Oral Corticosteroids Tapering in Severe Asthma.
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ABSTRACT:
SUBMITTER: Boulet LP
PROVIDER: S-EPMC8017580 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundSevere asthma (SA) may require frequent courses or chronic use of oral corticosteroids (OCS), inducing many known side effects and complications. Therefore, it is important to identify risk factors of chronic use of OCS in SA, considering the heterogeneity of clinical and inflammatory asthma phenotypes. Another aim of the present analysis is to characterize a subpopulation of severe asthmatics, in whom blood eosinophil counts (BEC) remain elevated despite chronic OCS treatment.MethodsIn a cross-sectional analysis of 982 SA patients enrolled in the Belgian Severe Asthma Registry (BSAR) between March 2009 and February 2019, we investigated the characteristics of the OCS treated patients with special attention to their inflammatory profile.ResultsAt enrollment, 211 (21%) SA patients were taking maintenance OCS (median dose: 8 [IQR: 5-10]) mg prednisone equivalent). BEC was high (> 400/mm3) in 44% of the OCS treated population. Multivariable logistic regression analysis showed that risk factors for chronic use of OCS in SA were late-onset asthma (i.e. age of onset > 40 yr), frequent exacerbations (i.e. ≥2 exacerbations in the previous year) and non-atopic asthma. Late-onset asthma was also a predictor for persistently high BEC in OCS treated SA patients.ConclusionThese data showed a significant association between a persistently high BEC and late-onset asthma in OCS treated SA patients. Whether it is poor compliance to treatment or corticosteroid insensitivity the reasons for this association warrants further investigation.
| S-EPMC7424982 | biostudies-literature
Project description:BackgroundOral corticosteroids are important components of pharmacotherapy in severe asthma. Our objective was to describe the extent, trends, and factors associated with exposure to oral corticosteroids (OCS) in a severe asthma cohort.MethodsWe used administrative health databases of British Columbia, Canada (2000-2014) and validated algorithms to retrospectively create a cohort of severe asthma patients. Exposure to OCS within each year of follow-up was measured in two ways: maintenance use as receiving on average ≥ 2.5 mg/day (prednisone-equivalent) OCS, and episodic use as the number of distinct episodes of OCS exposure for up to 14 days. Trends and factors associated with exposure on three time axes (calendar year, age, and time since diagnosis) were evaluated using Poisson regression.Results21,144 patients (55.4% female; mean entry age 28.7) contributed 40,803 follow-up years, in 8.2% of which OCS was used as maintenance therapy. Maintenance OCS use declined by 3.8%/calendar year (p < 0.001). The average number of episodes of OCS use was 0.89/year, which increased by 1.1%/calendar year (p < 0.001). Trends remained significant for both exposure types in adjusted analyses. Both maintenance and episodic use increased by age and time since diagnosis.ConclusionsThis population-based study documented a secular downward trend in maintenance OCS use in a period before widespread use of biologics. This might have been responsible for a higher rate of exacerbations that required episodic OCS therapy. Such trends in OCS use might be due to changes in the epidemiology of severe asthma, or changes in patient and provider preferences over time.
| S-EPMC8034163 | biostudies-literature
Project description:Eosinophilic chronic rhinosinusitis (ECRS), which is a subgroup of chronic rhinosinusitis with nasal polyps, is characterized by eosinophilic airway inflammation extending across both the upper and lower airways. Some severe cases are refractory even after endoscopic sinus surgery, likely because of local steroid insensitivity. Although real-life studies indicate that treatment with omalizumab for severe allergic asthma improves the outcome of coexistent ECRS, the underlying mechanisms of omalizumab in eosinophilic airway inflammation have not been fully elucidated. Twenty-five patients with ECRS and severe asthma who were refractory to conventional treatments and who received omalizumab were evaluated. Nineteen of twenty-five patients were responsive to omalizumab according to physician-assessed global evaluation of treatment effectiveness. In the responders, the levels of peripheral blood eosinophils and fractionated exhaled nitric oxide (a marker of eosinophilic inflammation) and of CCL4 and soluble CD69 (markers of eosinophil activation) were reduced concomitantly with the restoration of corticosteroid sensitivity. Omalizumab restored the eosinophil-peroxidase-mediated PP2A inactivation and steroid insensitivity in BEAS-2B. In addition, the local inflammation simulant model using BEAS-2B cells incubated with diluted serum from each patient confirmed omalizumab's effects on restoration of corticosteroid sensitivity via PP2A activation; thus, omalizumab could be a promising therapeutic option for refractory eosinophilic airway inflammation with corticosteroid resistance.
| S-EPMC8301363 | biostudies-literature
Project description:Benralizumab is an interleukin-5 receptor ?-directed cytolytic monoclonal antibody approved in several countries for the add-on maintenance treatment of patients with severe eosinophilic asthma aged 12?years and older. In the 28-week Phase III ZONDA trial (ClinicalTrials.gov identifier: NCT02075255), benralizumab produced a median 75% reduction from baseline in oral corticosteroid (OCS) dosage (versus 25% for placebo) while maintaining asthma control for patients with OCS-dependent severe asthma. This manuscript presents the detailed protocol for the Phase IIIb PONENTE (ClinicalTrials.gov identifier: NCT03557307), a study that will build on the findings from ZONDA. As the largest steroid-sparing study undertaken in severe asthma, PONENTE has a faster steroid tapering schedule for prednisone dosages ?7.5?mg·day-1 than previous studies, and it includes an evaluation of adrenal insufficiency and an algorithm to taper OCS dosage when prednisone dosage is ?5?mg·day-1. It also has a longer maintenance phase to assess asthma control for up to 6 months after completion of OCS tapering. The two primary endpoints are whether patients achieve 100% reduction in daily OCS use and whether patients achieve 100% reduction in daily OCS or achieve OCS dosage ?5?mg·day-1, if adrenal insufficiency prevented further reduction, both sustained over ?4?weeks without worsening of asthma. Safety and change from baseline in health-related quality of life will also be assessed. PONENTE should provide valuable guidance for clinicians on tapering OCS dosage, including the management of adrenal insufficiency, following benralizumab initiation for the treatment of patients who are OCS-dependent with severe, uncontrolled eosinophilic asthma.
| S-EPMC6759576 | biostudies-literature
Project description:Dose-related efficacy and safety of fevipiprant (QAW039), an oral DP2 (CRTh2) receptor antagonist, was assessed in patients with allergic asthma uncontrolled by low-dose inhaled corticosteroids (ICS).Adult patients were randomised to 12?weeks' treatment with once-daily (1, 3, 10, 30, 50, 75, 150, 300 or 450?mg q.d) or twice-daily (2, 25, 75 or 150?mg b.i.d) fevipiprant (n=782), montelukast 10?mg q.d (n=139) or placebo (n=137). All patients received inhaled budesonide 200??g b.i.dFevipiprant produced a statistically significant improvement in the primary end-point of change in pre-dose forced expiratory volume in 1 s at week 12 (p=0.0035) with a maximum model-averaged difference to placebo of 0.112?L. The most favourable pairwise comparisons to placebo were for the fevipiprant 150?mg q.d and 75?mg b.i.d groups, with no clinically meaningful differences between q.d and b.i.d Montelukast also demonstrated a significant improvement in this end-point. No impact on other efficacy end-points was observed. Adverse events were generally mild/moderate in severity, and were evenly distributed across doses and treatments.Fevipiprant appears to be efficacious and well-tolerated in this patient population, with an optimum total daily dose of 150?mg. Further investigations into the clinical role of fevipiprant in suitably designed phase III clinical trials are warranted.
| S-EPMC5593367 | biostudies-other
Project description: Not available
| S-EPMC7328335 | biostudies-literature
Project description: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.
| S-EPMC7027745 | biostudies-literature
Project description:Airway microbiota in severe asthma and relationship to asthma clusters and severity
| PRJEB11495 | ENA
Project description:Purpose: Evaluated the transcriptional effects of an effective oral dosing of antental corticosteroids using betamethasone-phophate compared to the clinical treatment with the combination drug betamethasone-phosphate+betamethasone-acetate for fetal lung maturation. Methods: RNA-sequencing of the fetal hippocampus, liver and lung was done. Differential expression analysis was done using read counts. Results: There were no significant differences between oral Beta-P and the clinical treatment in the fetal hippocampus. Small differences were detected in the fetal lung associated with cellular proliferation and in the fetal liver. Conclusions: Oral betamethasone-phosphate is an effective oral treatment that does not cause toxic effect in the fetal brain despite the higher dose.
2019-09-25 | GSE131194 | GEO
Project description:BackgroundIn short-term studies, poor adherence to inhaled corticosteroids (ICS) has been associated with worse asthma control, but the association of long-term adherence and disease control remains unclear.ObjectiveTo assess the relationship between 12-year adherence to ICS and asthma control in patients with adult-onset asthma.MethodsAs part of the Seinäjoki Adult Asthma Study, 181 patients with clinically confirmed new-onset adult asthma and regular ICS medication were followed-up for 12 years. Adherence (%) to ICS was assessed individually ((µg dispensed/µg prescribed)×100) during the follow-up. Asthma control was evaluated after 12 years of treatment according to the Global Initiative for Asthma 2010 guideline.ResultsAsthma was controlled in 31% and not controlled (partly controlled or uncontrolled) in 69% of the patients. Patients with not-controlled asthma were more often male, older, nonatopic and used higher doses of ICS than those with controlled disease. The mean±sd 12-year adherence to ICS was 63±38% in patients with controlled asthma and 76±40% in patients with not-controlled disease (p=0.042). Among patients with not-controlled asthma, those with lower 12-year adherence (<80%) had more rapid decline in forced expiratory volume in 1 s (-47 mL·year-1) compared to patients with better adherence (≥80%) (-40 mL·year-1) (p=0.024). In contrast, this relationship was not seen in patients with controlled asthma.ConclusionsIn adult-onset asthma, patients with not-controlled disease showed better 12-year adherence to ICS treatment than those with controlled asthma. In not-controlled disease, adherence <80% was associated with more rapid lung function decline, underscoring the importance of early recognition of such patients in routine clinical practice.
| S-EPMC7869602 | biostudies-literature