Biologics In Asthma Research Articles

Biological treatments in childhood asthma.

The aim is to update the information currently available for the use of biologics in severe asthma in children, in order to facilitate their prescription as far as possible. The appearance of biologics for the treatment of severe asthma has meant a revolutionary change in the therapeutic approach to this disease. Currently, five biologics have been approved for severe asthma in children and/or adolescents by the regulatory agencies: omalizumab, mepolizumab, benralizumab, dupilumab and tezepelumab. But despite their positive results in terms of efficacy, there are still relevant points of debate that should induce caution when selecting the most appropriate biologic in a child with severe asthma. Indeed, safety is essential and, for several of the existing treatments, the availability of medium-term to long-term data in this regard is scarce. The use of biologics can facilitate the therapeutic paradigm shift from pleiotropic treatments to personalized medicine. However, the choice of the most appropriate biologics remains a pending issue. On the other hand, to the extent that several of the biologics have been available for a relatively short time, the most robust evidence in terms of efficacy and safety in children is that of omalizumab.

Suboptimal Response to Biologics in Severe Asthma—A Marker of Humoral Immunodeficiencies

BackgroundAsthmatic patients with antibody deficiencies (AD) have more severe disease and higher risk of exacerbations. No data exists about the efficacy of biologics in severe asthma (SA) patients with AD.The objective of this study was to evaluate the efficacy of biologics in SA patients with and without AD. MethodsA case-control real-life study was conducted including 68 patients divided in two groups: group 1 with SA-AD and group 2 with SA. ResultsTreatment by biologics for 6 months was effective to decrease the number of exacerbations, hospitalizations, and emergency department (ED) visits, to improve the Asthma Control Questionnaire (ACQ) score and proved a systemic corticosteroid sparing effect. Despite benefits, the number of exacerbations, hospitalizations, and ED visits, the mean ACQ score, and the cumulative dose of systemic corticosteroids remain higher in group 1 vs 2, with lower lung function parameters. The rates of responses were inferior in group 1 vs 2 with a decrease by ≥50% of exacerbation rate in 76% vs 97% of patients (p=.006), no hospitalization in 44% vs 91% of patients (p<.001), no ED visit 56% vs 82% of patients (p=.018), significant improvement of ACQ score by ≥0.5 in 68% vs 100% of patients (p<.001), and increase of forced expiratory volume in the first second by >10% in 32% vs 65% of patients (p=.007). ConclusionDespite evident benefits, SA patients with AD have suboptimal responses to biologics compared to those immunocompetent. A multidisciplinary approach is necessary to optimize the management of these patients in practice.

Biologics for severe asthma.

Biologics for severe asthma.

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.

Comparative Impact of Asthma Biologics: A Nationwide US Claim-Based Analysis

BackgroundBiologic modifiers targeting type-2 (T2) airway inflammation are effective in reducing asthma exacerbation, however real-world and comparative effectiveness studies remain limited.Objective: to examine and compare the real-world impact of anti-T2 asthma biologics MethodsIn this retrospective new user cohort study, we used the MarketScan, a Commercial Claims and Encounters Database, to identify adult patients with asthma who were started on an anti-T2 biologic agent (anti-IL-5s, dupilumab or omalizumab). We examined the influence of the biologic class on asthma exacerbation by comparing the average number of asthma exacerbation 1-year pre- and post-biologic initiation. We conducted multivariable regression analyses to compare the effectiveness of these asthma biologics on reducing the incidence of asthma exacerbations within 18-month of initial administration of biologics while controlling for demographic variables, comorbidities, and asthma severity. ResultsWe identified 5,538 asthma patients who were initiated on an anti-T2 biologic [mean age (±SD); 45.6 (12.78) years; % females, 65.8%). Asthma biologics reduced asthma exacerbation by 11-47%, particularly among patients with 2+ asthma exacerbations in the year preceding biologic initiation (31-65% reduction). Biologics were especially effective in reducing asthma-related hospitalizations (44.6-60%). After adjusting for baseline demographics, asthma medication, and co-morbidities, dupilumab was associated with a lower estimated mean number of asthma exacerbation per year and lower adjusted OR for developing asthma exacerbation relative to other biologics (50-80% less likely). ConclusionAnti-T2 asthma biologics reduced asthma exacerbation in real-word settings. Evidence supports growing literature that dupilumab might have a more favorable impact on asthma exacerbation relative to other asthma biologics.

Precision care in the treatment of pediatric asthma.

Precision medicine in pediatric asthma involves identification of asthma phenotypes, genetic markers, biomarkers, and biologics that target specific pathways. This review includes a discussion of the efficacy of currently approved biologics for pediatric asthma and most recent advances in biomarker/phenotype identification and genetic associations that affect asthma care. Biologics targeting type-2 mediated pathways have shown success in the treatment of moderate to severe asthma in pediatric and adult patients. In comparative studies, dupilumab, an interleukin-4 (IL-4) alpha receptor inhibitor, and mepolizumab, an IL-5 inhibitor, have shown more improvement in asthma exacerbation rates and lung function compared to other biologics such as tezepelumab, omalizumab and benralizumab. Other methods used to categorize asthma treatment response have been investigated and include use of biomarkers such as fractional exhaled nitric oxide (FeNO). Genomic studies are also emerging in precision care for pediatric asthma. An understanding of underlying immunologic and genetic mechanisms affecting the development of asthma in pediatric patients has resulted in the production of numerous targeted therapies that have led to improvement in lung function and reduced exacerbation burden.

Impact of the ERS/ATS 2022 Guidelines for Interpretation of Lung Function Test Results When Assessing the Response to Biologics in Asthma.

Impact of the ERS/ATS 2022 Guidelines for Interpretation of Lung Function Test Results When Assessing the Response to Biologics in Asthma.

Clinical features in patients with COVID-19 treated with biologics for severe asthma

BackgroundFew studies have reported the clinical features of patients with coronavirus disease 2019 (COVID-19) who were treated with biologics for severe asthma (SA). ObjectiveTo elucidate the clinical features and mutual interaction between COVID-19 and SA in terms of disease severity during the Omicron epidemic. MethodsA retrospective study among patients with SA who received any biologic therapy from January 2022 to February 2023 at Jikei University Hospital (Tokyo, Japan) was performed. ResultsAmong 99 patients with SA, 22 women and 6 men suffered from COVID-19, and one woman was reinfected. The severity of COVID-19 was mild in 26 cases and moderate in 3. The number of vaccinations among patients with mild COVID-19 was significantly higher than that among patients with moderate COVID-19 (3.0 ± 1.4 vs. 1.0 ± 1.0, P = 0.03). Asthmatic exacerbations (AExs) were mild in 9 and moderate in 7 cases. The severity of AExs was significantly associated with the Asthma Control Test (ACT) score at baseline (no/mild/moderate exacerbation = 23.0 ± 2.3/18.1 ± 5.3/15.0 ± 4.3, respectively, P = 0.004, Kruskal‒Wallis test). By means of a multivariate logistic regression analysis, a lower number of vaccinations was a significant risk factor for COVID-19 progression [odds ratio 0.64 (0.46-0.91), P=0.006]. ConclusionDuring the Omicron epidemic, the onset and severity of COVID-19 were related to the number of vaccinations, and the severity of AExs caused by COVID-19 was associated with the ACT score at baseline and the number of vaccinations but not with the use of biologics.

Biologics for asthma and risk of pneumonia

Objective Modification of the immune system with biologics raises theoretical concerns about the risk of infections but it is still unclear whether currently routinely used biologics in severe asthma may facilitate the development of pneumonia. Therefore, we aimed to determine whether omalizumab, mepolizumab, benralizumab, and dupilumab are associated with pneumonia in a real-world setting. Methods A retrospective disproportionality analysis was performed using adverse event (AE) reports submitted to FAERS from January 2020 to September 30, 2023. MedDRA was used to identify infections and infestations and then pneumonia cases. ROR and PRR were used to measure disproportionality. Results The percentage of reported cases of pneumonia compared to infections and infestations was highest for mepolizumab (36.8%), followed by omalizumab (32.6%), benralizumab (19.2%) and dupilumab (5.7%). We found a moderate or strong signal for increased risk of pneumonia with mepolizumab (ROR = 3.74, 95%CI 3.50–4.00), omalizumab (ROR = 3.26, 95%CI 3.06–3.49) and benralizumab (ROR = 2.65, 95%CI 2.49–2.83). Conclusions Mepolizumab, omalizumab and benralizumab, but not dupilumab, were associated with high odds of reporting pneumonia. Our results represent only potential associations between these biologics and pneumonia but not causality. The nature of the FAERS database is such that the cause of the reported events is uncertain. Therefore, we can only roughly estimate the incidence of AEs by the signal strength (ROR value). Nevertheless, although causality could not be assessed, the signal from our study is interesting. We believe it deserves to be further substantiated by real-world studies with robust designs.

Anti-IL-5 and anti-IL-5R biologics for severe asthma. Are there any differences in their effects?

Objective The aim of this retrospective multicentre study is to describe the clinical characteristics of patients diagnosed with severe eosinophilic asthma receiving anti-IL-5/anti-IL-5Rα therapies and to compare their effectiveness. Methods We collected and analysed results separately for anti-IL-5 and anti-IL-5Rα therapies from January 2016 until December 2021 in multidisciplinary severe asthma units. We collected demographic and clinical data, treatment with previous anti-IgE and/or anti-IL-5 agents, and comorbidities. We compared the number of exacerbations and admissions to the hospital, daily oral corticosteroid intake, pulmonary function tests, and Asthma Control Test scores before and after 12 months of therapy. 261 patients were included: 176 patients in the anti-IL-5 group and 85 in the anti-IL-5Rα group. Results Both groups led to statistically significant reductions in asthma exacerbations, hospital admissions, and visits to the Emergency Room. Although both groups showed a significant reduction in blood eosinophiliccount, we found a difference, although not significant, in the magnitude of reduction as benralizumab was able to decrease eosinophil counts to zero. Patients in the anti-IL-5 group achieved higher ACT scores after treatment, although this improvement was seen in both treatment groups. Conclusion The anti-IL-5 and anti-IL-5Rα biologics have shown similar effectiveness despite having different mechanisms of action. The anti-IL-5 group appeared to be better than benralizumab at improving ACT scores and FEV1/FVC and at reducing the number of inhalers. Although these differences were not statistically significant, it is not clear whether they may have clinical relevance and they might highlight the need for further head-to-head studies comparing these treatments.

Tezepelumab in patients with allergic and eosinophilic asthma.

Asthma is a heterogeneous disease commonly driven by allergic and/or eosinophilic inflammation, both of which may be present in severe disease. Most approved biologics for severe asthma are indicated for specific phenotypes and target individual downstream type 2 components of the inflammatory cascade. Tezepelumab, a human monoclonal antibody (immunoglobulin G2λ), binds specifically to thymic stromal lymphopoietin (TSLP), an epithelial cytokine that initiates and sustains allergic and eosinophilic inflammation in asthma. By blocking TSLP, tezepelumab has demonstrated efficacy across known asthma phenotypes and acts upstream of all current clinically used biomarkers. In a pooled analysis of the phase 2b PATHWAY (NCT02054130) and phase 3 NAVIGATOR (NCT03347279) studies, compared with placebo, tezepelumab reduced the annualized asthma exacerbation rate over 52 weeks by 62% (95% confidence interval [CI]: 53, 70) in patients with perennial aeroallergen sensitization (allergic asthma); by 71% (95% CI: 62, 78) in patients with a baseline blood eosinophil count ≥300 cells/μL; and by 71% (95% CI: 59, 79) in patients with allergic asthma and a baseline blood eosinophil count ≥300 cells/μL. This review examines the efficacy and mode of action of tezepelumab in patients with allergic asthma, eosinophilic asthma and coexisting allergic and eosinophilic phenotypes.

A comparison of treatment response to biologics in asthma-COPD overlap and pure asthma: Findings from the PRISM study

BackgroundDespite the increasing use of biologics in severe asthma, there is limited research on their use in asthma-chronic obstructive pulmonary disease overlap (ACO). We compared real-world treatment responses to biologics in ACO and asthma. MethodsWe conducted a multicenter, retrospective, cohort study using data from the Precision Medicine Intervention in Severe Asthma (PRISM). ACO was defined as post-bronchodilator forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) <0.7 and a smoking history of >10 pack-years. Physicians selected biologics (omalizumab, mepolizumab, reslizumab, benralizumab, and dupilumab) based on each United States Food & Drug Administration (FDA) approval criteria. ResultsAfter six-month treatment with biologics, both patients with ACO (N = 13) and asthma (N = 81) showed positive responses in FEV1 (10.69 ± 17.17 vs. 11.25 ± 12.87 %, P = 0.652), Asthma Control Test score (3.33 ± 5.47 vs. 5.39 ± 5.42, P = 0.290), oral corticosteroid use (−117.50 ± 94.38 vs. −115.06 ± 456.85 mg, P = 0.688), fractional exhaled nitric oxide levels (−18.62 ± 24.68 vs. −14.66 ± 45.35 ppb, P = 0.415), sputum eosinophils (−3.40 ± 10.60 vs. −14.48 ± 24.01 %, P = 0.065), blood eosinophils (−36.47 ± 517.02 vs. −363.22 ± 1294.59, P = 0.013), and exacerbation frequency (−3.07 ± 4.42 vs. −3.19 ± 5.11, P = 0.943). The odds ratio for exacerbation and time-to-first exacerbation showed no significant difference after full adjustments, and subgroup analysis according to biologic type was also showed similar results. ConclusionsBiologics treatment response patterns in patients with ACO and asthma were comparable, suggesting that biologics should be actively considered for ACO patients as well.

Identification of biologic-responsive phenotypes in elderly people with eosinophilic asthma

Asthma in the elderly is not as well studied as in younger age groups. Age-related immunosenescence may result in diminished TH2 inflammation, which raises a question about whether asthma in elderly patients responds well to anti-TH2 asthma biologics. We sought to determine whether asthma in elderly people has different TH2 biomarkers and clinical features compared to nonelderly people, and if disease in the 2 age groups responds differently to anti-TH2 biologics. We also aimed to identify treatment-responsive phenotypes with clinical and biomarker features that could be used to predict best response to biologics. A retrospective chart review was conducted for 56 patients (30 elderly [age ≥62 years] and 26 nonelderly [ages 18-59 years] subjects) with severe asthma treated with dupilumab or benralizumab. Differences in baseline characteristics and response to treatment were analyzed. Ahierarchical cluster analysis was also performed to identify treatment-responsive phenotypes. Significance threshold was P= .05 for all analyses. Baseline characteristics and TH2 biomarkers (blood eosinophil level, total IgE, aeroallergen sensitivity) were similar between elderly and nonelderly subjects. The disease in both groups responded well to biologics (improvement in ACT scores, decreased exacerbations, decreased need for prednisone), but no significant response difference was found based on age groups. Cluster analysis identified 3 phenotypes, as follows: cluster 1, youngest age, moderate eosinophil levels, lowest total IgE, few environmental allergies, and least response to biologics; cluster 2, intermediate age, lowest eosinophil level, highest IgE level, many environmental allergies, and an intermediate response to biologics; and cluster 3, oldest ages, highest eosinophil levels, high total IgE, few environmental allergies, and best response to biologics. These results confirm trends seen in another study utilizing cluster analyses showing that subjects with highest levels of IgE and eosinophils responded better to biologic treatment for asthma. Elderly people with asthma should be considered for biologic therapy no differently than younger people. There may be subgroups of patients with different biologic responses based on age, allergenicity, IgE, and eosinophil levels that could be used to predict treatment response.

Managing Severe Adverse Reactions to Biologicals in Severe Asthma.

The use of biological agents in the treatment of various inflammatory and malignancy conditions has expanded rapidly. However, these agents can induce hypersensitivity reactions, posing significant clinical challenges. We conducted a retrospective study that included nine patients with severe asthma who experienced hypersensitivity reactions to biological agents (omalizumab, benralizumab and dupilumab). Hypersensitivity reactions to biologicals in severe asthma were observed in 9 of 68 patients treated. In five cases, treatment was stopped or changed to another available biological, and for four patients administered under close surveillance, titrated provocation or desensitization was applied. Successful desensitization was achieved in three of the patients, allowing them to continue therapy without adverse reactions. Improvements in asthma control were observed post-desensitization, leading to the reduced need for systemic steroid treatments and an increase in quality of life. This study highlights the importance of recognizing hypersensitivity reactions to biologicals to have an appropriate approach for patients with severe asthma. As an effective approach for patients experiencing hypersensitivity reactions to biological agents, desensitization allows treatment continuation.

Direct comparative study of the effectiveness of mepolizumab and dupilumab in patients with severe non-allergic eosinophilic asthma

Introduction. Biologics for severe asthma (SA) treatment are widely used in real clinical practice. But there are very few direct comparative studies at the moment.Aim. To compare mepolizumab and dupilumab effectiveness in patients with non-allergic eosinophilic SA in real clinical practice using regional register of Sverdlovsk region.Materials and methods. The data of patients with non-allergic eosinophilic SA treated with dupilumab (n = 23) and mepolizumab (n = 19) were analyzed. Therapy effectiveness was determined according to BARS and patients’ proportion who achieved asthma remission, dynamics of ACT, AQLQ, FEV1, blood eosinophils, frequency of short-acting bronchodilators use and systemic glucocorticosteroids (SGCS) demand, frequency of asthma exacerbations and hospitalizations.Results. Within 12 months of targeted therapy a good response to biologics according to BARS in 77.8% of patients on dupilumab and in 82.4% of patients on mepolizumab (p = 1.000) was revealed. Remission of SA (without FEV1) was achieved in 62.5% of patients in dupilumab group and in 68.8% of patients in mepolizumab group (p = 1.000). Remission of SA (with FEV1) was achieved in 43.8% of patients on dupilumab and in 56.2% of patients on mepolizumab (p = 0.724). There were statistically significant improvements for all separately analyzed indicators in each observation group. Statistically significant differences after a year of therapy between groups were recorded in terms of eosinophil levels (p &lt; 0.001) and nasal symptoms assessed using the SNOT-22 questionnaire (p = 0.048) in favour of mepolizumab.Conclusions. Patients with non-allergic eosinophilic SA have good response to both dupilumab and mepolizumab. The drugs equally improve disease control, life quality, reduce the need for relievers and SGCS, show a similar safety level.

Clinical remission in severe asthma with biologic therapy: an analysis from the UK Severe Asthma Registry.

Novel biologic therapies have revolutionised the management of severe asthma with more ambitious treatment aims. Here we analyse the definition of clinical remission as a suggested treatment goal and consider the characteristics associated with clinical remission in a large, real-world severe asthma cohort. This was a retrospective analysis of severe asthma patients registered in the UK Severe Asthma Registry (UKSAR) who met strict national access criteria for biologics. Patients had a pre-biologics baseline assessment and annual review. The primary definition of clinical remission applied included Asthma Control Questionnaire (ACQ)-5 <1.5 and no oral corticosteroids for disease control and forced expiratory volume in 1 s above lower limit of normal or no more than 100 mL less than baseline. 18.3% of patients achieved the primary definition of remission. The adjusted odds of remission on biologic therapy were 7.44 (95% CI 1.73-31.95)-fold higher in patients with type 2 (T2)-high biomarkers. The adjusted odds of remission were lower in patients who were female (OR 0.61, 95% CI 0.45-0.93), obese (OR 0.49, 95% CI 0.24-0.65) or had ACQ-5 ≥1.5 (OR 0.19, 95% CI 0.12-0.31) pre-biologic therapy. The likelihood of remission reduced by 14% (95% CI 0.76-0.97) for every 10-year increase in disease duration. 12-21% of the cohort attained clinical remission depending on the definition applied; most of those who did not achieve remission failed to meet multiple criteria. 18.3% of patients achieved the primary definition of clinical remission. Remission was more likely in T2-high biomarker patients with shorter duration of disease and less comorbidity. Further research on the optimum time to commence biologics in severe asthma is required.

A risk of serious anaphylatic reactions to asthma biologics: a pharmacovigilance study based on a global real-world database

Asthma is a chronic inflammatory condition that affects the lung airways. Chronic use of oral glucocorticoids in patients with severe asthma is associated with several adverse events (AEs). Biologics (omalizumab, benralizumab, mepolizumab, reslizumab, and dupilumab) have been developed as alternative therapies for the treatment of asthma. In this study, we aimed to evaluate the risk of anaphylactic reactions associated with these five biologics based on a large global database. We utilized individual case reports from the Uppsala Monitoring Center from January 1968 to December 29, 2019. A disproportionality analysis was performed over all drugs and monoclonal antibodies. Anaphylactic reactions were defined according to the "anaphylactic reaction” of the standardized MedDRA queries. Contrary to dupilumab, omalizumab, benralizumab, and mepolizumab demonstrated positive signals related to anaphylactic reactions over all drugs and monoclonal antibodies. Reslizumab, which represented only 315 cases of all AEs, requires more reports to determine its association with anaphylactic reactions. More anaphylactic reactions have been identified than are known, and most cases (96.2%) are reported to be serious. Our findings indicate that omalizumab, benralizumab, and mepolizumab for asthma treatment are associated with a high risk of anaphylactic reactions; thus, more careful monitoring in the post-administration period is recommended.

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.

Biologics in severe asthma: A pragmatic approach for choosing the right treatment for the right patient

The development of monoclonal antibody therapies targeting specific components of the pathways relevant to asthma pathophysiology has revolutionized treatment of severe asthma both in adults and children and helped to further unravel the heterogeneity of this disease. However, the availability of multiple agents, often with overlapping eligibility criteria, creates a need for pragmatic guidance for specialists undertaking care of patients with severe asthma. In this review, we provide an overview of the data supporting the clinical efficacy of biologics in distinct asthma phenotypes/endotypes. We also focus on the role of biomarkers and treatable traits, including comorbidities, in the choice of asthma biologics, highlight which treatments have been demonstrated to be steroid sparing in corticosteroid dependent asthma, and provide practical guidance that can drive shared decision making on treatment choice with patients. In addition, we summarize what is known to date regarding long-term safety of these drugs, and lastly, discuss future directions in biologics research.