One More Time: The Impact of Inhaled Corticosteroid Withdrawal on IMPACT.
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ABSTRACT:
SUBMITTER: Han MK
PROVIDER: S-EPMC7605195 | biostudies-literature | 2020 Nov
REPOSITORIES: biostudies-literature
Publications
One More Time: The Impact of Inhaled Corticosteroid Withdrawal on IMPACT.
Han MeiLan K MK Lipson David A DA Singh Dave D Martinez Fernando J FJ
American journal of respiratory and critical care medicine 20201101 9
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| S-EPMC7605197 | biostudies-literature
Project description:Rationale: In the IMPACT (Informing the Pathway of Chronic Obstructive Pulmonary Disease Treatment) trial, fluticasone furoate (FF)/umeclidinium (UMEC)/vilanterol (VI) significantly reduced exacerbations compared with FF/VI or UMEC/VI in patients with symptomatic chronic obstructive pulmonary disease and a history of exacerbations.Objectives: To understand whether inhaled corticosteroid (ICS) withdrawal affected IMPACT results, given direct transition from prior maintenance medication to study medication at randomization.Methods: Exacerbations and change from baseline in trough FEV1 and St. George's Respiratory Questionnaire results were analyzed by prior ICS use. Exacerbations were also analyzed while excluding data from the first 30 days.Measurements and Main Results: FF/UMEC/VI significantly reduced the annual moderate/severe exacerbation rate compared with UMEC/VI in prior ICS users (29% reduction; P < 0.001), but only a numerical reduction was seen among prior ICS nonusers (12% reduction; P = 0.115). To minimize impact from ICS withdrawal, in an analysis excluding the first 30 days, FF/UMEC/VI continued to significantly reduce the annual on-treatment moderate/severe exacerbation rate (19%; P < 0.001) compared with UMEC/VI. The benefit of FF/UMEC/VI compared with UMEC/VI was seen for severe exacerbation rates, regardless of prior ICS use (prior ICS users, 35% reduction; P < 0.001; non-ICS users, 35% reduction; P = 0.018), and overall when excluding the first 30 days (29%; P < 0.001). Improvements from baseline with FF/UMEC/VI compared with UMEC/VI were also maintained throughout the study for both trough FEV1 and St. George's Respiratory Questionnaire, regardless of prior ICS use.Conclusions: These data support the important treatment effects of FF/UMEC/VI combination therapy on exacerbation reduction, lung function, and quality of life that do not appear to be related to abrupt ICS withdrawal.Clinical trial registered with www.clinicaltrials.gov (NCT02164513).
| S-EPMC7605201 | biostudies-literature
Project description:The therapeutic value of inhaled corticosteroids (ICSs) for COPD is limited. In published RCTs, ICS could be withdrawn in COPD patients without increasing exacerbation risk when bronchodilator treatment is optimized. Here we report on the feasibility and risks of ICS withdrawal in Dutch general practice for COPD patients without an indication for ICSs. In our pragmatic trial, general practitioners decided autonomously which of their COPD patients on ICS treatment could stop this, how this was done, and whether additional bronchodilator therapy was needed. We recruited 62 COPD patients (58 analysed) who were eligible for ICS withdrawal in 79 practices. In 32 patients (55.2%, 95% CI: 42.5-67.3%) ICS was withdrawn successfully, 19 (32.8%, 95% CI: 22.1-45.6%) restarted ICS treatment within six months, 12 patients (20.7%, 95% CI: 12.3-32.8%) had a moderate exacerbation, and one patient had a severe exacerbation. ICS withdrawal was successful in just over half of the patients with COPD without an indication for ICS.
| S-EPMC7547069 | biostudies-literature
Project description:PurposeIn the Withdrawal of Inhaled Steroids during Optimized Bronchodilator Management (WISDOM) trial, inhaled corticosteroid (ICS) withdrawal in patients with chronic obstructive pulmonary disease receiving triple therapy (long-acting β2-agonist+long-acting muscarinic antagonist+ICS) did not change moderate/severe exacerbation risk. However, many patients were not taking triple therapy before study participation. This analysis was conducted to eliminate the impact of non-ICS users on WISDOM results by re-analyzing the data using only the subset of patients who were taking triple therapy at screening.Patients and methodsThe effect of ICS withdrawal on moderate/severe exacerbation risk in the subgroup of WISDOM patients taking triple therapy before enrolling in the study was evaluated in this post hoc analysis. Additionally, the effect of ICS withdrawal in patients with a history of ≥2 exacerbations in the previous year and various blood eosinophil counts was assessed.ResultsOverall, 39.0% (n=970: ICS continuation, 479; ICS withdrawal, 491) of the WISDOM trial population were taking triple therapy at screening. Baseline characteristics were generally similar between groups. Moderate/severe exacerbation risk between the ICS withdrawal and continuation groups (hazard ratio [HR], 1.05; 95% confidence interval [CI]: 0.89-1.25) was not increased in patients taking triple therapy at screening versus the overall trial population (HR [95% CI]: 1.06 [0.94-1.19]). However, in patients with a history of ≥2 exacerbations, exacerbation risk (HR [95% CI]) increased nominally with blood eosinophil count from 1.07 [0.81-1.41] (≥100 cells/μL) to 1.45 [0.58-3.60] (≥400 cells/μL).ConclusionConsistent with results from the overall WISDOM trial population, ICS withdrawal did not increase exacerbation risk in patients taking triple therapy at screening. Patients with a history of frequent exacerbations and higher blood eosinophil counts could benefit from continuation of ICS-based therapy.
| S-EPMC7667507 | biostudies-literature
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| S-EPMC10798772 | biostudies-literature
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| S-EPMC8095067 | biostudies-literature
Project description:BackgroundAn increase in serious adverse events with both regular formoterol and regular salmeterol in chronic asthma has been demonstrated in comparison with placebo in previous Cochrane reviews. This increase was significant in trials that did not randomise participants to an inhaled corticosteroid, but less certain in the smaller numbers of participants in trials that included an inhaled corticosteroid in the randomised treatment regimen.ObjectivesWe set out to compare the risks of mortality and non-fatal serious adverse events in trials which have randomised patients with chronic asthma to regular formoterol versus regular salmeterol, when each are used with an inhaled corticosteroid as part of the randomised treatment.Search strategyTrials were identified using the Cochrane Airways Group Specialised Register of trials. Manufacturers' web sites of clinical trial registers were checked for unpublished trial data and Food and Drug Administration (FDA) submissions in relation to formoterol and salmeterol were also checked. The date of the most recent search was July 2009.Selection criteriaControlled clinical trials with a parallel design, recruiting patients of any age and severity of asthma were included if they randomised patients to treatment with regular formoterol versus regular salmeterol (each with a randomised inhaled corticosteroid), and were of at least 12 weeks duration.Data collection and analysisTwo authors independently selected trials for inclusion in the review and extracted outcome data. Unpublished data on mortality and serious adverse events were sought from the sponsors and authors.Main resultsEight studies met the eligibility criteria of the review recruiting 6,163 adults and adolescents. There were seven studies (involving 5,935 adults and adolescents) comparing formoterol and budesonide to salmeterol and fluticasone. All but one study administered the products as a combined inhaler, and most used formoterol 50 mcg and budesonide 400 mcg twice daily versus salmeterol 50 mcg and fluticasone 250 mcg twice daily. There were two deaths overall (one on each combination) and neither were thought to be related to asthma.There was no significant difference between treatment groups for non-fatal serious adverse events, either all-cause (Peto OR 1.14; 95% CI 0.82 to 1.59, I(2) = 26%) or asthma-related (Peto OR 0.69; 95% CI 0.37 to 1.26, I(2) = 33%). Over 23 weeks the rates for all-cause serious adverse events were 2.6% on formoterol and budesonide and 2.3% on salmeterol and fluticasone, and for asthma-related serious adverse events, 0.6% and 0.8% respectively.There was one study (228 adults) comparing formoterol and beclomethasone to salmeterol and fluticasone, but there were no deaths or hospital admissions.No studies were found in children.Authors' conclusionsThe seven identified studies in adults did not show any significant difference in safety between formoterol and budesonide in comparison with salmeterol and fluticasone. Asthma-related serious adverse events were rare, and there were no reported asthma-related deaths. There was a single small study comparing formoterol and beclomethasone to salmeterol and fluticasone in adults, but no serious adverse events occurred in this study. No studies were found in children.Overall there is insufficient evidence to decide whether regular formoterol and budesonide or beclomethasone have equivalent or different safety profiles from salmeterol and fluticasone.
| S-EPMC4015852 | biostudies-literature
Project description:BackgroundRecent evidence has established a beneficial effect of systemic corticosteroids for treatment of moderate-to-severe COVID-19.ObjectiveTo determine if inhaled corticosteroid use is associated with COVID-19 outcomes.MethodsIn a nationwide cohort of hospitalized SARS-CoV-2 test-positive individuals in Denmark, we estimated the 30-day hazard ratio of intensive care unit (ICU) admission or death among users of inhaled corticosteroids (ICS) compared with users of bronchodilators (β2 -agonist/muscarinic-antagonists), and non-users of ICS overall, with Cox regression adjusted for age, sex, and other confounders. We repeated these analyses among influenza test-positive patients during 2010-2018.ResultsAmong 6267 hospitalized SARS-CoV-2 patients, 614 (9.8%) were admitted to ICU and 677 (10.8%) died within 30 days. ICS use was associated with a hazard ratio of 1.09 (95% CI [CI], 0.67 to 1.79) for ICU admission and 0.78 (95% CI, 0.56 to 1.11) for death compared with bronchodilator use. Compared with no ICS use overall, the hazard ratio of ICU admission or death was 1.17 (95% CI, 0.87-1.59) and 1.02 (95% CI, 0.78-1.32), respectively. Among 10 279 hospitalized influenza patients, of which 951 (9.2%) were admitted to ICU and 1275 (12.4%) died, the hazard ratios were 1.43 (95% CI, 0.89-2.30) and 1.11 (95% CI, 0.85-1.46) for ICU admission, and 0.80 (95% CI, 0.63-1.01) and 1.03 (95% CI, 0.87-1.22) for death compared with bronchodilator use and no ICS use overall, respectively.ConclusionOur results do not support an effect of inhaled corticosteroid use on COVID-19 outcomes, however we can only rule out moderate-to-large reduced or increased risks.Study registrationThe study was pre-registered at encepp.eu (EUPAS35897).
| S-EPMC8441753 | biostudies-literature
Project description:BackgroundAdrenal suppression is a side effect of long-term use of inhaled corticosteroids (ICS). Hair cortisol concentration (HCC) measurement is a noninvasive tool for measuring adrenal function that may be useful for asthmatic patients who are on long-term ICS treatment. The aim of this study was to compare HCC between children with and without asthma and to explore the association between HCC and ICS dose in asthmatic children.MethodsA cross-sectional observational study in subjects with or without asthma (n = 72 and 226, respectively, age 6-21 years). Hair samples were obtained from the posterior vertex for each subject and data on medication use were collected using questionnaires. HCC was analyzed by liquid chromatography-mass spectrometry in the most proximal 3 cm of hair.ResultsMedian HCC was significantly lower in subjects with asthma than in subjects without asthma: 1.83 pg/mg and 2.39 pg/mg, respectively (P value after adjustment for age, sex, and body mass index: .036). Median HCC was 1.98 pg/mg in asthmatics using no ICS, 1.84 pg/mg in those using a low dose, 1.75 pg/mg in those on a medium dose, and 1.46 in those using a high ICS dose (P = .54).ConclusionWe observed a significantly lower HCC in asthmatics than in healthy controls and a nonsignificant trend of lower HCC with increasing ICS dose. Whether HCC measurement may be used to detect individuals at risk for hypocortisolism and may be useful to monitor adrenal function in asthmatic children using ICS needs to be further investigated.
| S-EPMC7003950 | biostudies-literature
Project description: Not available
| S-EPMC6486274 | biostudies-literature