, and annual exacerbation rate reduction. Comparatively low effective sample sizes indicated substantial differences for patient populations between ZONDA and mepolizumab and dupilumab trials.

Project description:BACKGROUND: Corticosteroid insensitivity is a major barrier of treatment for some chronic inflammatory diseases, such as severe asthma, but the molecular mechanism of the insensitivity has not been fully elucidated. The object of this study is to investigate the role of protein phosphate 2A (PP2A), a serine/threonine phosphatase, on corticosteroid sensitivity in severe asthma. METHODOLOGY/PRINCIPAL FINDINGS: Corticosteroid sensitivity was determined by the dexamethasone ability to inhibit TNF?-induced IL-8 or LPS-induced TNF? production. PP2A expression, glucocorticoid receptor (GR) nuclear translocation defined as the nuclear/cytoplasmic GR ratio and phosphorylation of GR-Ser²²?, c-Jun N-terminal kinase 1 (JNK1) and PP2A were analysed by Western-blotting. Phosphatase activity was measured by fluorescence-based assay. Okadaic acid (OA), a PP2A inhibitor, reduced corticosteroid sensitivity with reduced GR nuclear translocation and increased GR phosphorylation in U937 monocytic cells. PP2A knockdown by RNA interference showed similar effects. IL-2/IL-4 treatment to U937 reduced corticosteroid sensitivity, and PP2A expression/activity. In peripheral blood mononuclear cells (PBMCs) from severe asthma, the PP2A expression and activity were significantly reduced with concomitant enhancement of PP2A(C)-Tyr³?? phosphorylation compared with those in healthy volunteers. As the results, GR-Ser²²? and JNK1 phosphorylation were increased. The expression and activity of PP2A were negatively correlated with phosphorylation levels of GR-Ser²²?. Furthermore, co-immunoprecipitation assay in U937 cells revealed that PP2A associated with GR and JNK1 and IL-2/IL-4 exposure caused dissociation of each molecule. Lastly, PP2A overexpression increased corticosteroid sensitivity in U937 cells. CONCLUSIONS/SIGNIFICANCE: PP2A regulates GR nuclear translocation and corticosteroid sensitivity possibly by dephosphorylation of GR-Ser²²? via dephosphorylation of upstream JNK1. This novel mechanism will provide new insight for the development of new therapy for severe asthma.

Project description:OBJECTIVE:To summarize the current literature on non-steroidal anti-inflammatory drug and corticosteroid use during the coronavirus disease 2019 (COVID-19) pandemic, recognizing that these are commonly used treatments in the field of headache medicine. BACKGROUND:The use of non-steroidal anti-inflammatory drugs and corticosteroids in patients during the COVID-19 pandemic has been a controversial topic within the medical community and international and national health organizations. Lay press and social media outlets have circulated opinions on this topic despite the fact that the evidence for or against the use of these medications is sparse. In the field of headache medicine, these medications are used commonly and both patients and clinicians may have questions or hesitations pertaining to their use during the COVID-19 pandemic. METHODS:A detailed search of the scientific and popular literature was performed. RESULTS:There is limited literature pertaining to the safety of non-steroidal anti-inflammatory drugs and corticosteroids during the COVID-19 pandemic. To date, there are no clear scientific data that preclude the use of non-steroidal anti-inflammatory drugs in the general population who may acquire COVID-19 or in those acutely infected with the virus. Several health organizations have concluded that treatment with corticosteroids during active infection should be avoided due to concerns of prolonged viral shedding in the respiratory tract and the lack of survival benefit based on the data from past coronaviruses and influenza virus; specific exceptions exist including treatment for underlying asthma or chronic obstructive pulmonary disease, septic shock, and acute respiratory distress syndrome. CONCLUSION:Scientific information regarding the COVID-19 pandemic is constantly evolving, and limited or contradictory information can lead to confusion for both patients and clinicians. It is recommended that prior to prescribing non-steroidal anti-inflammatory drugs and steroids for the treatment of headache, clinicians have open discussions with their patients about the potential risks and benefits of using these medications during the COVID-19 pandemic. This manuscript summarizes the currently available evidence and understanding about these risks and benefits to help clinicians navigate such discussions.

Dataset Information

Rational oral corticosteroid use in adult severe asthma: A narrative review.

Publications

Rational oral corticosteroid use in adult severe asthma: A narrative review.

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