Reduced Exacerbation Rates Research Articles

Use of Targeted Biologic Therapies in Asthma: Current Practice in India

Asthma remains a significant public health issue in India, with a growing number of patients experiencing severe and uncontrolled forms of the disease. Targeted biologic therapies, including omalizumab, mepolizumab, benralizumab, reslizumab, and dupilumab, have emerged as advanced treatment options for patients with severe asthma, especially those with allergic or eosinophilic phenotypes. These therapies work by targeting specific immunological pathways involved in asthma pathogenesis, offering better symptom control and reducing exacerbation rates. However, the high cost of biologics, limited access, and inconsistent insurance coverage pose significant barriers to their widespread use in India. Despite these challenges, real-world data from Indian studies demonstrate promising clinical outcomes with biologic therapies in patients with difficult-to-treat asthma. This review examines the current landscape of biologic use in India, challenges related to cost and accessibility, and future prospects for integrating these treatments into routine asthma care, particularly through cost- reduction strategies and expanded healthcare coverage.

Reduced Effectiveness of Anti-IgE Treatment Among Adults with Severe Asthma with Older Age of Asthma Onset: Results from the CHRONICLE Study.

Younger age of asthma onset (AAO) has been associated with an allergic phenotype, whereas eosinophilic phenotypes have been associated with older AAO. In randomized trials, biologic efficacy among adults with severe asthma (SA) has varied by age at asthma onset. To determine whether these associations observed in trials apply to real-world outcomes, this study examined biologic effectiveness by AAO and biologic class in a large, real-world cohort. CHRONICLE is an ongoing, real-world study of US adults with subspecialist-treated SA receiving biologics, maintenance corticosteroids, or who are uncontrolled on high-dosage inhaled corticosteroids with additional controllers. Patients enrolled between February 2018 and February 2022 who initiated a biologic for SA and had complete data for analysis were included. A locally estimated scatterplot smoothing (LOESS) analysis was used to plot the relationship between percentage exacerbation rate reduction and AAO by biologic class. Of 578 patients with complete data, 198, 149, and 231 were diagnosed with asthma at age <18, 18-39, and ≥40 years, respectively. Across subgroups, patients were predominantly White (72-78%), female (67-73%), and commercially insured (54-71%). In the LOESS analysis, exacerbation rate reductions were similar for anti-IgE and anti-IL-5/5R and anti-IL-4R subgroups with younger AAO, but the exacerbation rate reduction diminished for patients with older AAO receiving anti-IgE therapy, particularly with asthma onset age ≥40 years. Clinicians should consider age of onset in biologic treatment decisions, given reduced effectiveness of omalizumab in patients with asthma onset at age ≥40 years. NCT03373045.

Dupilumab reduces exacerbations and improves lung function in patients with chronic obstructive pulmonary disease and emphysema: Phase 3 randomized trial (BOREAS)

BackgroundDupilumab, a fully human monoclonal antibody that blocks the shared receptor component for interleukin-4 and interleukin-13, reduced exacerbations and improved lung function in patients with chronic obstructive pulmonary disease (COPD) and type 2 inflammation in the phase 3 BOREAS trial. ObjectiveTo assess clinical outcomes in patients from BOREAS by emphysema status. MethodsPatients with COPD and type 2 inflammation (screening blood eosinophils ≥300 cells/μL) on maximal inhaled therapy were randomized to add-on dupilumab 300 mg or placebo every 2 weeks for 52 weeks. We assessed the annualized moderate/severe COPD exacerbation rates over 52 weeks and change from baseline to Week 12 in prebronchodilator forced expiratory volume in 1 second (FEV1) in patients with and without investigator-reported emphysema. ResultsInvestigator-reported emphysema was present in 306/939 patients (32.6%) at baseline. Dupilumab reduced exacerbation rates vs placebo by 29% (relative risk [RR] 0.71 [95% CI 0.53–0.95]) and 31% (RR 0.69 [95% CI 0.53–0.89]) in patients with and without emphysema, respectively. Prebronchodilator FEV1 least squares mean difference from baseline to Week 12 for dupilumab vs placebo was 0.07 L ([95% CI 0.002–0.14]) and 0.09 L ([95% CI 0.04–0.14]) in patients with and without emphysema, respectively. No treatment by emphysema interaction effect was observed for the annualized rate of exacerbations (P value for interaction = 0.8296) or change in prebronchodilator FEV1 (P value for interaction = 0.6438). ConclusionDupilumab efficacy was similar in patients with COPD and type 2 inflammation, with or without investigator-reported emphysema.

Tezepelumab: a promising therapy for severe uncontrolled asthma

Asthma is a complex inflammatory airway disease affecting a significant global population, spanning from childhood through adulthood. Despite advances in treatment modalities, a significant subset of patients, approximately 10%, grapple with severe asthma, characterized by increased healthcare utilization and diminished quality of life. Tezepelumab, a monoclonal antibody targeting thymic stromal lymphopoietin (TSLP), offers promising therapeutic potential. TSLP is a protein released by a variety of cells, with a predominance of epithelial cells, in reaction to plenty of stimuli, such examples as viruses, aeroallergens, and others. Its action is upstream and pertains to initiating numerous subsequent innate and adaptive immune reactions, contributing to the continuation of asthma pathophysiological processes. Tezepelumab’s unique efficacy spans diverse severe asthma phenotypes, significantly reducing exacerbation rates across eosinophilic and non-eosinophilic subtypes. Its favorable safety profile and clinically meaningful improvements in asthma control, accompanied by reductions in cytokine levels and baseline biomarkers, underscore its broad impact on asthma inflammation. Its efficacy, irrespective of type 2 (T2) endotype, reinforces the idea that TSLP blockade broadly inhibits pathways crucial to asthma pathophysiology, rather than narrowly focusing on individual downstream factors, as previous biological treatments have. This review discusses the rationale for TSLP blockade and the efficacy of tezepelumab in severe asthma using data from key trials.

Dual Phosphodiesterase 3 and 4 Inhibitor Ensifentrine Reduces Exacerbation Rate and Risk in Patients With Moderate to Severe COPD

IntroductionExacerbations in chronic obstructive pulmonary disease (COPD) can be life-threatening and lead to irreversible declines in lung function and quality of life. Medications that reduce exacerbation burden are an unmet need, as exacerbations put patients at risk for more exacerbations and decrease quality of life. Ensifentrine is a novel, first-in-class, selective, dual inhibitor of phosphodiesterase 3/4 with demonstrated nonsteroidal anti-inflammatory activity and bronchodilatory effects. Research QuestionDoes ensifentrine reduce the rate and/or risk of COPD exacerbations? Study Design and MethodsA prespecified, pooled analysis of the phase 3 clinical trials ENHANCE-1 (NCT04535986) and ENHANCE-2 (NCT04542057) was conducted to assess the effect of ensifentrine on exacerbation rate and risk (time to first exacerbation). The trials included symptomatic patients aged 40-80 years with moderate-to-severe COPD who received 3 mg twice-daily ensifentrine over 24 weeks or placebo. Subgroup analyses and frequent exacerbator transition risk were conducted post-hoc. ResultsIn total, 975 ensifentrine-treated and 574 placebo-treated patients were included in the pooled analysis, including 62% on concomitant LAMA or LABA therapy and 18% on concomitant inhaled corticosteroid therapy. Ensifentrine was associated with significant reductions in the rate (rate ratio, 0.59; 95% CI, 0.43-0.80; P < 0.001) and risk (hazard ratio, 0.59; 95% CI, 0.44-0.81; P < 0.001) of moderate/severe exacerbations compared with placebo. Reductions in the rate and risk of exacerbations were generally consistent across patient subgroups, including age, sex, race, background maintenance medication use, chronic bronchitis, eosinophil count, COPD severity, and exacerbation history. Ensifentrine was associated with a numerical delay in transitioning from an infrequent exacerbator (GOLD B) to a frequent exacerbator (GOLD E) compared with placebo. ConclusionEnsifentrine reduced the rate of exacerbations and increased the time to first exacerbation among patients with COPD across a broad range of clinically relevant subgroups.

Dupilumab 200 mg was efficacious in children (6-11 years) with moderate-to-severe asthma for up to 2 years: EXCURSION open-label extension study.

The phase 3 VOYAGE (NCT02948959) and open-label extension EXCURSION (NCT03560466) studies evaluated dupilumab in children (6-11 years) with uncontrolled moderate-to-severe asthma. This post hoc analysis assessed the efficacy and safety of add-on dupilumab 200 mg every 2 weeks (q2w), the largest dose cohort in both studies, in children from VOYAGE who participated in EXCURSION. Annualized rate of severe asthma exacerbations (AERs), change in prebronchodilator percent predicted forced expiratory volume in 1 s (ppFEV1), and treatment-emergent adverse events were assessed in children with moderate-to-severe asthma who received dupilumab 200 mg q2w in VOYAGE and EXCURSION (dupilumab/dupilumab arm) and those who received placebo in VOYAGE and dupilumab 200 mg q2w in EXCURSION (placebo/dupilumab arm). These endpoints were also assessed in children with moderate-to-severe type 2 asthma (defined as blood eosinophil count ≥150 cells/µL or FeNO ≥20 ppb at the parent study baseline [PSBL]). In the overall population, dupilumab reduced AER and improved prebronchodilator ppFEV1 in the dupilumab/dupilumab arm (n = 158) for up to 2 years. Children receiving placebo/dupilumab (n = 85) showed similar reductions after initiation of dupilumab 200 mg q2w in EXCURSION. Similar results were observed for children with type 2 asthma at PSBL. The safety profile was consistent with the known safety profile of dupilumab. In children (6-11 years) with uncontrolled moderate-to-severe type 2 asthma, dupilumab 200 mg reduced exacerbation rates and improved lung function for up to 2 years and showed safety consistent with the known dupilumab safety profile.

Patient and clinician preferences for biologic treatments for severe uncontrolled asthma: a discrete choice experiment (DCE)

Objectives To estimate the preferences of patients with asthma and asthma-treating clinicians for attributes of biologic treatments, to compare patients’ and clinicians’ preferences, and to better understand the reasons for their preferences. Methods Adults with moderate-to-severe asthma and clinicians who treat asthma in the US completed a cross-sectional, online survey including a discrete choice experiment (DCE) that consisted of seven attributes spanning treatment efficacy, risk and convenience. Marginal utilities were estimated using a mixed logit model, and relative attribute importance scores calculated. Clinicians were also asked about the value of biomarker agnostic biologic treatments. The survey was followed by qualitative interviews targeting a sub-sample of survey participants, in which the rationale behind their survey responses was discussed. Results In the DCE, both patients and clinicians placed the most importance on exacerbation and hospitalization rate reduction, and risk of injection site reaction. Patients valued location of administration more than clinicians. Rationale for individual-level preferences varied, with patients and clinicians reporting their preference depended on event frequency and anticipated quality of life impacts. Clinicians mentioned compliance and financial impacts, while patients mentioned personal experience, particularly around site reactions. Most patients and clinicians would value a biomarker agnostic asthma treatment. Conclusions Asthma treatment preferences are largely driven by treatment efficacy and minimizing the risk of site reactions, although preferences differ between patients and clinicians across other attributes, highlighting the need for shared decision-making and individualized care.

Advances in inhaler therapy for asthma and chronic obstructive pulmonary disease: a comprehensive review of Fostair™ and Trimbow™.

The management of asthma and chronic obstructive pulmonary disease (COPD) poses considerable challenges due to the intricate nature of these respiratory conditions. Fostair™ and Trimbow™, two pressurized metered dose inhalers, have emerged as noteworthy therapeutic options for treating both asthma and COPD. Fostair combines an inhaled corticosteroid, specifically beclometasone dipropionate, with a long-acting beta2-agonist, formoterol fumarate dihydrate, offering a dual-action approach to mitigate airway inflammation and bronchoconstriction. Conversely, Trimbow integrates a tri-particulate formulation consisting of beclometasone dipropionate, formoterol fumarate dihydrate, and glycopyrronium bromide, providing a comprehensive strategy to target the pathophysiology of COPD and asthma. Recent clinical trials have underscored Trimbow's superior efficacy compared with Fostair, particularly in terms of reducing exacerbation rates and enhancing lung function. However, despite their therapeutic promise, both inhalers encounter challenges, including limited generalizability of study findings and a disparity between in vitro and human trial results. This literature review offers an in-depth analysis of Fostair and Trimbow, delving into their mechanisms of action, clinical applications, and outcomes in human studies for asthma and COPD. Additionally, the review discusses the role of combination therapy in managing respiratory diseases and underscores the necessity for further research to address existing knowledge gaps and optimize therapeutic outcomes.

Real-world biologics response and super-response in the International Severe Asthma Registry cohort.

Biologic asthma therapies reduce exacerbations and long-term oral corticosteroids (LTOCS) use in randomized controlled trials (RCTs); however, there are limited data on outcomes among patients ineligible for RCTs. Hence, we investigated responsiveness to biologics in a real-world population of adults with severe asthma. Adults in the International Severe Asthma Registry (ISAR) with ≥24 weeks of follow-up were grouped into those who did, or did not, initiate biologics (anti-IgE, anti-IL5/IL5R, anti-IL4/13). Treatment responses were examined across four domains: forced expiratory volume in 1 second (FEV1) increase by ≥100 mL, improved asthma control, annualized exacerbation rate (AER) reduction ≥50%, and any LTOCS dose reduction. Super-response criteria were: FEV1 increase by ≥500 mL, new well-controlled asthma, no exacerbations, and LTOCS cessation or tapering to ≤5 mg/day. 5.3% of ISAR patients met basic RCT inclusion criteria; 2116/8451 started biologics. Biologic initiators had worse baseline impairment than non-initiators, despite having similar biomarker levels. Half or more of initiators had treatment responses: 59% AER reduction, 54% FEV1 increase, 49% improved control, 49% reduced LTOCS, of which 32%, 19%, 30%, and 39%, respectively, were super-responses. Responses/super-responses were more frequent in biologic initiators than in non-initiators; nevertheless, ~40-50% of initiators did not meet response criteria. Most patients with severe asthma are ineligible for RCTs of biologic therapies. Biologics are initiated in patients who have worse baseline impairments than non-initiators despite similar biomarker levels. Although biologic initiators exhibited clinical responses and super-responses in all outcome domains, 40-50% did not meet the response criteria.

Outcomes of patients with COPD switching from multiple-inhaler to once-daily single-inhaler triple therapy in a real-world primary care setting in England: a retrospective pre-post cohort study

BackgroundCompared with multiple-inhaler triple therapy (MITT), single-inhaler triple therapy (SITT) with fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) demonstrated improved lung function and meaningful improvements in chronic obstructive pulmonary disease (COPD) Assessment Test score....

Exploring Definitions and Predictors of Response to Biologics for Severe Asthma

Biologic effectiveness is often assessed as response, a term that eludes consistent definition. Identifying those most likely to respond in real-life has proven challenging. To explore definitions of biologic responders in adults with severe asthma and investigate patient characteristics associated with biologic response. This was a longitudinal cohort study using data from 21 countries, which shared data with the International Severe Asthma Registry. Changes in four asthma outcome domains were assessed in the 1-year period before and after biologic initiation in patients with a predefined level of prebiologic impairment. Responder cutoffs were 50% or greater reduction in exacerbation rate, 50% or greater reduction in long-term oral corticosteroid daily dose, improvement in one or more category in asthma control, and 100 mL or greater improvement in FEV1. Responders were defined using single and multiple domains. The association between prebiologic characteristics and postbiologic initiation response was examined by multivariable analysis. A total of 2,210 patients were included. Responder rate ranged from 80.7% (n= 566 of 701) for exacerbation response to 10.6% (n= 9 of 85) for a four-domain response. Many responders still exhibited significant impairment after biologic initiation: 46.7% (n= 206 of 441) of asthma control responders with uncontrolled asthma before the biologic still had incompletely controlled disease postbiologic initiation. Predictors of response were outcome-dependent. Lung function responders were more likely to have higher prebiologic FeNO (odds ratio= 1.20 for every 25-parts per billion increase), and shorter asthma duration (odds ratio= 0.81 for every 10-year increase in duration). Higher blood eosinophil count and the presence of type 2-related comorbidities were positively associated with higher odds of meeting long-term oral corticosteroid, control, and lung function responder criteria. Our findings underscore the multimodal nature of response, showing that many responders experience residual symptoms after biologic initiation and that predictors of response vary according to the outcome assessed.

Long-term therapy with CFTR modulators consistently improves glucose metabolism in adolescents and adults with cystic fibrosis

BackgroundImpaired glycemic control and the subsequent development of Cystic fibrosis Related Diabetes (CFRD) are prevalent complications, affecting up to 50 % of adults with cystic fibrosis (CF). CFTR modulator (CFTRm) therapies improve pulmonary functions, reduce exacerbation rates, increase survival in people with CF (pwCF) and appear to have a positive effect on extrapulmonary manifestations, such as nutritional state, improvements in upper respiratory symptoms, and quality of life. Initial findings indicate that CFTRm may have a positive impact on short-term glycemic control; however, long-term effects remain uncertain at present. MethodsIn this retrospective study, data were collected and analyzed on 15 pwCF, ages 13–37 years, started on CFTRm therapy. Oral Glucose Tolerance Test (OGTT) results were compared pre- and post-CFTRm therapy. ResultsThe 120-min OGTT value decreased from 159.7 mg/dL to 130.4 mg/dL post-CFTRm (p = 0.047). The average time elapsed between the two OGTTs was 49.87 months (ranging 9–157 months, median 38 months). Glycemic status improved in six pwCF (two CFRD to normal (NGT)/indeterminate (INDET) glucose tolerance; two impaired glucose tolerance (IGT) to INDET; two INDET to NGT) and worsened in one (IGT to CFRD). Six pwCF and NGT remained stable with no changes in glycemic status throughout the follow-up period. ConclusionsCFTRm therapy may decelerate the glycemic control deterioration in pwCF over an extended period. These findings indicate the need for periodic OGTTs following the initiation of CFTRm therapy to appropriately adjust insulin requirements and prevent hypoglycemia. Further larger cohorts are required to authenticate and substantiate these findings.

Ratio of plasma IL-13/TNF- ∝ and CXCL10/CCL17 predicts mepolizumab and omalizumab response in asthma better than eosinophil count or immunoglobulin E level

To date, most studies to identify biomarkers associated with response to the anti-interleukin 5 agent, mepolizumab, and to the anti-immunoglobulin E agent, omalizumab have focused on clinically available biomarkers, such as the peripheral blood eosinophil counts (BEC) and total immunoglobulin E (IgE). However, these biomarkers often have low predictive accuracy, with many patients with eosinophilic or allergic asthma failing to demonstrate clinical response to mepolizumab or omalizumab respectively. In this study, we evaluated the association of baseline pre-biologic plasma levels of 26 cytokines and chemokines, including T-helper 1 (Th1)-, Th2-, Th17-related cytokines, and their ratios with subsequent clinical response to mepolizumab or omalizumab. We defined clinical response as a reduction in the baseline annual exacerbation rate by half or more over the one-year period following initiation of the biologic. Baseline levels of plasma IL-13 were differentially elevated in responders versus non-responders to mepolizumab and plasma CXCL10 levels were differentially elevated in responders to omalizumab. The ratio of IL-13/TNF-α had the best sensitivity and specificity in predicting response to mepolizumab and CXCL10/CCL17 to omalizumab, and these performed better as predictive biomarkers of response than BEC and IgE. Cytokines and chemokines associated with airway eosinophilia, allergic inflammation, or Th2 inflammation, such as IL-13 and CXCL10, may be better predictors of clinical response to mepolizumab and omalizumab, than IL-5 or IgE, the targets of mepolizumab and omalizumab.

Mixed-methods evaluation of an enhanced asthma biologics clinical pathway in the West Midlands UK.

Biologic treatments can alleviate severe asthma symptoms and reduce health service use. However, service capacity limits and low referral rates from primary care indicate unmet patient need. We report a mixed-methods evaluation of an enhanced severe asthma pathway implemented in Staffordshire and Stoke-on-Trent, UK which aimed to optimise primary care referrals through training/education, and increased capacity in specialist clinics. Quantitative analysis assessed patient wait times between pathway stages, prescribing changes, exacerbations, hospital admissions and asthma control. Interviews with 12 stakeholders evaluated perceptions of the enhanced pathway across settings. In 12 months, 564 patients from 28 general practices were reviewed for biologics eligibility, of whom 125 (22.2%) were referred for specialist assessment. Wait times were significantly lower under the enhanced pathway when compared against historic patients following the standard pathway, and reduced overall from a mean of 76.4 to 26.7 weeks between referral and biologics initiation (p < 0.001). Patients commencing biologics (n = 46) showed significantly reduced reliever inhaler prescribing rates (p = 0.037), 60% lower oral steroid use (p < 0.001), significantly reduced exacerbation rates (p < 0.001) and fewer hospital admissions (p < 0.001) compared with the 12 months pre-treatment. Mean asthma control scores reduced from 3.13 pre-initiation to 1.89 post-initiation (p < 0.001) - a clinically significant improvement. Interviewees viewed the enhanced pathway positively, although ongoing issues related to difficulties engaging primary care amid concerns around increased workloads and pathway capacity. The large number of referrals generated from a comparatively small number of general practices confirms substantial unmet need that an enhanced severe asthma pathway could help address if implemented routinely.

Blood eosinophils and fractional exhaled nitric oxide are prognostic and predictive biomarkers in childhood asthma

Blood eosinophils and fractional exhaled nitric oxide (Feno) are prognostic biomarkers for exacerbations and predict lung function responses to dupilumab in adolescents and adults with asthma. We evaluated the relationship between baseline blood eosinophils and Feno and response to dupilumab in children with asthma. Children aged 6 to 11 years with uncontrolled moderate-to-severe asthma (n= 408) were randomized to receive dupilumab 100/200 mg by body weight or volume-matched placebo every 2 weeks for 52 weeks. Annualized exacerbation rate (AER) reduction and least squares mean change in prebronchodilator percent predicted forced expiratory volume in 1 second (ppFEV1) at week 12 were assessed according to cutoff baseline levels for Feno (<20 ppb vs ≥20 ppb) and blood eosinophil count (<150, ≥150 to <300, ≥300 to <500, and ≥500 cells/μL). Quadrant analyses in populations defined by biomarker thresholds and spline models across continuous end points assessed the relationship with Feno and eosinophil count. Interaction testing evaluated the independent roles of Feno and blood eosinophils as predictive markers. Exacerbation risk and magnitude of AER reduction increased in subgroups with higher baseline biomarker levels. Quadrant analyses revealed that disease of patients with either elevated Feno or eosinophil counts demonstrated a clinical response to dupilumab. Interaction testing indicated blood eosinophil counts or Feno independently added value as predictive biomarkers. In children with uncontrolled moderate-to-severe asthma, blood eosinophil counts and Feno are clinically relevant biomarkers to identify those at risk for asthma exacerbations, as well as those with disease with clinical response to dupilumab. Liberty Asthma VOYAGE ClinicalTrials.gov NCT02948959.

Biological Anti-IL-5/IL-5R Therapeutics for Chronic Obstructive Pulmonary Disease (COPD) with Specific Treatable Traits: A Real-World Retrospective Analysis.

We describe the use of anti-IL-5 monoclonal antibodies from a COPD clinic, a source other than traditional clinical trials. The objectives were to characterize the patient subgroup prescribed anti-IL-5 monoclonal antibodies and to report potential benefits. This is a retrospective case series study of 17 patients treated in a COPD subspecialty clinic. All patients had a diagnosis of COPD (post-bronchodilator FEV1/FVC <0.7) and had been prescribed an anti-IL-5 biologic for at least 8 months. Acute exacerbations of COPD (AECOPDs) were collected as reported in electronic medical records. All patients (17) enrolled were treated with biologics for ≥8 months, and 13 (76%) for ≥1 year. Patients were characterized by severe disease traits, FEV1 <50% predicted, recurrent exacerbations (3.5 moderate-to-severe AECOPDs in the year before treatment), high peripheral blood eosinophil counts (≥250 cells/μL in the previous year), all on inhaled triple therapy, and only 1 patient with a diagnosis of asthma prior to smoking. There was a statistically significant decrease in the exacerbation rate compared with baseline after 8 and 12 months of anti-IL-5 treatment, respectively, yielding the equivalent of a 2-3x reduction in exacerbation rate. Absolute FEV1 decreased, and the decline in FEV1 % of predicted reached statistical significance (p<0.05); CAT score improved (p<0.05). This real-world evidence data aligns with existing studies suggesting the potential benefit of anti-IL-5 treatment for specific patients with COPD and therefore advocates for further investigation of RCTs on the use of anti-IL-5 biologics for well-characterized patients with COPD.

Bronchial thermoplasty for severe asthma: potential mechanisms and response markers.

Severe asthma (SA) poses a significant challenge to management and treatment, leading to a reduced quality of life and a heavy burden on society and healthcare resources. Bronchial thermoplasty (BT) has emerged as a non-pharmacological intervention for SA, demonstrating its efficacy and safety in improving patients' quality of life and reducing exacerbation rates for over a decade. In particular, BT encounters various obstacles in its clinical application. Since asthma is characterized by high heterogeneity, not all patients derive effective outcomes from BT. Furthermore, current knowledge of markers that indicate response to BT remains limited. Recent research has shed light on the intricate mechanism of action of BT, which extends beyond simple smooth muscle ablation. Therefore, to enhance the clinical practice and implementation of BT, this paper aims to elucidate the mechanism of action and identify potential markers associated with BT response.

The ADEM project: implementation of ‘Good medicines use conversation’ for COPD-patients, embedded in multidisciplinary context.

COPD is a chronic, progressive disease, for which a multidisciplinary approach is crucial. Appropriate follow-up is crucial to improve the quality of life of COPD-patients and reduce associated healthcare costs. &#x0D; A ‘Good medicines use conversation’ COPD is a pharmaceutical care intervention, conducted by the community pharmacist, consisting of a tailored-made education of the COPD-patient on the disease and its treatment. Scientific research (PHARMACOP-trial) has shown that this intervention significantly improves therapy adherence and inhalation technique and reduces exacerbation rates and associated hospitalizations. &#x0D; The aim of the ADEM implementation project was to investigate the needs for a sustainable implementation of this intervention.&#x0D; The ADEM project was conducted in Flemish-Brabant (Belgium), with the integrated care region ‘Leuven Cares’ as a separate entity. &#x0D; All participating pharmacies (9 in region Flemish-Brabant and 8 in region ‘Leuven Cares’) received a support package consisting of: 1) a three-part online training about COPD and a visual COPD-atlas; 2) a population management-tool (a query to identify COPD-patients in the pharmacy, resulting in a list of COPD-patients with a ‘score’ per patient as an initial proxy for patient prioritization); and 3) local interdisciplinary meetings (LIM) to discuss and promote the intervention. Pharmacist of the region Caring Leuven additionally received individual care plans, providing an overview of the healthcare status of each COPD-patient, and an individual coaching session.&#x0D; Semi-structured interviews were conducted with 8 participating pharmacists (4 region Flemish-Brabant, 4 region ‘Leuven Cares’). Thematic analysis was performed.&#x0D; &#x0D; All elements of the support package were positively evaluated by the participating pharmacists. The population management tool seemed to support pharmacists in planning, interpreting and prioritizing care for COPD-patients. A follow-up study is needed to further investigate the tool and to what extent population management contributes to a more qualitative and effective pharmaceutical care. &#x0D; COVID-19, lack of personnel, lack of reimbursement and lack of time were identified as limiting factors for the implementation of the protocol-based COPD-intervention. Cooperation with the GP was indicated by the majority as minimal and insufficient. Therefore, LIM’s were evaluated as very important to inform GP’s about the pharmaceutical intervention and make local agreements about the multidisciplinary approach of COPD.&#x0D; The findings of this study are in line with the available evidence on the implementation of new services in pharmacies. Many pharmacists have the intrinsic motivation to offer extended pharmaceutical care, but current practices often do not allow this. Population management appeared to be a major factor that can be used to facilitate the implementation. By considering the needs of the local population, pharmacists can work in a more targeted way and prioritize the pharmaceutical services they offer. Given the group of chronically ill people in Belgium is expected to grow in the coming years due to the increasing ageing of the population, there will be an increasing demand for specialized interventions and advice from the pharmacist. It is therefore necessary to provide a sufficient framework for these services, bearing in mind the needs of the local population and the requirement for a pragmatic approach in the pharmacy. &#x0D;

Efficacy and Safety of Mepolizumab in the Management of Severe Eosinophilic Asthma: A Systematic Review.

Severe eosinophilic asthma (SEA) is characterized by persistent airway inflammation and frequent exacerbations despite standard treatments. Mepolizumab, a monoclonal antibody that reduces eosinophil levels by targeting interleukin-5, has emerged as an add-on therapy for patients with SEA. This systematic review evaluated mepolizumab's efficacy and safety for treating SEA. A comprehensive literature search was conducted across major databases. Thirty-two studies with over 6,000 patients were included, comprising randomized controlled trials, open-label extensions, and real-world observational analyses. Study quality and risk of bias were assessed using standard tools. Meta-analysis was deemed inappropriate due to heterogeneity. Instead, a narrative synthesis was performed. Mepolizumab significantly reduced exacerbation rates by around 50% and improved symptoms and lung function compared to placebo in pivotal trials. Long-term open-label studies showed sustained reductions in exacerbations and stable lung function for up to 4.5 years. Real-world data demonstrated consistent 50%-90% exacerbation decreases across diverse patient populations over 6-24 months. Mepolizumab exhibited an acceptable safety profile, with mild injection site reactions and headaches as most common adverse events. While specific subgroups may show enhanced responses, mepolizumab displayed broad efficacy regardless of patient demographics or phenotypes. The extensive evidence provides robust support for mepolizumab as an efficacious and safe add-on treatment option for patients with severe, refractory eosinophilic asthma. Further high-quality comparative effectiveness research is warranted to optimize patient selection and positioning among emerging biologics.

Efficacy of dupilumab in patients with uncontrolled, moderate-to-severe asthma with fungal sensitization.

Fungal sensitization (FS) exacerbates asthma in patients who have elevated type 2 inflammatory response. Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for interleukin (IL)-4 and IL-13, key and central drivers of type 2 inflammation in multiple diseases. This post hoc analysis, funded by the manufacturers of dupilumab, was conducted to assess dupilumab efficacy in patients from the phase 3 LIBERTY ASTHMA QUEST trial (NCT02414854) and TRAVERSE open-label extension (NCT02134028) study who had uncontrolled, moderate-to-severe asthma with type 2 inflammatory phenotype (defined as blood eosinophil count ≥150 cells/μL or FeNO ≥25 ppb) and with FS (defined as IgE specific to Alternaria alternata, Aspergillus fumigatus or Cladosporium herbarum >0.35 IU/mL). We evaluated annualized rate of severe exacerbations (AER), change from baseline in pre-bronchodilator (BD) forced expiratory volume in 1 s (FEV1 ), asthma control (per 5-item Asthma Control Questionnaire [ACQ-5]) and biomarker levels (blood eosinophil count, fractional exhaled nitric oxide [FeNO], total IgE, fungal-specific IgEs, thymus and activation-regulated chemokine [TARC] and eotaxin-3). Dupilumab vs. placebo reduced AER, improved pre-BD FEV1 and asthma control (ACQ-5), and reduced serum IgE levels, blood eosinophil count, TARC, eotaxin-3 and FeNO in patients both with and without FS after 52 weeks of treatment in QUEST. Reductions in asthma exacerbation rates and improvements in all other variables were sustained over the TRAVERSE open-label extension study. Dupilumab demonstrated efficacy during prolonged treatment in patients with uncontrolled, moderate-to-severe asthma with FS.