Withdrawal Of Inhaled Corticosteroids Research Articles

Based on what parameters is safe to discontinuate inhaled corticosteroids in children with asthma?

Objective Remission of childhood asthma has not been widely studied. Patients in clinical remission continue to have some degree of bronchial hyperresponsiveness (BHR). The aim of this study was to investigate whether clinical parameters and lung function test are good parameters for discontinuation of inhaled corticosteroids (ICS) in asthmatic children, including patients with persistent BHR, as measured by the methacholine challenge test (MCT). Methods One year after discontinuation of inhaled corticosteroids (ICS), MCT was performed in a group of 40 asthmatic children to confirm or exclude BHR. In all patients, ICS treatment was discontinued based on the same parameters: symptoms, spirometry, daily PEF, and negative bronchodilator test. After achieving complete asthma control for at least 6 to 12 months, ICS treatment was stepped down and discontinued. Clinical course and spirometry were followed up after ICS discontinuation. Results Positive MCT was found in 50% of the patients. There was no statistically significant difference between the positive and negative MCT groups in age at initiation and discontinuation of ICS therapy, duration of ICS therapy, duration of stepping down period, FEV1, and PEF at the time of withdrawal of ICS and one year later. ICS treatment had to be restarted in two patients from the positive MCT group, due to recurrence of asthma symptoms. Conclusion Clinical parameters, normal spirometry, daily PEF values, and a negative bronchodilator test are good parameters for discontinuing ICS treatment in asthmatic children, even in patients with persistent BHR. Children should continue to be monitored, as symptoms may recur.

Investigating the rationale for COPD maintenance therapy prescription across Europe, findings from a multi-country study

This study aims to understand healthcare professionals’ thoughts and motivations about optimal management and treatment of patients with chronic obstructive pulmonary disease (COPD). We conducted a DELPHI survey through an online questionnaire distributed to 220 panellists from six European countries and a discrete choice experiment to describe the relationship between selected clinical criteria and the initial COPD treatment of choice. One hundred twenty-seven panellists (general practitioners [GPs] and pulmonologists) completed the survey. Despite the familiarity and use (89.8%) of the GOLD classification for initial treatment selection, a frequent use of LAMA/LABA/ICS was noted. In fact, panellists agreed that inhaled corticosteroids (ICS) are over-prescribed in the primary care setting. Our study showed that GPs felt less confident than pulmonologists with ICS withdrawal. This mismatch observed between best practice and behaviour indicates the need to increase awareness and efforts to improve the adherence to guidelines in clinical practice.

Impact of triple therapy on mortality in COPD.

Only a few therapies have been shown to prolong survival in specific patients with COPD. In recent years, the IMPACT and the ETHOS trials suggested that triple therapy (a combination of inhaled corticosteroid (ICS), long-acting muscarinic antagonist (LAMA) and long-acting β2-agonist (LABA) given in a single inhaler) may reduce mortality compared with dual bronchodilation. These results need however to be interpreted with caution. These trials were not powered by design to evaluate the impact of triple therapy on mortality as mortality was a secondary outcome. In addition, mortality reduction has to be put in perspective with the low mortality rate in both studies (<2%). Furthermore, a key methodological issue is that up to 70-80% of patients had ICS withdrawal at the enrolment in the LABA/LAMA arms, but none in the ICS-containing treatment arms. It is possible that ICS withdrawal may have contributed to some early death events. Finally, the inclusion and exclusion criteria of both trials were designed to select patients likely to respond to ICS. There are no conclusive data yet that triple therapy reduces mortality in COPD. Future, well-designed and -powered trials are needed to validate the findings on mortality.

A Prediction Scoring Model for the Effect of Withdrawal or Addition of Inhaled Corticosteroids in Patients with Chronic Obstructive Pulmonary Disease.

The aims of this study were to develop a scoring model that predicts the effects of withdrawing inhaled corticosteroids (ICSs) from triple therapy and to examine its adaptability when applied to assess the effect of adding ICSs to dual bronchodilators patients with chronic obstructive pulmonary disease (COPD). A scoring model was developed using the IMPACT study dataset, consisting of 2389 COPD patients treated with triple therapy before enrollment (ICS withdrawal dataset). The developed model consisted of COPD duration, Acute exacerbation history, Sex, Pulmonary function tests, blood Eosinophil count, and Race (CASPER) and was used to predict composite events of moderate-to-severe exacerbation, all-cause mortality, and pneumonia. Treatment heterogeneity was assessed using Cox interaction analyses. The CASPER model was applied to 540 COPD patients treated with dual bronchodilator before enrollment (ICS addition dataset). Validity was assessed using Harrell's C-index, time-dependent receiver operating characteristic curves, and calibration plots. The cumulative incidence of the composite event was 60.1% over 12 months in the ICS withdrawal dataset. Cox interaction analyses revealed that ICS was different according to race and blood eosinophil counts. The hazard ratios (HRs) for dual bronchodilator compared with triple therapy were 1.318 (95% confidence interval (CI)=1.170-1.485; P-value <0.001) in whites and 0.922 (95% CI = 0.712-1.195; P-value=0.541) in other races. The treatment effect was different in the eosinophil count ≥0.3 group (HR = 1.586; 95% CI = 1.274-1.975) and in the eosinophil count = 0.1-0.3 group (HR = 1.211; 95% CI = 1.041-1.408), but it was same in the eosinophil count <0.1 (HR = 1.009; P-value=0.940). The CASPER model performed well with good discrimination and calibration, which were superior to the prediction based on exacerbation history and blood eosinophil count. The presented CASPER model might be able to predict and compare the risk of composite events when dual bronchodilator or triple therapy is administered to COPD patients.

Clinical and Economic Impact of Long-Term Inhaled Corticosteroid Withdrawal in Patients with Chronic Obstructive Pulmonary Disease Treated with Triple Therapy in Spain.

PurposeTo determine the clinical and economic impact of inhaled corticosteroid (ICS) withdrawal in Spanish patients with COPD receiving triple therapy (TT) with ICS, long-acting β2-agonist (LABA), and long-acting muscarinic antagonist (LAMA).Patients and MethodsThis was an observational, retrospective study of BIG-PAC database medical records. Patients aged ≥40 years receiving TT from 2016 to 2018 were followed for 1 year. Two cohorts were identified: patients continuing TT (ICS+LABA+LAMA), and patients receiving TT with ICS withdrawn (LABA+LAMA). Variables included medication, exacerbations (moderate and severe), pneumonia, mortality, health resource use (HRU), and cost per patient/year. Cohorts were compared using propensity score matching (PSM). Multivariate statistical analysis using analysis of covariance and Cox proportional risks was conducted.ResultsOf 6541 patients included, 5740 (87.8%) continued TT and 801 (12.2%) had ICS withdrawn. Patients with ICS withdrawal were younger, had lower disease burden, higher ICS doses, and more exacerbations compared with those continuing ICS. PSM matched 795 patients in each cohort. Mean age was 68.5 years (SD: 11.2), 69.9% were male, and mean Charlson index was 2.0. Patients with ICS withdrawal had more total exacerbations in the 12 months following withdrawal compared with patients continuing TT (36.6% vs 31.4%; p=0.030). No significant differences were found for pneumonia (3.3% vs 3.6%; p=0.583) and mortality (9.9% vs 7.5%; p=0.092). Median time to first exacerbation was shorter in patients with ICS withdrawal compared with those continuing ICS (HR: 0.69, 95% CI: 0.57–0.83; p<0.001). Mean health cost per patient/year among patients with ICS withdrawal was higher than those continuing TT (€2993 vs €2130; p<0.001).ConclusionICS withdrawal in patients with COPD receiving TT was associated with increased exacerbations, HRU, and costs compared with continuing TT, with health and economic impacts on patients and the Spanish National Healthcare System, respectively. Pneumonia and mortality rates were similar between groups.

Single-Inhaler Triple versus Dual Bronchodilator Therapy in COPD: Real-World Comparative Effectiveness and Safety.

PurposeRandomized trials report that single-inhaler triple therapy is more effective than dual bronchodilators at reducing exacerbations in patients with chronic obstructive pulmonary disease (COPD). However, this effect may have been influenced by the forced withdrawal of inhaled corticosteroids (ICS) at randomization. We used an adaptive selection new-user design to compare single-inhaler triple therapy with dual bronchodilators in real-world clinical practice.Patients and MethodsWe identified a cohort of COPD patients, 40 years or older, treated during 2017–2020, from the United Kingdom’s Clinical Practice Research Datalink, a real-world practice setting. ICS-naïve patients initiating single-inhaler triple therapy or dual bronchodilators were compared on the incidence of COPD exacerbation and pneumonia over one year, after adjustment by propensity score weighting.ResultsThe cohort included 4106 new users of single-inhaler triple therapy and 29,702 of dual bronchodilators. Single-inhaler triple therapy was the first maintenance treatment in 44% of the users and 43% had no COPD exacerbations in the prior year. The adjusted hazard ratio (HR) of a first moderate or severe exacerbation with triple therapy relative to dual bronchodilators was 1.08 (95% confidence interval (CI): 1.00–1.16). Among patients with two or more prior exacerbations the HR was 0.83 (95% CI: 0.74–0.92), while for those with prior asthma diagnosis it was 0.86 (95% CI: 0.70–1.06) and with blood eosinophil count >300 cells/µL it was 0.89 (95% CI: 0.76–1.05). The incidence of severe pneumonia was increased with triple therapy (HR 1.50; 95% CI: 1.29–1.75).ConclusionIn a real-world setting of COPD treatment among ICS-naïve patients, thus unaffected by ICS withdrawal, single-inhaler triple therapy was not more effective than dual bronchodilators at reducing the incidence of exacerbation, except among patients with multiple exacerbations. Single-inhaler triple therapy should be initiated mainly in patients with multiple exacerbations while, for most others, dual bronchodilators are just as effective whilst avoiding the excess risk of severe pneumonias.

A descriptive cohort study of withdrawal from inhaled corticosteroids in COPD patients

Inhaled corticosteroid (ICS) therapy is widely prescribed without a history of exacerbations and consensus guidelines suggest withdrawal of ICS in these patients would reduce the risk of side effects and promote cost-effective prescribing. The study describes the prescribing behaviour in the United Kingdom (UK) in relation to ICS withdrawal and identifies clinical outcomes following withdrawal using primary and secondary care electronic health records between January 2012 and December 2017. Patients with a history ≥12 months’ exposure who withdrew ICS for ≥6 months were identified into two cohorts; those prescribed a long-acting bronchodilator maintenance therapy and those that were not prescribed any maintenance therapy. The duration of withdrawal, predictors of restarting ICS, and clinical outcomes were compared between both patient cohorts. Among 76,808 patients that had ≥1 prescription of ICS in the study period, 11,093 patients (14%) withdrew ICS therapy at least once during the study period. The median time without ICS was 9 months (IQR 7–14), with the majority (71%) receiving subsequent ICS prescriptions after withdrawal. Patients receiving maintenance therapy with a COPD review at withdrawal were 28% less likely to restart ICS (HR: 0.72, 95% CI 0.61, 0.85). Overall, 69% and 89% of patients that withdrew ICS had no recorded exacerbation event or COPD hospitalisation, respectively, during the withdrawal. This study provides evidence that most patients withdrawing from ICS do not experience COPD exacerbations and withdrawal success can be achieved by carefully planning routine COPD reviews whilst optimising the use of available maintenance therapies.

Pulmonologists' Opinion on the Use of Inhaled Corticosteroids in Chronic Obstructive Pulmonary Disease Patients in Spain: A Cross-Sectional Survey.

IntroductionIdentifying the variables that guide decision-making in relation to the use of inhaled corticosteroids (ICS) can contribute to the appropriate use of these drugs. The objective of this study was to identify the clinical variables that physicians consider most relevant for prescribing or withdrawing ICS in COPD.MethodsA cross-sectional survey was conducted in Spain from November 2020 to May 2021. Therapeutic decisions on the use of ICS in 11 hypothetical COPD patient profiles were collected using an online survey answered by specialists with experience in the management of patients with COPD. Mixed-effects logistic regression was used to analyze the impact of patients’ characteristics in the therapeutic decision for prescribing ICS or proceeding to its withdrawal.ResultsA total of 74 pulmonologists agreed to collaborate in the survey and answered the questionnaire. The results showed great variability, with only 2 profiles achieving consensus for starting or withdrawing the treatment. The frequency and severity of exacerbations influenced the decision to prescribe ICS in a dose-response fashion (1 exacerbation odds ratio (OR) = 1.86, 95% confidence interval (CI) 1.02 to 3.43, two exacerbations OR = 11.6, 95% CI: 4.47 to 30.2 and three OR = 123, 95% CI: 25 to 601). Similarly, increasing blood eosinophils and history of asthma were associated with ICS use. On the other hand, pneumonia reduced the probability of initiating treatment with ICS (OR = 0.54 [0.29 to 0.98]). Lung function and dyspnea degree did not influence the clinician’s therapeutic decision. The results for withdrawal of ICS were similar but in the opposite direction.ConclusionIn accordance with guidelines, exacerbations, blood eosinophils and history of asthma or pneumonia are the factors considered by pulmonologist for the indication or withdrawal of ICS. However, the agreement in prescription or withdrawal of ICS when confronted with hypothetical cases is very low, suggesting a great variability in clinical practice.

Inhaled Corticosteroid Withdrawal and Change in Lung Function in Primary Care Patients with Chronic Obstructive Pulmonary Disease in England.

Rationale: In chronic obstructive pulmonary disease (COPD), inhaled corticosteroids (ICS) are associated with pneumonia, highlighting the importance of investigating subgroups of patients who may benefit from prolonged ICS use. Despite this, the WISDOM (Withdrawal of Inhaled Steroids during Optimized Bronchodilator Management) trial found a greater decline in forced expiratory volume in 1 second (FEV1) in patients with COPD who withdrew from ICS compared with patients who remained on triple therapy. Objectives: We investigated the association between ICS withdrawal and the rate of FEV1 decline in patients with COPD using routinely collected electronic healthcare records. Methods: Using CPRD (Clinical Practice Research Datalink) Aurum and Hospital episode statistics, we included patients with COPD who had been on triple therapy for at least 4 months. Patients were categorized into those who withdrew from ICS and those who remained on triple therapy during follow-up. Three cohorts were created: 1) patients meeting the WISDOM trial eligibility criteria; 2) patients with COPD not restricted by the WISDOM trial eligibility criteria; and 3) patients who would have been excluded from the WISDOM trial on the basis of their comorbidities. Mixed linear regression was used to model the association between ICS withdrawal and the rate of FEV1 decline (ml/year) adjusted for baseline characteristics. Results: A total of 6,008 patients with COPD met the WISDOM eligibility criteria, of which 9.0% withdrew from ICS. Mean rates of FEV1 declined -7.8 ml/year (95% confidence interval [CI], -19.7 to 4.1) for withdrawers and -15.2 ml/year (95% CI, -18.7 to -11.8) for those who remained on triple therapy (difference, P = 0.264). A total of 60,645 patients with COPD were not restricted by the WISDOM eligibility criteria. The mean rate of FEV1 decline was -32.6 ml/year (95% CI, -33.6 to -31.5) for withdrawers and -36.4 ml/year (95% CI, -39.4 to -33.4) for those who remained on triple therapy. A total of 32,882 patients with COPD were included in the last population representing those who would have been excluded from the WISDOM trial because of their comorbidities. The mean rate of FEV1 decline was -29.4 ml/year (95% CI, -30 to -28.1) in withdrawers and -31.3 ml/year (95% CI, -35 to -27.5) in those who remained on triple therapy. Conclusions: The rate of FEV1 decline was similar between patients on triple therapy and patients who withdrew from ICS regardless of the specific COPD population studied. In routine clinical practice, few patients with COPD meet WISDOM eligibility criteria, and few patients are withdrawn from ICS.

STOP: an open label crossover trial to study ICS withdrawal in patients with a combination of obesity and low-inflammatory asthma and evaluate its effect on asthma control and quality of life

BackgroundAsthma patients with obesity often have a high disease burden, despite the use of high-dose inhaled corticosteroids (ICS). In contrast to asthmatics with normal weight, the efficacy of ICS in patients with obesity and asthma is often relatively low. Meanwhile, patients do suffer from side effects, such as weight gain, development of diabetes, cataract, or high blood pressure. The relatively poor response to ICS might be explained by the low prevalence of type 2 inflammatory patterns (T2-low) in patients with asthma and obesity. T2-low inflammation is characterized by low eosinophilic count, low Fractional exhaled NO (FeNO), no clinically allergy-driven asthma, and no need for maintenance oral corticosteroids (OCS). We aim to study whether ICS can be safely withdrawn in patients with T2-low asthma and obesity while maintaining an equal level of asthma control. Secondary outcomes focus on the prevalence of ‘false-negative’ T2-low phenotypes (i.e. T2-hidden) and the effect of ICS withdrawal on parameters of the metabolic syndrome. This study will lead to a better understanding of this poorly understood subgroup and might find new treatable traits.MethodsThe STOP trial is an investigator-initiated, multicenter, non-inferiority, open-label, crossover study aiming to assess whether ICS can be safely withdrawn in adults aged 17–75 years with T2-low asthma and obesity (body mass index (BMI) ≥ 30 kg/m2). Patients will be randomly divided into two arms (both n = 60). One arm will start with fixed-dose ICS (control group) and one arm will taper and subsequently stop ICS (intervention group). Patients in the intervention group will remain ICS naïve for ten weeks. After a washout of 4 weeks, patients will crossover to the other study arm. The crossover study takes 36 weeks to complete. Patients will be asked to participate in the extension study, to investigate the long-term metabolic benefits of ICS withdrawal.DiscussionThis study yields valuable data on ICS tapering in patients with T2-low asthma and obesity. It informs future guidelines and committees on corticosteroid-sparing algorithms in these patients.Trial registration Netherlands Trial Register, NL8759, registered 2020–07-06, https://www.trialregister.nl/trial/8759.Protocol version and date: version 2.1, 20 November 2020.

Pros and Cons of Inhaled Corticosteroids Withdrawal in Chronic Obstructive Pulmonary Disease

Pros and Cons of Inhaled Corticosteroids Withdrawal in Chronic Obstructive Pulmonary Disease

Triple Inhaler versus Dual Bronchodilator Therapy in COPD: Real-World Effectiveness on Mortality

Randomized trials of triple therapy including an inhaled corticosteroid (ICS) for chronic obstructive pulmonary disease (COPD) reported remarkable benefits on mortality compared with dual bronchodilators, likely resulting from ICS withdrawal at randomization. We compared triple therapy with dual bronchodilator combinations on major COPD outcomes in a real-world clinical practice setting. We identified a cohort of COPD patients, age 50 or older, treated during 2002-2018, from the United Kingdom’s Clinical Practice Research Datalink. Patients initiating treatment with a long-acting muscarinic antagonist (LAMA), a long-acting beta2-agonist (LABA) and an ICS on the same day, were compared with patients initiating a LAMA and LABA, weighted by fine stratification of propensity scores. Subjects were followed-up one year for all-cause mortality, severe exacerbation and pneumonia. The cohort included 117,729 new-users of LAMA-LABA-ICS and 26,666 of LAMA-LABA. The adjusted hazard ratio (HR) of all-cause mortality with LAMA-LABA-ICS compared with LAMA-LABA was 1.17 (95% CI: 1.04-1.31) while for severe exacerbation and pneumonia it was 1.19 (1.08-1.32) and 1.29 (1.16-1.45) respectively. However, mortality was not elevated with triple therapy among patients with asthma diagnosis (HR 0.99; 95% CI: 0.74-1.34), with two or more prior exacerbations (HR 0.88; 95% CI: 0.70-1.11), and with FEV1 percent predicted >30%. In a real-world setting of COPD treatment, triple therapy initiation was not more effective than dual bronchodilators at preventing all-cause mortality and severe COPD exacerbations. Triple therapy may be unsafe among patients without prior exacerbations, in whom ICS are not recommended, with no asthma diagnosis and with very severe airflow obstruction. Supplemental data for this article is available online at https://doi.org/10.1080/15412555.2021.1977789 .

Discontinuation of inhaled corticosteroids in patients with controlled asthma: The DISCO (Discontinuation of Inhaled Steroid in Controlled asthmatics Over 6 months) study

BackgroundAlthough inhaled corticosteroids (ICSs) are the recommended first-line therapy for asthma, determining whether to continue or discontinue ICS treatment in patients with mild asthma remains challenging for clinicians. Several studies have revealed that patients with mild-persistent asthma maintained a well-controlled state after ICS withdrawal. However, the long-term outcomes of ICS withdrawal have not yet been determined. ObjectiveTo determine the possible clinical outcomes of the discontinuation of ICS in patients with well-controlled mild asthma. MethodsWe investigated the clinical outcomes of discontinuing ICSs in patients with well-controlled mild asthma and compared the time to loss of control (LOC) between patients who stopped ICS treatment (ICS withdrawal group, IWG) and those who continued treatment for 3 years (continuous ICS group, CIG). ResultsA significant difference in the time to LOC was observed between the IWG and CIG (hazard ratio, 2.56; 95% confidence interval, 1.52-4.33; P < .001). Increasing fractional exhaled nitric oxide levels (P = 0.008) and sputum eosinophil counts (%) (P = 0.015) revealed a weak but significant association with LOC risk in the CIG. The sputum eosinophil counts (P = 0.039) and serum total immunoglobulin E levels (P = 0.014) were significantly higher in the LOC group than in the non-LOC group of the CIG. ConclusionOur results suggest that the maintenance of ICS treatment may help keep patients’ asthma under control. Furthermore, patients with LOC had significantly higher sputum eosinophil counts in the CIG than those in the non-LOC group. Therefore, continuous ICS use by patients with mild, well-controlled asthma could be associated with good clinical outcomes. Trial RegistrationClinicalTrials.gov Identifier: KCT0002234.

Effect of Inhaled Corticosteroid Withdrawal on Chronic Obstructive Pulmonary Disease Exacerbations in Patients Taking Triple Therapy at Baseline.

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.

The Clinical Course of Asthma After Withdrawal of Inhaled Corticosteroids

Maintenance of inhaled corticosteroids (ICSs) is recommended in adults with asthma. However, adherence rates in patients with mild asthma and side effects of long-term ICS use can lead to withdrawal. To analyze the real-world outcomes of ICS withdrawal by analyzing data from the Korean National Health Insurance database. Based on claims data from the National Health Insurance of Korea between 2011 and 2014, we identified patients diagnosed with asthma without chronic obstructive pulmonary disease or long-term systemic steroid use who had an ICS medication possession rate of more than 50% in a year. We compared patients who received ICS consistently (maintenance group) with patients who had no ICS prescription for more than 6 months (withdrawal group). We evaluated exacerbation leading to prescription of systemic steroid and emergency department visit or hospitalization. Excluding patients with chronic obstructive pulmonary disease and long-term systemic steroid users, we identified 145,511 patients for the asthma cohort (mean age, 60.0 years; ever-smoker, 63.5%): 132,175 maintained ICS and 13,336 withdrew ICS for more than 6 months. Only 71 patients (0.5%) experienced exacerbation leading to an emergency department visit or hospitalization in the withdrawal group. ICS was restarted within 1 year for 33.6% of the withdrawal group, and 90% of these patients restarted ICS within 158 days. This nationwide study of patients with asthma, characterized by a high proportion of elderly and smokers, showed that ICS withdrawal in about 10% of patients appeared to confer relatively minimal harm and exacerbation leading to hospitalization was not common. Further prospective studies are warranted to carefully explore the safety of ICS withdrawal in younger, nonsmoking, and well-controlled patients with asthma.

Pragmatic trial on inhaled corticosteroid withdrawal in patients with COPD in general practice

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.

Blood eosinophils as a biomarker of future COPD exacerbation risk: pooled data from 11 clinical trials

BackgroundChronic obstructive pulmonary disease (COPD) is characterised by progressive airflow limitation and chronic inflammation. Predicting exacerbations of COPD, which contribute to disease progression, is important to guide preventative treatment and improve outcomes. Blood eosinophils are a biomarker for patient responsiveness to inhaled corticosteroids (ICS); however, their effectiveness as a predictive biomarker for COPD exacerbations is unclear.MethodsThis post hoc analysis pooled data from 11 Boehringer Ingelheim-sponsored Phase III and IV randomised COPD studies with similar methodologies. Exacerbation data were collected from these studies, excluding patients from the ICS withdrawal arm of the WISDOM® study. Patients were grouped according to their baseline blood eosinophil count, baseline ICS use and number of exacerbations in the year prior to each study.ResultsExacerbation rate data and baseline eosinophil count were available for 22,125 patients; 45.6% presented with a baseline blood eosinophil count of ≤ 150 cells/μL, 34.3% with 150–300 cells/μL and 20.1% with > 300 cells/μL. The lowest exacerbation rates were observed in patients with ≤ 150 cells/μL, with small increases in exacerbation rate observed with increasing eosinophil count. When stratified by exacerbation history, the annual rate of exacerbations for patients with 0 exacerbations in the previous year increased in line with increasing eosinophil counts (0.38 for ≤ 150 cells/μL, 0.39 for 150–300 cells/μL and 0.44 for > 300 cells/μL respectively). A similar trend was identified for patients with one exacerbation in the previous year, 0.62, 0.66 and 0.67 respectively. For patients with ≥ 2 exacerbations, exacerbation rates fluctuated between 1.02 (≤ 150 cells/μL) to 1.10 (150–300 cells/μL) and 1.07 (> 300 cells/μL). Higher exacerbation rates were noted in patients treated with ICS at baseline (range 0.75 to 0.82 with increasing eosinophil count) compared with patients not on ICS (range 0.45 to 0.49).ConclusionWe found no clinically important relationship between baseline blood eosinophil count and exacerbation rate. Hence, the current analysis does not support the use of blood eosinophils to predict exacerbation risk; however, previous exacerbation history was found to be a more reliable predictor of future exacerbations.Trial registrationClinicalTrials.gov Identifiers: NCT00168844, NCT00168831, NCT00387088, NCT00782210, NCT00782509, NCT00793624, NCT00796653, NCT01431274, NCT01431287, NCT02296138 and NCT00975195.Graphical abstract

Withdrawal of inhaled corticosteroids in COPD: a European Respiratory Society guideline.

Inhaled corticosteroids (ICS) combined with bronchodilators can reduce the frequency of exacerbations in some patients with chronic obstructive pulmonary disease (COPD). There is evidence, however, that ICS are frequently used in patients where their benefit has not been established. Therefore, there is a need for a personalised approach to the use of ICS in COPD and to consider withdrawal of ICS in patients without a clear indication. This document reports European Respiratory Society recommendations regarding ICS withdrawal in patients with COPD.Comprehensive evidence synthesis was performed to summarise all available evidence relevant to the question: should ICS be withdrawn in patients with COPD? The evidence was appraised using the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach and the results were summarised in evidence profiles. The evidence synthesis was discussed and recommendations formulated by a committee with expertise in COPD and guideline methodology.After considering the balance of desirable and undesirable consequences, quality of evidence, and feasibility and acceptability of interventions, the guideline panel made: 1) conditional recommendation for the withdrawal of ICS in patients with COPD without a history of frequent exacerbations, 2) strong recommendation not to withdraw ICS in patients with blood eosinophil counts ≥300 eosinophils·µL-1 and 3) strong recommendation to treat with one or two long-acting bronchodilators if ICS are withdrawn.A conditional recommendation indicates that there was uncertainty about the balance of desirable and undesirable consequences of the intervention, and that well-informed patients may make different choices regarding whether to have or not have the specific intervention.

Inhaled corticosteroids withdrawal in COPD patients: why, when and how

Inhaled corticosteroids withdrawal in COPD patients: why, when and how

Inhaled Corticosteroid Treatment Regimens and Health Outcomes in a UK COPD Population Study.

BackgroundInhaled corticosteroids (ICS) are a prevailing treatment option for COPD patients but recent guidelines have relegated their use predominantly to patients with frequent exacerbations. Yet large numbers of patients worldwide are currently treated with ICS-containing regimens. We wished to determine in routine clinical practice how common ICS withdrawal is and the differences in health outcomes between patients managed on ICS-containing and non-ICS containing regimens.Patients and MethodsCOPD patients were identified from the UK primary care electronic healthcare records, between 2014 and 2018. Patients were grouped into three treatment regimens: long-acting beta-agonist (LABA) and inhaled corticosteroids (ICS), LABA and long-acting muscarinic antagonist (LAMA), and triple therapy (LABA, LAMA and ICS). Annual incidence of ICS withdrawal was measured. Multivariable logistic regression was used to identify patient factors associated with withdrawal. Multivariable Poisson regression was used to assess the association of exacerbations and hospitalised pneumonia between the ICS-containing regimens (LABA-ICS and triple therapy) and patients prescribed LABA-LAMA.ResultsOf 117,046 patients, around three-quarters were prescribed ICS-containing inhalers but ICS withdrawal occurred annually in only approximately 2–3% of patients. Exacerbations in the past year, but not a past history of pneumonia, were associated with ICS withdrawal. A total of 31,034 patients using three treatment regimens (LABA-ICS, LABA-LAMA or triple therapy) were assessed for their relative risk of exacerbations and pneumonia; the exacerbation risk was slightly lower in LABA-ICS users but the same in triple therapy users, as compared to LABA-LAMA users (LABA-ICS adjusted IRR=0.82 (95% CI 0.73–0.93), triple adjusted IRR=0.99 (95% CI 0.88–1.11)). There was no difference in the pneumonia risk (LABA-ICS adjusted IRR=0.96 (95% CI 0.71–1.31), triple adjusted IRR=1.16 (95% CI 0.87–1.57)).ConclusionUse of ICS-containing inhaled medication is prevalent across the UK while ICS withdrawal from established treatment was relatively uncommon. Exacerbations and pneumonia risk was similar between the ICS-containing and non-ICS containing treatment regimens.