Maintenance Oral Corticosteroids Research Articles

Clinical remission attainment, definitions, and correlates among patients with severe asthma treated with biologics: a systematic review and meta-analysis.

Clinical remission has emerged as an important treatment goal in severe asthma; however, studies have reported variable attainment due to differences in study populations, definitions, and methods. We aimed to perform a systematic review and meta-analysis of clinical remission attainment, definitions, and correlates among patients with severe asthma who have been treated with biologics. In this systematic review and meta-analysis, we searched Web of Science, Embase, and MEDLINE, using the keywords "asthma" and "remission", for studies published between database inception and June 13, 2024, that reported clinical remission among patients with severe asthma treated with biologics. Studies were eligible for inclusion in both the systematic review and meta-analysis if they were published in English language peer-reviewed journals and reported rates of clinical remission for patients treated with biologics for severe asthma. There were no limitations by study design. Two reviewers independently screened identified papers (AS and CR), with disagreements resolved through consensus or referral to a third reviewer (JB). Study-level data on study characteristics, clinical remission definitions, clinical remission attainment, and the potential correlates of clinical remission were extracted independently by two reviewers (AS and CR) using Covidence. We defined a three-component definition of clinical remission, which included use of maintenance oral corticosteroids, exacerbations, and asthma symptom burden, and a four-component definition, which additionally included lung function. We meta-analysed the rate of attainment of clinical remission and assessed the correlates of clinical remission using DerSimonian-Laird random-effects models. Statistical heterogeneity was assessed using the I2 statistic. This study was registered with PROSPERO, CRD42024507233. Our search identified 3014 potentially eligible studies, of which 1812 were screened. 25 studies were included, which reported 28 analyses of clinical remission attainment. 68 definitions of clinical remission were identified, of which 48 were unique. Little consensus was found between studies in terms of the clinical remission definition, particularly for symptoms and lung function. Eight analyses used the three-component definition of clinical remission and 25 used the four-component definition. The pooled proportion of patients who attained clinical remission was 38% (95% CI 29-47; I2=93%) for the three-component definition and 30% (27-34; I2=83%) for the four-component definition. Several pulmonary factors were associated with lower clinical remission rates, including worse FEV1 (odds ratio 0·09 [95% CI 0·01-0·92]; I2=87%), worse asthma symptoms (0·23 [0·17-0·33]; I2=0%), longer asthma duration (0·49 [0·32-0·76]; I2=22%), and use of maintenance oral corticosteroids (0·57 [0·40-0·79]; I2=49%). The presence of comorbidities, in particular depression (0·38 [0·23-0·61]; I2=6%) and obesity (0·41 [0·31-0·54]; I2=0%), were important non-pulmonary barriers to clinical remission. Clinical remission is an achievable goal for a minority of patients with severe asthma treated with biologics. Definitions of clinical remission varied substantially between studies, and materially affected attainment, suggesting an urgent need for further consensus-driven definitions. Longer disease duration, higher asthma severity, and the presence of comorbidities were identified as important barriers to clinical remission, suggesting that earlier intervention with effective treatments and a broader treatable traits approach might improve outcomes. Health Data Research UK, Inflammation and Immunity driver project.

Patient-centred composite scores as tools for assesment of response to biological therapy for paediatric and adult severe asthma.

We have previously developed Core Outcome Measures sets for Severe Asthma (COMSA) by multi-stakeholder consensus. There are no patient-centred tools to quantify response to biologics for severe asthma. We aimed to develop paediatric and adult CompOsite iNdexes For Response in asthMa (CONFiRM) incorporating clinical parameters and patient-reported quality of life (QoL). International expert healthcare professionals (HCPs) and patients with severe asthma were invited to: 1) develop consensus levels of clinically relevant changes for each outcome measure within COMSA; 2) use multicriteria decision analysis to develop the CONFiRM scores and 3) assess their internal validity. A separate group of HCPs evaluated CONFiRM's external validity. Five levels of change for each COMSA outcome were agreed. Severe exacerbations and maintenance oral corticosteroids use were rated as most important in determining both paediatric and adult CONFiRM scores. There was strong agreement between HCPs and patients, although patients assigned greater importance to QoL. The CONFiRM score quantified response to a biological from -31 (deterioration) to 69 (best possible response). Paediatric and adult CONFiRMs had good discriminative ability for a sufficient (AUC≥0.92) and a substantial (AUC≥0.95) response to biologics. Both CONFiRMs demonstrated excellent external validity (Spearman correlation coefficients 0.9 and 0.8 for paediatric and adult respectively (p<0.0001)). We have developed novel patient-centred paediatric and adult CONFiRMs which include QoL measures. CONFiRMs should allow a more holistic understanding of response for the patient and a standardised assessment of the effectiveness of biologics between studies. Further research is needed to prospectively validate CONFiRM scores.

Maintenance OCS Were Used More Frequently Than Biologics in Patients with Uncontrolled GINA 4/5 Asthma in Germany in 2019.

Asthma is affecting 4-5% of all adults (10% of children) in Germany, ≥ half are inadequately controlled. In 2019 up to 54 thousand patients suffered from severe uncontrolled asthma, 52% were treated/co-treated by pneumonologists. 45% of them had continuous oral corticosteroid (OCS)- and short-acting β2-agonist (SABA) overuse for ≥2 years. The aim of the current study was to analyze the main treatments, escalation schemes and the adherence to the GINA recommendations. Retrospective analysis in 2021 based on data from January to December 2019 in Germany, using the IQVIA™ LRx prescription database and the IQVIA™ Disease Analyzer database containing anonymized electronic medical records as the main data sources. In 2019 25,200 patients with severe, uncontrolled asthma treated in a pneumonologist´s practice in Germany received GINA 3 (0,4%), GINA 4 (76%) or GINA 5 therapy (24%) during the study year compared to 59% GINA 5 therapy in the 5-10% (1,500-3,000) co-treated in a specialized outpatient department. In Pneumonologists` practices the most frequent choice in GINA 5 was OCS in 69% of patients (biologicals 37%, long-acting muscarinic antagonist (LAMA) 20%) compared to 66% biologicals, 55% OCS, and 25% LAMA in the outpatient department. 54,958 of 613,000 GINA 4/5 patients were treated with OCS, 9,725 even with doses above the so called "Cushing threshold" for prednisolone of 2700 mg/year. After introduction of a biological treatment, patients reduced their SABA prescriptions by 28%, OCS by 55%, and OCS overall exposure by 40%, one-third did not need OCS anymore. In 75% of patients with uncontrolled asthma for ≥2 years therapy was not escalated beyond GINA 4 or low dose OCS was used as the most frequent add-on treatment in GINA 5 contradictory to treatment recommendations. Use of biologics reduced on demand rescue medication and OCS use.

Clinical remission in patients with biologic-naïve asthma: a multicenter study in Japan

BackgroundClinical remission (CR) is a new realistic management goal for patients with asthma, regardless of the disease severity. ObjectiveTo investigate the rate of achievement of CR in patients treated with inhaled corticosteroid/long-acting β2-agonist (ICS/LABA) and non-biologics, and the characteristics of patients who achieved CR. MethodsWe performed a post hoc analysis from a multicenter, cross-sectional survey in Japan. 3-way CR was defined as the absence of exacerbation, no use of maintenance oral corticosteroids, and the absence of significant asthma symptoms (5-item Asthma Control Questionnaire [ACQ] < 1.5). We defined 4-way CR as 3-way CR plus having normalized lung function (forced expiratory volume [%FEV1] ≥ 80%). Deep remission (DR) was defined as 4-way CR plus suppressed type-2 airway inflammation (fractional exhaled nitric oxide [FeNO] < 35 ppb). ResultsThe criteria for 3-way CR, 4-way CR, and DR were met by 56.9%, 35.0%, and 24.7% of patients, respectively. Compared to patients who achieved the 3-way CR, unachieved patients have lower %FEV1 (77.6% vs. 85.4%, p<0.0001), higher FeNO levels (42 ppb vs. 34 ppb, p=0.0182), and there were more discordances in asthma control perception between patient-physicians (38.5% vs. 9.3%, p<0.0001). Physician-patient discordance was an independent factor that prevented the achievement of the 3-way CR in the logistic regression analysis, even when adjusted for %FEV1 and FeNO (odds ratio 0.397, p<0.0001). ConclusionAchieving CR in patients treated with ICS/LABA without biologics is challenging. Discrepancies between patient and physician perceptions on asthma control are significant barriers to achieving CR.

Sub-Optimal Disease Control and Low Blood Eosinophil Testing Frequency in Chinese Adult Patients with Asthma Receiving GINA Step 4/5 Treatment: A Real-World Study.

To inform effective management strategies for severe asthma in China, this study aimed to comprehensively characterize clinical characteristics, treatment patterns, disease control status, and healthcare resource utilization among patients on GINA Step 4/5 therapies by analyzing data from the Adelphi Asthma Disease Specific Program conducted in China. All information was retrieved from medical records or collected from physicians and patients on the survey date (August-December 2018); no follow-up was conducted. Results were summarized descriptively for patients on GINA Step 4/5 therapies, who were pooled from a consecutive sample (comprising three or more consecutive patients with physician-diagnosed asthma from each participating physician) and an oversample (comprising the next two patients with physician-perceived severe asthma from each participating physician). Of the included patients (n=754), 51.5% had ever had a blood eosinophil measurement taken, 22.1% had available records for their most recent blood eosinophil measurements (68.9% of them had an elevated level ≥150 cells/µL), 39.9% had ever been tested for specific immunoglobulin E or radioallergosorbent, and 8.0% were prescribed maintenance oral corticosteroids. Asthma was not well controlled in 69.2% of patients. In the prior year, 27.1% experienced at least one severe exacerbation and 22.8% experienced at least one hospitalization (emergency visit or overnight stay) due to asthma. In Chinese patients with asthma on GINA Step 4/5 therapies, biomarker testing was underutilized, asthma was not well controlled, and severe exacerbations were not infrequent. These findings highlight the urgent need for optimized asthma management for patients on GINA Step 4/5 therapies in China.

Prospective REALITI-A Study: 2-Year Real-World Benefits of Mepolizumab in Severe Asthma

BackgroundMepolizumab, a monoclonal antibody targeting interleukin-5, is of proven clinical benefit in severe asthma; prospective, long-term, real-world data in severe asthma are required. Research QuestionThis study aimed to assess the real-world benefit of 2 years’ mepolizumab treatment in severe asthma. Study Design and MethodsREALITI-A was a 2-year, international, prospective study enrolling adults with asthma, newly initiating mepolizumab 100 mg subcutaneously (physician decision). Outcomes in the 1-year pre-mepolizumab versus 2-year follow-up periods included rates of clinically significant asthma exacerbations (CSE; deterioration requiring systemic corticosteroids and/or emergency department [ED] visit/hospitalisation), exacerbations requiring ED visit/hospitalisation, exacerbations requiring hospitalisation, proportion of patients with no exacerbations, median daily maintenance oral corticosteroid (mOCS) dose, proportion of patients discontinuing mOCS completely, asthma control questionnaire (ACQ)-5 score, forced expiratory volume in 1s (FEV1) and adverse events (AEs). ResultsAfter 2 years’ follow-up, 73% of patients (n=599/822) had no record of mepolizumab discontinuation. During the 2-year follow-up versus pre-mepolizumab period (N=822), rates of CSEs, exacerbations requiring ED visit/hospitalisation, or hospitalisation only were reduced by 74%, 79% and 73%, respectively (odds ratio for no CSEs: 10.0; 95% confidence interval: 7.55, 13.25). Median (Q1, Q3) daily mOCS dose decreased from 10.0 (5.0, 14.7) mg at Week 0 (n=297) to 0.0 (0.0, 5.0) mg at Weeks 101–104 (n=168), and the proportion of patients discontinuing mOCS increased progressively to 43% at 1 year and 57% at 2 years. There was a 1.53-point reduction in ACQ-5 scores from baseline at 2 years. At Months 21–24, least square mean FEV1 improved by 142 mL from baseline. Ninety (11%) and 7 (<1%) patients experienced mepolizumab-related AEs and serious AEs during the follow-up period, respectively. InterpretationIn patients with severe asthma, real-world mepolizumab treatment for 2 years was well-tolerated, and was associated with sustained reductions in exacerbations and progressive reductions in mOCS use.

Titration of anti-IL-5 biologics in severe asthma: an open-label randomised controlled trial (the OPTIMAL study).

Anti-interleukin (IL)-5 biologics effectively reduce exacerbations and the need for maintenance oral corticosteroids (mOCS) in severe eosinophilic asthma. However, it is unknown how long anti-IL-5 treatment should be continued. Data from clinical trials indicate a gradual but variable loss of control after treatment cessation. In this pilot study of titration, we evaluated a dose-titration algorithm in patients who had achieved clinical control on an anti-IL-5 biologic. In this open-label randomised controlled trial conducted over 52 weeks, patients with clinical control (no exacerbations or mOCS) on anti-IL-5 treatment were randomised to continue with unchanged intervals or have dosing intervals adjusted according to a titration algorithm that gradually extended dosing intervals and reduced them again at signs of loss of disease control. The OPTIMAL algorithm was designed to down-titrate dosing until signs of loss of control, to enable assessment of the longest dosing interval possible. Among 73 patients enrolled, 37 patients were randomised to the OPTIMAL titration arm; 78% of patients tolerated down-titration of treatment. Compared to the control arm, the OPTIMAL arm tended to have more exacerbations during the study (32% versus 17%; p=0.13). There were no severe adverse events related to titration, and lung function and symptoms scores remained stable and comparable in both study arms throughout. This study serves as a proof of concept for titration of anti-IL-5 biologics in patients with severe asthma with clinical control on treatment, and the OPTIMAL algorithm provides a potential framework for individualising dosing intervals in the future.

Impact of comorbidities on EQ-5D quality-of-life index in severe asthma

BackgroundSevere asthma pathology encompasses a wide range of pulmonary and extra-pulmonary treatable traits with a high prevalence of comorbidities. Although asthma-specific health related quality of life measures are most sensitive to changes in asthma control, generic measures, such as EQ-5D-5L (EuroQol 5-Dimension 5-Level questionnaire), are potentially better for capturing the impact of comorbidities. ObjectiveTo examine the impact of pulmonary and extra-pulmonary treatable traits on quality of life at initial severe asthma assessment, and to compare the characteristics of those patients whose quality of life does and does not improve during follow-up at severe asthma centres. MethodsPatients characteristics at baseline assessment within the UK Severe Asthma Registry were compared by EQ-5D-5L utility index quartile. Patients with follow-up review data were stratified by change in EQ-5D-5L utility index from baseline to follow-up, and characteristics similarly examined. ResultsPatients in the quartiles with worst dysutility at baseline were observed to exhibit more treatable traits and in particular extra-pulmonary traits associated with cumulative systemic corticosteroids, including obesity, anxiety/depression, and osteoporosis. In those patients whose quality of life improved over follow-up, a reduction in exacerbations, uncontrolled symptoms and requirement for maintenance oral corticosteroids (OCS) was observed. ConclusionBoth pulmonary and extra-pulmonary treatable traits are important determinants of quality of life in severe asthma. Comorbidities associated with cumulative systemic corticosteroid exposure are particularly associated with worse quality of life, emphasising the importance of early identification and management of severe asthma before comorbidities develop.

Biomarker Predictors of Clinical Efficacy of the Anti-IgE Biologic Omalizumab in Severe Asthma in Adults: Results of the SoMOSA Study.

Background: The anti-IgE monoclonal antibody omalizumab is widely used for severe asthma. This study aimed to identify biomarkers that predict clinical improvement during 1 year of omalizumab treatment. Methods: One-year open-label Study of Mechanisms of action of Omalizumab in Severe Asthma (SoMOSA) involving 216 patients with severe (Global Initiative for Asthma step 4/5) uncontrolled atopic asthma (at least two severe exacerbations in the previous year) taking high-dose inhaled corticosteroids and long-acting β-agonists with or without maintenance oral corticosteroids. It had two phases: 0-16 weeks, to assess early clinical improvement by Global Evaluation of Therapeutic Effectiveness (GETE); and 16-52 weeks, to assess late responses based on ⩾50% reduction in exacerbations or mOCS dose. All participants provided samples (exhaled breath, blood, sputum, urine) before and after 16 weeks of omalizumab treatment. Measurements and Main Results: A total of 191 patients completed phase 1; 63% had early improvement. Of 173 who completed phase 2, 69% had reduced exacerbations by ⩾50% and 57% (37 of 65) taking mOCSs had reduced their dose by ⩾50%. The primary outcomes 2,3-dinor-11-β-PGF2α, GETE score, and standard clinical biomarkers (blood and sputum eosinophils, exhaled nitric oxide, serum IgE) did not predict either clinical response. Five volatile organic compounds and five plasma lipid biomarkers strongly predicted the ⩾50% reduction in exacerbations (receiver operating characteristic areas under the curve of 0.780 and 0.922, respectively) and early responses (areas under the curve of 0.835 and 0.949, respectively). In an independent cohort, gas chromatography/mass spectrometry biomarkers differentiated between severe and mild asthma. Conclusions: This is the first discovery of omics biomarkers that predict improvement in asthma with biologic agent treatment. Prospective validation and development for clinical use is justified.

Oral corticosteroid stewardship: key insights from the Australasian Severe Asthma Registry.

People with severe asthma remain at risk of toxicity from maintenance oral corticosteroid (OCS) use and/or frequent OCS burst therapy. Cumulative exposures above 500-1000 mg prednisolone are associated with adverse effects, and recently OCS stewardship principles were promulgated to guide OCS prescription. To examine real-world registry data to quantify OCS burden, ascertain trends over time in prescription and assess whether opportunities to implement steroid-sparing strategies were utilised. Participants were enrolled in the Australasian Severe Asthma Registry for the period 2013-2021. Assessments were taken at enrolment and then annual follow-up, which included asthma control and OCS use. Descriptive analyses were performed, and subgroups were compared at baseline and over time. Nine hundred and twenty-four participants were evaluated and 215/924 (23%) were taking maintenance OCS at baseline,with 44% and 32% of participants having exposure to ≥500 or 1000 mg of OCS respectively in the prior year. Twelve months later, an additional 10% and 9% of participants reached cumulative doses of 500 or 1000 mg. People exceeding thresholds had ongoing poor asthma control. At baseline, 240/924 (26%) people were treated with asthma biological therapy. An additional 83 (12%) participants were identified as potentially benefiting from this steroid-sparing medication. Of these patients, only 23% commenced a biologic agent in the next 12 months. A large national asthma registry identifies exposure to toxic cumulative doses of OCS in more than a third of participants, with further subsequent cumulative dose escalation over 2 years. Steroid-sparing strategies were often not employed, highlighting the need for implementation of OCS stewardship initiatives.

Long-Term Effectiveness of Anti-IL-4R Therapy Following Suboptimal Response to Anti-IL-5/5R Therapy in Severe Eosinophilic Asthma

Dupilumab is an anti-IL-4R monoclonal antibody (mAb) with proven efficacy in severe eosinophilic asthma (SEA). A suboptimal response to anti-IL-5/5R mAbs is seen in some patients with ongoing evidence of type 2 (T2) inflammation. To understand whether targeting IL-13 pathways with dupilumab in these patients may lead to better clinical outcomes. We performed a retrospective analysis of the extended clinical effectiveness of dupilumab up to 2 years of treatment in patients with SEA who had not responded adequately to anti-IL-5/5R biologics. The ability to achieve clinical remission and the change in the remission domains of exacerbation rate (AER), maintenance oral corticosteroid dose (mOCS), lung function (forced expiratory volume in 1 second), and asthma control (Asthma Control Questionnaire 6) were recorded. Thirty-seven patients (mean age 41 years, 70% female) were included in the analysis. The mean (standard deviation) AER fell by almost 90% from 3.16 (1.28) at dupilumab initiation to 0.35 (0.72) after 1 year. The median (interquartile range) mOCS dose (n= 20) fell from 10 (5-25) mg to 0 (0-5) mg at 1 year, with 14 of 20 (70%) able to stop prednisolone altogether. Clinical remission was achieved in 16 of 37 (43%). Patients who achieved remission had a higher pre-IL-5/5R fractional exhaled nitric oxide (FeNO) level (85 [39-198] parts per billion [ppb] vs 75 [42-96] ppb, P= .03). Significant improvements in clinical outcomes are possible after a switch to dupilumab in patients experiencing a suboptimal response to anti-IL-5/5R therapies. A higher FeNO in poor responders to anti-IL-5/5R who achieve remission with dupilumab is suggestive of an IL-13-driven subphenotype of T2-high asthma in which the eosinophil appears unlikely to play a key role in the disease pathogenesis.

Benralizumab in severe eosinophilic asthma by previous biologic use and key clinical subgroups: real-world XALOC-1 programme.

Pivotal phase 3 trials and real-world studies have demonstrated benralizumab's overall efficacy and safety in severe eosinophilic asthma (SEA). Additional large-cohort data are needed to confirm its real-world effectiveness in SEA according to previous biologic use and key baseline characteristics important for treatment selection. XALOC-1 is a large, multinational, retrospective, observational, real-world study programme of benralizumab in adults with SEA. This 48-week integrated analysis assessed annualised exacerbation rate (AER), maintenance oral corticosteroid (mOCS) use, asthma symptom control and lung function during a 12-month baseline period and up to 48 weeks after benralizumab initiation. Subgroup analyses were based on previous biologic use and key baseline clinical characteristics (mOCS use, blood eosinophil count, exacerbation history, age at asthma diagnosis, fractional exhaled nitric oxide level and presence of atopy and chronic rhinosinusitis with nasal polyps). Out of 1002 patients analysed, 380 were biologic-experienced. At week 48, 71.3% were exacerbation-free (versus 17.2% at baseline); relative reduction in AER was 82.7% overall and 72.9% in biologic-experienced patients; rates were maintained across all key clinical characteristic subgroups. Of patients using mOCS at baseline (n=274), 47.4% (130 out of 274) eliminated their use by week 48; the mean reduction from baseline in daily dose was 51.2% and, notably, 34.9% in biologic-experienced patients (n=115). Clinically significant improvements in asthma symptom control and lung function were observed. In this large, real-world programme, SEA patients treated with benralizumab had substantial improvements in clinical outcomes irrespective of previous biologic use and key clinical characteristics important to therapeutic decision-making in clinical practice.

Clinical characteristics of complete responders versus non-complete responders to omalizumab, benralizumab and mepolizumab in patients with severe asthma: a long-term retrospective analysis

Background Some patients with severe asthma may benefit from treatment with biologics, but evidence has been mostly collected from randomized controlled trials (RCTs), in which patients’ characteristics are different from those encountered in asthma patients in the real-world setting. The aim of this study was to describe the clinical features of complete responders versus non-complete responders to long-term treatment with biologics in patients with severe asthma attended in routine daily practice. Methods Data of a cohort of 90 patients with severe asthma who were treated with biologics (omalizumab, benralizumab, and mepolizumab) for at least 12 months and were followed up to March 2022. Data recorded included clinical characteristics and effectiveness of treatment (exacerbation, Asthma Control Test [ACT] score, lung function, use of maintenance oral corticosteroids [mOCS]), FeNO, and blood eosinophils at baseline, at 12 months, and at the end of follow-up. Complete response is considered if, in addition to not presenting exacerbations or the use of mOCS, the ACT score was >20 and, the FEV1 >80% predicted. Results An improvement in all asthma control parameters was observed after 12 months of treatment and a mean follow-up of 55 months. After 12 months of treatment 27.2% of patients met the criteria of complete response and this percentage even increased to 35.3% at the end of follow-up. Long-term complete response was associated to better lung function with mepolizumab and omalizumab treatment and to less previous exacerbations in the benralizumab group. The main cause of not achieving a complete response was the persistence of an airflow obstructive pattern. Conclusions This study shows that omalizumab, benralizumab, and mepolizumab improved the clinical outcomes of patients with severe asthma in a clinic environment with similar effect sizes to RCTs in the long term follow-up. Airflow obstruction, however, was a predictor of a non-complete response to biologics.

Super-responder and clinical remission in patients with asthma on treatment with single biologic therapy or cycling therapy using dupilumab in a real-world setting.

Regarding the therapeutic target in asthma, super-responder status (SR) is a status without systemic corticosteroids. Recently, clinical remission (CR), being a status of prolonged absence of asthma symptoms without systemic corticosteroids and/or normal pulmonary function, has gained attention as a new therapeutic target in asthma. Here, we examined the percentage and features of asthma patients on treatment with dupilumab showing SR and CR. 49 asthma patients used subcutaneous dupilumab for >1 year between April 2019 and November 2022. The status of SR and CR for 1 year was evaluated. Patients without any maintenance oral corticosteroids and exacerbations requiring systemic corticosteroids were classified as SR. CR was defined using three definitions based on changes in asthma symptoms and pulmonary function in addition to achieving SR for 1 year: CR without pulmonary function criteria (CR w/o F), fulfilment of asthma symptom improvement (asthma control questionnaire score <0.75 or asthma control test score ≥23); and CR-70 or CR-80, pulmonary function improvement (%forced expiratory volume in 1 second ≥70% or ≥80%) in addition to achieving CR w/o F, respectively. 38 (77.6%), 22 (44.9%), 13 (26.5%), 12 (24.5%) of patients had SR, CR w/o F, CR-70, and CR-80, respectively. Severe eosinophilic chronic rhinosinusitis was significantly more found in patients with SR and CR based on all three definitions than in those without. This study identified the percentage and features of patients on treatment with dupilumab showing SR and CR in a real-world setting. The outcome beyond CR on biologic treatment should be clarified.

Impact of sex on severe asthma: a cross-sectional retrospective analysis of UK primary and specialist care

IntroductionAfter puberty, females are more likely to develop asthma and in a more severe form than males. The associations between asthma and sex are complex with multiple intrinsic and external...

Real-World Characteristics of Patients with Severe Asthma prior to Starting Dupilumab: The ProVENT Study

Introduction: Dupilumab is approved for the treatment of severe type 2 (T2) asthma; however, the characteristics of patients receiving dupilumab in routine clinical practice are incompletely understood. This study describes the characteristics of patients with severe asthma before dupilumab treatment in a real-world setting. Methods: This interim analysis of an ongoing real-life study of dupilumab assessed baseline characteristics of the first patient cohort enrolled in the ProVENT study. Results: A total of 99 patients (59% females) were analyzed (17% received another biologic before dupilumab treatment and 15% were on maintenance oral corticosteroid treatment). Adult-onset asthma (>18 years) and an allergic phenotype were documented in 58% and 48% of patients, respectively. Median (interquartile range) age was 54 (40–61) years; the median number of exacerbations in the last 24 months was 1 (0–3); median fractional exhaled nitric oxide (FeNO) value was 38 (23–64) ppb; and median blood eosinophils (bEOS) count was 184 (8–505) cells/µL. According to the United Kingdom Severe Asthma Registry classification, 53% of patients had T2 intermediate asthma (bEOS ≥150 cells/µL or FeNO ≥25 ppb), 17% had T2 high asthma (bEOS ≥150 cells/µL and FeNO ≥25 ppb), and 4% had T2 low asthma (bEOS <150 cells/µL and FeNO <25 ppb). At least one GINA criterion for T2 airway inflammation was documented in 70% of patients. T2 comorbidities were observed in 64% of patients. Conclusions: This analysis suggests that patients eligible for dupilumab treatment display various clinical and biochemical characteristics rather than one clear-cut phenotype.

Factors influencing poor response to type 2 targeted therapies in severe asthma: a retrospective cohort study

BackgroundA significant breakthrough has been made in treating severe asthma, with the recognition of various asthma phenotypes and an updated management guideline. Type 2 targeted therapies, such as benralizumab and omalizumab; have been identified as an effective treatment for severe asthma, improving patient response, lung function tests and asthma symptom control. This study aimed to evaluate factors contributing to poor response to therapy.MethodsA retrospective single-center cohort study of 162 patients with severe asthma who started biologic therapy; their data were retrieved from medical records for further analysis. Poor responders were patients remained clinically and functionally uncontrolled despite even after augmenting all treatment options.ResultsChildhood-onset asthma, bronchiectasis, poor symptom control (ACT below 19), severe airway obstruction (< 60% predicted), and maintenance oral corticosteroid (mOCS) use were significantly associated with poor response to omalizumab and benralizumab; p = 0.0.4 and 0.01; 0.003 and 0.01; 0.01 and 0.001, 0.05 and 0.04; 0.006 and 0.02, respectively. However, chronic rhinosinusitis and IgE < 220kIU/L were associated with higher poor response rates to omalizumab (p = 0.01 and 0.04, respectively). At the same time, female patients and those with blood eosinophils level < 500 cells/mm3 had a higher poor response rate to benralizumab (p = 0.02 and 0.01, respectively). Ischemic heart disease (IHD), bronchiectasis, and continued use of OCS increased the likelihood of poor response to omalizumab by 21, 7, and 24 times (p = 0.004, 0.008, and 0.004, respectively). In contrast, the female gender, childhood-onset asthma and higher BMI increased the likelihood of poor response to benralizumab by 7, 7 and 2 times more, p = 0.03, 0.02 and 0.05, respectively.ConclusionPoor response to omalizumab treatment was independently associated with ischemic heart disease (IHD), bronchiectasis, and a history of maintenance oral corticosteroid (mOCS) use. Conversely, poor response to benralizumab therapy was independently linked to female gender, childhood-onset asthma and higher body mass index (BMI).

Efficacy and Safety of Biologics for Oral Corticosteroid–Dependent Asthma: A Systematic Review and Network Meta-Analysis

A maintenance oral corticosteroid (OCS) in addition to high-dose inhaled corticosteroids plus long-acting β2-agonists in patients with severe asthma leads to long-term adverse events. Oral corticosteroid-sparing agents are of high priority. This network meta-analysis assessed biologics' comparative efficacy and safety in OCS-dependent patients with asthma. We performed a systematic search through PubMed, Scopus, Embase, the Cochrane Center of Controlled Trials, and Google Scholar for randomized controlled trials that addressed the efficacy and safety of biologics compared with placebo in OCS-dependent patients with asthma from inception to July 2023. The primary outcome was an overall reduction in the OCS dose while asthma control was maintained. We included seven randomized controlled trials involving 1,052 OCS-dependent patients with asthma. Compared with placebo, benralizumab every 8 weeks, benralizumab every 4 weeks, dupilumab, and mepolizumab were efficacious in achieving a reduction in the OCS dose with low to moderate confidence (odds ratio [95% CI]: 4.12 [2.22-7.64]; 4.09 [2.22-7.55]; 3.25 [1.90-5.55]; and 2.39 [1.25-4.57], respectively) whereas tralokinumab, tezepelumab, and subcutaneous reslizumab were ineffective. An indirect comparison found no significant differences among benralizumab, dupilumab, and mepolizumab. Efficacy in reducing exacerbations was consistent with the primary analysis. High baseline blood eosinophil counts benefit from anti-IL-5 therapies, whereas high FeNO levels favor dupilumab regardless of blood eosinophil counts. Adverse events between biologics and placebo were comparable, except for eosinophilia with dupilumab. In OCS-dependent patients with asthma, benralizumab, dupilumab, and mepolizumab were superior to placebo in reducing the OCS dose. Evaluating baseline biomarkers helps in choosing the proper biologics to maximize treatment effects.

Tobacco Exposure and Efficacy of Biologic Therapy in Patients With Severe Asthma: A Nationwide Study From the Danish Severe Asthma Register

Randomized trials of biologics in severe, uncontrolled asthma have excluded patients with a cumulative tobacco exposure of more than 10 pack-years. Therefore, our knowledge of the impact of smoking exposure on the clinical effects of biologics in severe asthma remains incomplete. However, because many patients with asthma are current or former smokers, investigating the potential impacts of tobacco exposure on the effects of biologic treatment is clinically important. To investigate the impact of smoking history and tobacco exposure on the effectiveness of biologic therapy in real-life patients with severe asthma. We used data from a complete nationwide cohort of patients with severe asthma who were receiving biologics, the Danish Severe Asthma Register. We divided patients according to smoking history and cumulative tobacco exposure and analyzed data at baseline and after 12 months of biologic treatment. A total of 724 bio-naive patients were identified in the Danish Severe Asthma Register, 398 of whom had never been smokers (55%), 316 were previous smokers (44%), and 10 were current smokers (1%). Within the group of current and former smokers, 37% had 1 to 9 pack-years of tobacco exposure, 26% had 10 to 19 pack-years, and 37% had 20 or more pack-years of tobacco exposure. Patients with tobacco exposure had similar reductions in the number of exacerbations, reductions in maintenance oral corticosteroid use, and improvements in asthma symptoms compared with patients with 0 pack-years. Former smoking history and lifetime tobacco exposure do not have an impact on the efficacy of biologics in patients with severe asthma.

Real-world super-response to biologics in severe asthma: A French monocentric retrospective cohort study

BackgroundBiologics have dramatically improved outcomes in severe T2-high asthma. Although the identification of patients with the best response is key to understand the efficacy of these agents and select the best target populations, the definition and predictors of super-response are not fully established yet. MethodsThis study aimed to describe super-response and to identify predictors of super-response to biologics in a French severe eosinophilic asthma cohort followed in a severe asthma tertiary care center between January 2005 and December 2020. Super-response was defined a priori as no oral corticosteroids intake and no exacerbations over 12 months. Collected data at baseline and after 12 months included asthma history, comorbidities, clinical characteristics, lung function, T2-biomarkers, baseline asthma-related treatments, and asthma control. ResultsAmong 157 patients assessed for eligibility, 108 were included, corresponding to 166 treatments with biologics. Overall response rate was 63.2 % (105/166) and super-response rate was 39.7 % (66/166). In omalizumab group (n = 67), lower dose of oral corticosteroids in maintenance was the only factor associated with super-response (p = 0.008). In the anti-IL-5/anti-IL-5R group (n = 99), absence or lower dose of oral corticosteroids in maintenance and absence of eosinophilic granulomatosis with polyangiitis were statistically associated with super-response (p = 0.009, p = 0.001 and p = 0.02 respectively). ConclusionIn this real-life study in severe T2-high asthma patients, a lower dose or absence of daily oral corticosteroids and absence of eosinophilic granulomatosis with polyangiitis were the only identifiable predictors of super-response to biologics. Physicians should not wait for maintenance oral corticosteroids to be required before considering the initiation of a biologic in severe asthma.