Therapy For Severe Asthma Research Articles

The Influence of Emphysema on Treatment Response to Biologic Therapy in Severe Asthma.

Patients with severe asthma (SA) benefit from biologic therapy substantially. However, the impact of smoking-related comorbidities remains unclear due to the exclusion of patients with ≥10 pack-years from asthma studies. Our aim was to examine the effects of emphysema on biologic treatment response in SA in this retrospective cohort study. Pulmonary emphysema was examined using computed tomography. Patients with SA were included and divided into two groups based on emphysema quantity (≥5% or <5%). They received either anti-IgE (22.1%), anti-IL-5-(receptor) (52.3%), or anti-IL-4/IL-13 (25.6%) biologic therapy. Treatment response was assessed after 7.8 ± 2.5 months based on acute exacerbations (AE), oral corticosteroid (OCS) therapy, Asthma Control Test (ACT), forced expiratory volume in 1 second (FEV1) and using the Biologics Asthma Response Score (BARS). This study comprised 86 patients (mean age 56.1 ± 12.8 years; 54% female). Half (43, 50.0%) were never-smokers, half ex-smokers with an average of 26.9 ± 18.2 pack-years. Patients with ≥5% emphysema were more often ex-smokers (80% vs 41%, p=0.002), had poorer lung function (FEV1 median 1.3 [interquartile range: 1.0;1.6] vs 1.8[1-2;2.4] L, p=0.037), and more comorbid COPD (50% vs 21%, p=0.012). However, no significant differences were noted in treatment response regarding annualized AE rate (-2.5[-5;-1] vs -3.0[-5;-2] n/year, p=0.295) and OCS reduction (-4[-10;0] vs -5[-10;0] mg, p=0.691), ACT score (5[3;9] vs 4[0;9] points, p=0.579) or FEV1 improvement (0.03[-0.15;0.25] vs 0.23[-0.5;0.49] L, p=0.052), BARS (p=0.312), and remission rates (15.0% vs 19.7%, p=0.753). In patients with severe asthma, those with comorbid emphysema show similar treatment response to biologic therapy. Therefore, suitable patients should not be denied biologics due to the presence of emphysema.

Real-World Efficacy of Biological Therapies in Severe Asthma: A Focus on Small Airways.

Background: Severe asthma is a challenging condition that often resists traditional treatments and requires high-dose inhaled corticosteroids and other controllers to manage uncontrolled symptoms. Recent advances include the use of biologic agents targeting specific inflammation pathways, which have improved symptom control and quality of life, although their effects on small airways remain less understood. Methods: This prospective observational study, conducted at Tor Vergata University Hospital in Rome from July 2021 to March 2024, aims to evaluate the efficacy of treatments in patients with uncontrolled severe asthma. It involves baseline assessments and follow-ups at 1 and 3 months post-biological therapy initiation, focusing on both spirometric and non-spirometric (oscillometry) measurements of the small airways to provide a comprehensive evaluation of respiratory function. Results: This study, conducted from July 2021 to March 2024, enrolled 40 patients with severe asthma, ultimately analyzing data from 31 participants who underwent biological therapy. The results showed significant improvements in asthma symptoms, the ACT scores increased significantly from visit 1 to visit 2 (p = 0.00008) and from visit 1 to visit 3 (p = 0.00047), and pulmonary function tests, with notable increases in FEV1 (from visit 1 (74.97 ± 23.43%) to visit 2 (82.96 ± 26.57%, p = 0.041) and to visit 3 (88.89 ± 31.41%, p = 0.003)) and quality of life scores, and substantial reductions in specific airway resistance and small airway dysfunction markers (the PEF, %pr post-BD showed significant improvement from visit 1 to visit 3 (p = 0.012)). However, oscillometric measurements showed no significant changes post-therapy. Conclusions: The study concluded that there was an improvement in the small airways measured by non-oscillometric values, without significant improvements in oscillometric parameters. Additionally, a significant improvement in symptoms was observed after the first month of therapy. There was also a significant increase in respiratory function after one to three months of therapy.

Revealing the gap: fractional exhaled nitric oxide and clinical responsiveness to biological therapy in severe asthma - a retrospective study.

A proportion of patients with severe asthma treated with biological drugs undergoes a significant decline in F ENO. However, variations in F ENO are largely independent of the clinical efficacy of the biological drug therapy. https://bit.ly/3xWszYJ.

Association of Obesity and Severe Asthma in Adults.

The incidence of obesity and asthma continues to enhance, significantly impacting global public health. Adipose tissue is an organ that secretes hormones and cytokines, causes meta-inflammation, and contributes to the intensification of bronchial hyperreactivity, oxidative stress, and consequently affects the different phenotypes of asthma in obese people. As body weight increases, the risk of severe asthma increases, as well as more frequent exacerbations requiring the use of glucocorticoids and hospitalization, which consequently leads to a deterioration of the quality of life. This review discusses the relationship between obesity and severe asthma, the underlying molecular mechanisms, changes in respiratory function tests in obese people, its impact on the occurrence of comorbidities, and consequently, a different response to conventional asthma treatment. The article also reviews research on possible future therapies for severe asthma. The manuscript is a narrative review of clinical trials in severe asthma and comorbid obesity. The articles were found in the PubMed database using the keywords asthma and obesity. Studies on severe asthma were then selected for inclusion in the article. The sections: 'The classification connected with asthma and obesity', 'Obesity-related changes in pulmonary functional tests', and 'Obesity and inflammation', include studies on subjects without asthma or non-severe asthma, which, according to the authors, familiarize the reader with the pathophysiology of obesity-related asthma.

Clinical and allergological characteristics of patients with severe bronchial asthma in the regional registry and phenotyping principles for the targeted therapy choice

Introduction. Severe asthma targeted therapy effectiveness depends on precise targeting of the selected drug to the key link in pathogenesis. Therefore, severe asthma phenotyping in real clinical practice is relevant.Aim. To determine main clinical and allergological characteristics of patients with severe asthma and to establish important phenotyping signs determined choice of a targeted drug for severe asthma treatment.Materials and methods. The prospective and retrospective study involved patients (n = 198) of the Sverdlovsk region registry receiving targeted therapy of severe asthma. Considering clinical and allergological picture, allergic, non-allergic eosinophilic and mixed severe asthma phenotypes were identified. Clinical and laboratory characteristics of phenotypes were described. A phenotyping algorithm was developed.Results. In the register of patients (n = 198) with severe asthma, non-allergic eosinophilic asthma was 46.5%, allergic – 34.8%, mixed – 18.7%. Significant signs for phenotyping were identified: age of asthma onset, proven allergy, Phadiatop ImmunoCAP level and blood eosinophils on baseline, concomitant allergic rhinitis, chronic rhinosinusitis with nasal polyps and hyper-sensitivity to NSAIDs. The main signs of allergic severe asthma determined: early onset, proven allergy and a positive result of Phadiatop ImmunoCAP (the probability of allergic phenotype increases with Phadiatop ≥ 1.53 PAU/l). Signs of non-allergic eosinophilic asthma were eosinophilia ≥ 150 cells/µl, absence of allergy, concomitant chronic rhinosinusitis with nasal polyps and hypersensitivity to NSAIDs, late onset (after 30 years). Signs were identified for mixed asthma: presence of proven allergy or latent sensitization in combination with high level of Phadiatop ImmunoCAP, late onset, eosinophilia ≥ 300 cells/µl, chronic rhinosinusitis with nasal polyps, hypersensitivity NSAIDs.Conclusions. The algorithm for severe asthma phenotyping based on the isolation of eosinophilia of allergic and non-allergic origin is proposed. Severe asthma phenotyping, which can be carried out in real clinical practice, should facilitate the selection of an initial targeted drug.

Biologic therapies for severe asthma with persistent type 2 inflammation.

Asthma is a chronic inflammatory airways disease with reversible airflow obstruction, characterised in the majority by type 2 airway inflammation. Type 2 inflammation results in secretion of interleukin-4, -5 and -13 in the airways, recruitment of inflammatory cells (especially eosinophils and mast cells), and airway changes such as mucus hypersecretion and increased airway reactivity. Approximately 5 to 10% of people with asthma, despite optimal therapy and adherence to treatment with inhaled corticosteroids and long-acting beta2 agonists, are unable to obtain good symptom control and continue to experience exacerbations requiring oral corticosteroids; this is known as 'severe asthma'. In many cases, this is associated with persistent type 2 inflammation, indicated by the persistent elevation of blood eosinophils or fractional exhaled nitric oxide. In people with severe asthma and persistent type 2 inflammation, biologic (monoclonal antibody) therapy is indicated. Biologic therapies currently available in Australia for asthma are benralizumab, dupilumab, mepolizumab and omalizumab. They are administered subcutaneously and are generally well tolerated. Biologic asthma therapies are very effective in improving symptoms, and reducing the rate of exacerbations and use of oral corticosteroids, in people with severe asthma and persistent type 2 inflammation. Inhaled corticosteroid treatment should be continued in people using a biologic therapy.

Effectiveness and safety of biological therapy in patients with severe asthma in a real clinical practice

To assess effectiveness and safety of biological therapy in patients with severe asthma during 5 yr follow-up. We recruited 129 adult outpatients (29% males) aged 18-81 yrs with severe asthma were followed up during 5 yrs and were examined for every 3-6 months. Eighty five patients were treated by conventional therapy (ICS/LABA ± tiotropium, montelukast, OCS) only and 44 pts additionally received biologicals (оmalizumab - 9 pts, мepolizumab - 8 pts, benralizumab - 11 pts, dupilumab - 16 pts). Pulmonary function tests were measured by dry spirometer (2120, Vitalograph Ltd., UK). Eosinophil count in blood was assessed by automatic haemoanalyser. Fraction of exhaled nitric oxide was measured by a chemiluminescence analyzer (LR4100; Logan Research, UK). Asthma control and quality of life were assessed by using Russian versions of ACQ-5 and SGRQ. The use of biologicals led to a more significant reduction of exacerbations and OCS use, improvement of lung function, asthma control and quality of life, decrease of eosinophil and fraction of exhaled nitric oxide than conventional therapy of severe asthma (p<0.05). Systemic side effects were not registered, frequency of local adverse reactions (edema, hyperemia and itching at injection site) was 14%. Long-term use of biologicals added to conventional therapy in patients with severe asthma is characterized by high effectiveness and favorable safety profile.

Bronchial Thermoplasty: An Unutilized Therapy for Severe Asthma Between Caution and Prospects

Bronchial Thermoplasty: An Unutilized Therapy for Severe Asthma Between Caution and Prospects

Tezepelumab: patient selection and place in therapy in severe asthma.

Asthma is a disease characterised by heterogeneous and multifaceted airway inflammation. Despite the availability of effective treatments, a substantial percentage of patients with the type 2 (T2)-high, but mainly the T2-low, phenotype complain of persistent symptoms, airflow limitation, and poor response to treatments. Currently available biologicals target T2 cytokines, but no monoclonal antibodies or other specific therapeutic options are available for non-T2 asthma. However, targeted therapy against alarmins is radically changing this perspective. The development of alarmin-targeted therapies, of which tezepelumab (TZP) is the first example, may offer broad action on inflammatory pathways as well as an enhanced therapeutic effect on epithelial dysfunction. In this regard, TZP demonstrated positive results not only in patients with severe T2 asthma but also those with non-allergic, non-eosinophilic disease. Therefore, it is necessary to identify clinical features of patients who can benefit from an upstream targeted therapy such as anti-thymic stromal lymphopoietin. The aims of this narrative review are to understand the role of alarmins in asthma pathogenesis and epithelial dysfunction, examine the rationale underlying the indication of TZP treatment in severe asthma, summarise the results of clinical studies, and recognise the specific characteristics of patients potentially eligible for TZP treatment.

Long-term multicenter comparison shows equivalent efficacy of monoclonal antibodies in severe asthma therapy

BackgroundMonoclonal antibodies (biologics) drastically changed severe asthma therapy. Mepolizumab (anti-interleukin (IL) 5), benralizumab (anti-IL5 receptor alpha), and dupilumab (anti-IL4/13) are the most used biologics in this context. While all biologics are efficient individually, the choice of biologic is complicated by insufficient data on their comparative long-term treatment efficacy. Here, we compare the real-life efficacy of these biologics in asthma therapy over 12 months.Methods280 severe asthma patients treated with mepolizumab (129/280, 46%), benralizumab (83/280, 30%) or dupilumab (68/280, 24%) for one year were analyzed retrospectively. Data were collected at baseline and after 6 and 12 months of therapy. Endpoints were changes pulmonary function (PF), exacerbation rate, oral corticosteroid (OCS) use and dose, asthma control test (ACT) score and fractional exhaled nitric oxide (FeNO) levels as well as responder status measured by the recently published “Biologic Asthma Response Score” (BARS).ResultsAll biologics led to significant improvements in PF, ACT and OCS dose. Only Mepolizumab and Benralizumab significantly decreased the exacerbation rate, while only Mepolizumab and Dupilumab significantly decreased FeNO. Responder rates measured by BARS were high across all groups: roughly half of all patients achieved full response and most of the remainder achieved at least partial responder status. Overall, outcomes were similar between groups after both 6 and 12 months.ConclusionsAll biologics showed great efficacy in individual parameters and high responder rates measured by BARS without a clinically relevant advantage for any antibody. Response was usually achieved after 6 months and retained at 12 months, emphasizing the utility of early response assessment.

Safety of Biological Therapies for Severe Asthma: An Analysis of Suspected Adverse Reactions Reported in the WHO Pharmacovigilance Database.

The management of uncontrolled severe asthma has greatly improved since the advent of novel biologic therapies. Up to August 2022, five biologics have been approved for the type 2 asthma phenotype: anti-IgE (omalizumab), anti-IL5 (mepolizumab, reslizumab, benralizumab), and anti-IL4 (dupilumab) monoclonal antibodies. These drugs are usually well tolerated, although long-term safety information is limited, and some adverse events have not yet been fully characterized. Spontaneous reporting systems represent the cornerstone for the detection of potential signals and evaluation of the real-world safety of all marketed drugs. The aim of this study was to provide an overview of safety data of biologics for severe asthma using VigiBase, the World Health Organization global pharmacovigilance database. We selected all de-duplicated individual case safety reports (ICSRs) attributed to five approved biologics for severe asthma in VigiBase, up to 31st August 2022 (omalizumab, mepolizumab, reslizumab, benralizumab and dupilumab). Descriptive frequency analyses of ICSRs were carried out both as a whole class and as individual products. Reporting odds ratios (ROR) with 95% confidence intervals (CIs) were used as the measure of disproportionality for suspected adverse drug reactions (ADRs) associated with the study drugs compared with either all other suspected drugs (Reference Group 1, RG1) or inhaled corticosteroids plus long-acting β-agonists (ICSs/LABAs) (Reference Group 2, RG2) or with oral corticosteroids (OCSs) (Reference Group 3, RG3). Overall, 31,724,381 ICSRs were identified in VigiBase and 167,282 (0.5%) were related to study drugs; the remaining reports were considered as RG1. Stratifying all biologic-related ICSRs by therapeutic indication, around 29.4% (n = 48,440) concerned asthma use; omalizumab was mainly indicated as the suspected drug (n = 20,501), followed by dupilumab, mepolizumab, benralizumab and reslizumab. Most asthma ICSRs concerned adults (57%) and women (64.1%). Asthma biologics showed a higher frequency of serious suspected ADR reporting than RG1 (41.3% vs 32.3%). The most reported suspected ADRs included asthma, dyspnea, product use issue, drug ineffective, cough, headache, fatigue and wheezing. Asthma biologics were disproportionally associated with several unknown or less documented adverse events, such as malignancies, pulmonary embolism and deep vein thrombosis with omalizumab; alopecia and lichen planus with dupilumab; alopecia and herpes infections with mepolizumab; alopecia, herpes zoster and eosinophilic granulomatosis with polyangiitis related to benralizumab; and alopecia with reslizumab. The most frequently reported suspected ADRs of asthma biologics in VigiBase confirmed the presence of well-known adverse effects such as general disorders, injection-site reactions, nasopharyngitis, headache and hypersensitivity, while some others (e.g. asthma reactivation or therapeutic failure) could be ascribed to the indication of use. Moreover, the analysis of signals of disproportionate reporting suggests the presence of malignancies, effects on the cardiovascular system, alopecia and autoimmune conditions, requiring further assessment and investigation.

Gut Mycobiome and Asthma.

This review explores the 'gut-lung axis' in asthma with a focus on commensal fungal organisms. We explore how changes to the intestinal commensal fungal community composition alter lung immune function. We comprehensively review available studies that have profiled the composition of the gut mycobiome in adults and children with asthma, and discuss mechanisms of gut-lung interactions that have been described in animal models of asthma. Studies indicate that intestinal fungal dysbiosis, such as an increased abundance of certain fungi like Candida, can elevate the risk of asthma in children and exacerbate it in adults. This effect is mediated through various pathways: the host immune system's sensing of dysbiosis via C-type lectin receptors (e.g., Dectin-2), the impact of pro-inflammatory fungal metabolites (e.g., 12,13-diHOME, prostaglandin E2), and the role of lung immune cells (e.g., group 2 innate lymphoid cells [ILC2], M2 macrophages). We also describe strategies for modulating the gut mycobiome as potential therapies for severe asthma. The review concludes by emphasizing the necessity for further research into the role of the gut mycobiome in asthma to deepen our understanding of these complex interactions.

Exploring Perceptions of Biologic Therapies: A Qualitative Study Among Canadians Living with Severe Asthma.

Biologic therapies have demonstrated benefits for individuals with severe asthma, including reduced daily symptoms and severe exacerbations. However, data describing patient perspectives on these treatments are limited. This study sought to understand the preferences and priorities of Canadians with severe asthma in the context of novel biologic treatment options. Semi-structured, qualitative interviews were conducted among Canadians with severe asthma from July to August 2022. Purposeful sampling included individuals with and without biologic therapy experience. All participants described daily life with severe asthma, experiences and priorities related to asthma treatment and their impressions of biologics. Reflexive thematic analysis was used to explore patterns in the data. Among 18 individuals included, 10 were currently taking or had prior experience with biologic treatment for asthma. Those who had never been treated with biologics were unfamiliar with them, considering treatment, or believed that they may not be eligible. Four themes were developed to convey the perspectives of participants on biologics: (1) life-changing benefits, but not for all; (2) navigating barriers to being prescribed and remaining adherent to biologic treatments; (3) treatment administration preferences are not only about convenience; (4) concerns about safety and the unknown as a source of treatment hesitancy. Findings suggest that the clinical benefits of biologics align with patient perceptions of achieving good asthma control. However, treatment gaps persist among individuals who do not experience a meaningful improvement in their asthma symptoms and those who face barriers accessing biologics. People with severe asthma attributed importance to greater availability of at-home treatment options, improved access to financial support to cover treatment costs and support to address safety concerns. This research provides insight into patient-based treatment priorities and preferences for biologics, which may help inform decision-making related to emerging therapies for severe asthma.

Targeted Therapy for Severe Asthma: Switching Biological agents in Real Clinical Practice — Causes and Consequences

BACKGROUND: The complexity of choosing a genetically engineered biological drug for the treatment of severe bronchial asthma is due to the intersection of disease endotypes and phenotypes. Mistakes in biological choice lead to the discontinuation and/or switching of the drug because of insufficient effectiveness of therapy.&#x0D; AIM: To determine the reasons for stopping targeted therapy and biological switching effectiveness in patients with severe bronchial asthma in clinical practice.&#x0D; MATERIALS AND METHODS: Patients with severe bronchial asthma (n=116) from the Sverdlovsk region register were divided into three groups: (1) continuous, (2) stoppers, and (3) switchers. Predictors of biological withdrawal and switching, reasons for the first biological stopping, switching schemes, therapy effectiveness after switching according to the asthma control test (ACT), asthma quality of life questionnaire (AQLQ), 22-item sinonasal outcome test [SNOT-22], forced expiratory volume in the first second, need for systemic glucocorticosteroids, and achievement of strong asthma control were determined.&#x0D; RESULTS: Of the 116 patients in the registry, 17.2% were stoppers and 12.1% were switchers. Stoppers suffered from chronic rhinosinusitis with nasal polyps less often and had an earlier asthma onset. Switchers had higher blood eosinophil levels. Therapy was canceled for personal reasons in 45% of the patients. The ineffectiveness of therapy in severe bronchial asthma and/or chronic rhinosinusitis with nasal polyps was the main reason for switching (92.8%) from omalizumab and benralizumab. The drug of choice for switching was dupilumab. Indicators improved, namely, ACT by 86.4%, AQLQ by 52.5%, SNOT-22 by 48%, and forced expiratory volume in the first second by 21.2%), and the need for systemic glucocorticosteroids decreased to 0 in 12 months after switching. Strong control was achieved in 62.5% of the patients when excluding the forced expiratory volume in the first second, and 50% of patients when including the forced expiratory volume in the first second.&#x0D; CONCLUSION: Careful selection of targeted therapy patients minimizes the failures of the starting drug to 12.1%. Switching the starting genetically engineered biological drug, aimed only at blocking eosinophils or only at blocking IgE, because of its inefficiency, to a drug with a dual mechanism of action leads to a significant improvement in ACT, AQLQ, SNOT-22, forced expiratory volume in the first second, and absence of systemic glucocorticosteroids.

Influence of Staphylococcal enterotoxin-specific IgE sensitization on therapeutic efficacy of omalizumab therapy in severe asthma.

Influence of Staphylococcal enterotoxin-specific IgE sensitization on therapeutic efficacy of omalizumab therapy in severe asthma.

Understanding Differential Response to Biologic Therapies in Severe Asthma: Retrospective study

Severe asthma, characterized by airway inflammation and debilitating symptoms, poses a significant challenge to millions of people worldwide. Traditional treatments for treating severe cases are limited, leading to the emergence of biologic therapies as promising alternatives. This retrospective cohort study from a tertiary hospital in Dubai aimed to explore the differential response to biologics in severe asthma patients and identify predictors of treatment outcomes. The baseline characteristics of 129 severe asthma patients receiving biologic therapy were analyzed, revealing a greater incidence of allergic diseases among responders. Multivariate Cox regression analysis revealed that early-onset asthma, urticaria, and rhinosinusitis (p =0.027, 0.037, and &lt;0.001, respectively) were predictors of a positive treatment response. Compared with non-responders, responders demonstrated improved asthma control, reduced exacerbations, and decreased oral corticosteroid usage. Despite the limitations inherent in retrospective studies, our findings underscore the significant clinical benefits of biologic therapy in severe asthma patients. Tailored treatment strategies based on patient characteristics and biologic class could optimize outcomes in this population, emphasizing the importance of personalized medicine in managing severe asthma. Further research into predictive biomarkers and larger cohort studies are warranted to validate these findings and enhance treatment efficacy in severe asthma management.

Articular manifestations related to anti-interleukin-5 therapies in severe asthma: a case series.

Articular manifestations should be screened before and during anti-IL-5/5R biologic treatment in severe asthma. Rigorous multidisciplinary team discussion should be carried out to assess the risk-benefit balance of withholding effective treatment. https://bit.ly/3vfPn4k.

Eosinophil to lymphocyte ratio may predict OCS reduction and change in quality of life (AQLQ) resulting from asthma biological treatment

Objectives Simple clinical parameters that could be helpful in choice of monoclonal antibodies and prediction of their effectiveness are being sought. The aim was to assess if neutrophil-to-lymphocyte, eosinophil-to-lymphocyte and platelet-to-lymphocyte ratios may predict outcomes of biologic therapy for severe asthma. Methods Retrospective, single-center study including severe asthma patients treated with three different biologics. The blood ratios were assessed at initiation of treatment (point 0) and after six months (point 1). The chi-square test was used to analyze differences in nominal variables. Quantitative variables were compared by Student’s t-test, Mann–Whitney U or Wilcoxon signed-rank tests. Results 53 patients with severe asthma were included, among them 21 patients (40%) treated with omalizumab and 32 patients (60%) with mepolizumab or benralizumab. Neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios did not change during six-month-course of biological treatment. Eosinophil-to-lymphocyte ratio was higher at the point 0 (p = 0.016) in the group treated with anti-eosinophils than in the omalizumab group and lower at the point 1 (p = 0.006). In the anti-eosinophil group this ratio decreased between points 0 and 1 (p < 0.001). In the omalizumab group there was an inverse correlation between the initial ratio and oral corticosteroid dose reduction (rs = −0,67). In the a/eos group there were significant correlations between initial ratio and age (rs = 0.36), and ACQ (rs = −0.4) and ACQ (rs = 0.41) measured at the point 1. Conclusions Pretreatment eosinophil-to-lymphocyte ratio may predict oral corticosteroid dose reduction resulting from omalizumab treatment and change in quality of life and asthma control resulting from anti-IL-5 and IL-5R treatment.

Should Airway Hyper-Responsiveness Be Included in the Definition of Clinical Remission With Biologic Therapy in Severe Asthma

Airway hyper-responsiveness (AHR) is a tenet of the persistent asthma phenotype along with reversible airway obstruction and type 2 (T2) inflammation. Indirect acting challenges such as mannitol are more closely related to the underlying T2 inflammatory process as compared with direct challenges. In this review article, we summarise the current literature and explore the future role of mannitol AHR in clinical remission with biologics.

The role of ACT score in mepolizumab discontinuation

Background Mepolizumab is a therapy for severe asthma. We have little knowledge of the characteristics of people in the US that discontinue mepolizumab in clinical care. Objective To investigate the real-world efficacy and time to clinical discontinuation of mepolizumab, we evaluated individuals with asthma started on mepolizumab at the Cleveland Clinic. We hypothesized that individuals that discontinue mepolizumab have more severe and uncontrolled asthma at baseline. Methods Between 2016 and 2022, patients who started on mepolizumab consented to be assessed over 18 months. At baseline, a questionnaire including demographic and medical history was collected. Laboratory findings such as ACT score, FENO (Fractional Excretion of Nitric Oxide), and spirometry were recorded. At the conclusion of the observation period, the participants were divided into two categories: Group A and Group B. Results Group B [N = 28] discontinued mepolizumab (p < 0.05) at an average of 5.8 months (SD 4.2 months). Group A [N = 129] stayed on the therapy for at least 1 year. A participant with an ACT score less than 13 has an odds ratio of 6.64 (95% CI, 2.1 − 26.0) of discontinuing mepolizumab therapy. For a male, the odds of discontinuing mepolizumab therapy is 3.39 (95% CI, 1.1–11.2). Conclusion In this real-world study, we find that high eosinophil count may not be adequate in screening which individuals will benefit from mepolizumab. Up to 17% of patients fail therapy within 6 months, with male sex and low ACT score increasing risk of mepolizumab discontinuation at Cleveland Clinic.