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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:PurposeThe oral corticosteroid (OCS)-sparing effect of several biologics (BIOs) has been shown in clinical trials. To date, no study has evaluated differences in OCS dose reduction between BIO-initiated and BIO-non-initiated patients in real-world clinical practice. We compared dose reductions in maintenance OCS between BIO-initiated and BIO-non-initiated severe asthma patients in a real-world setting.Patients and methodsThis retrospective cohort study used the data from the Diagnosis Procedure Combination database of Medical Data Vision in Japan. Severe asthma patients with continuous use of OCS were selected from December 2015 to February 2020. The primary endpoint was the proportion reduction in daily maintenance OCS dose from Week 0 to Week 24. Analyses were performed using inverse probability treatment weighting.ResultsIn total, 2927 patients were included (BIO-initiated: 239 patients, BIO-non-initiated: 2688 patients). Adjusted median (quartile [Q] 1-Q3) proportion reduction in daily maintenance OCS dose at Week 24 from the index date was 25.0% (0.0-100.0%) and 0.0% (0.0-83.3%) in the BIO-initiated and BIO-non-initiated groups, respectively (Hodges-Lehmann estimate [95% confidence interval], 0.0000% [0.0000-0.3365%]). Respective proportions of patients in the BIO-initiated and BIO-non-initiated groups achieving dose reductions from the index date in the daily maintenance OCS dose at Week 24 were >0% reduction, 56.6% and 44.1% (odds ratio [OR] 1.6554); ≥25% reduction, 50.5% and 40.6% (OR 1.4888); ≥50% reduction, 42.8% and 33.7% (OR 1.4714); and 100% reduction, 26.2% and 24.4% (OR 1.1005).ConclusionAmong severe asthma patients, the daily dose of maintenance OCS was reduced with BIO treatment. Although a higher percentage of patients in the BIO-initiated group had an OCS reduction of ≤75% than the BIO-non-initiated group, we found no clear difference in OCS reduction. Our findings will be justified by further research that incorporates a longer observation period and variables excluded from this study.Trial registrationClinicalTrials.gov (NCT05136547).

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:Oral corticosteroids (OCS) are often prescribed to patients with asthma that remains uncontrolled with maintenance therapy. We performed a real-world analysis to describe the geographic distributions of patients with asthma and OCS dispensed in Nordic countries. This observational, retrospective study examined patient-level data from nationally prescribed drug registries from January to December 2018 for individuals aged ≥12 years in Denmark, Finland, and Sweden. Using an algorithm based on asthma treatment combinations defined by the Global Initiative for Asthma (GINA), we identified patients with asthma, those on GINA Step 4-5 treatments, and those being dispensed ≥2 courses of OCS and determined volumes of OCS dispensed to these patients over the 1-year analysis period. Data were plotted geographically within each country using colour-coded heat maps. The overall asthma prevalence rates were 7.4% in Denmark, 11.6% in Finland, and 8.1% in Sweden. In Denmark, Finland, and Sweden, respectively, the frequencies of patients on GINA Step 4-5 treatments were 19%, 15%, and 16%; among whom 10%, 23%, and 5% received ≥2 courses of OCS. The rates of patients on GINA Step 4-5 treatments who were dispensed OCS in each country were 23%, 30%, and 46%, of which 22%, 17%, and 10% were dispensed doses averaging ≥5 mg/day over the year. Heat maps revealed considerable heterogeneity in geographic densities of patients with asthma and OCS claims within each country. Taken together, these results demonstrate regional variations in estimated asthma severity, control, and OCS dispensed within and between countries. Patterns of medication use suggest that a high proportion of patients in Denmark, Finland, and Sweden are on GINA Step 4-5 treatments, many of whom are dispensed OCS; this poses a considerable corticosteroid burden to these patients. Geographic differences in medication use within and between Nordic countries may reflect variations in population characteristics and/or treatment approaches.

Project description:IntroductionAsthma is a heterogeneous disease with poorly defined phenotypes. Patients with severe asthma often receive multiple treatments including oral corticosteroids (OCS). Treatment may modify the observed metabotype, rendering it challenging to investigate underlying disease mechanisms. Here, we aimed to identify dysregulated metabolic processes in relation to asthma severity and medication.MethodsBaseline urine was collected prospectively from healthy participants (n=100), patients with mild-to-moderate asthma (n=87) and patients with severe asthma (n=418) in the cross-sectional U-BIOPRED cohort; 12-18-month longitudinal samples were collected from patients with severe asthma (n=305). Metabolomics data were acquired using high-resolution mass spectrometry and analysed using univariate and multivariate methods.ResultsA total of 90 metabolites were identified, with 40 significantly altered (p<0.05, false discovery rate <0.05) in severe asthma and 23 by OCS use. Multivariate modelling showed that observed metabotypes in healthy participants and patients with mild-to-moderate asthma differed significantly from those in patients with severe asthma (p=2.6×10-20), OCS-treated asthmatic patients differed significantly from non-treated patients (p=9.5×10-4), and longitudinal metabotypes demonstrated temporal stability. Carnitine levels evidenced the strongest OCS-independent decrease in severe asthma. Reduced carnitine levels were associated with mitochondrial dysfunction via decreases in pathway enrichment scores of fatty acid metabolism and reduced expression of the carnitine transporter SLC22A5 in sputum and bronchial brushings.ConclusionsThis is the first large-scale study to delineate disease- and OCS-associated metabolic differences in asthma. The widespread associations with different therapies upon the observed metabotypes demonstrate the need to evaluate potential modulating effects on a treatment- and metabolite-specific basis. Altered carnitine metabolism is a potentially actionable therapeutic target that is independent of OCS treatment, highlighting the role of mitochondrial dysfunction in severe asthma.

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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