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Presently, there are 6 biologic agents available for treatment of asthma. Each of these agents has undergone robust clinical trials in their approval programs. Such studies rely upon very rigid entry criteria that may not translate to real-world efficacy. Thus, exploring the efficacy of these agents in a larger, more heterogeneous, population brings a sense of comfort regarding their efficacy in the real-world. This review explores the available literature regarding the use of biologics in the real world, with a focus on markers of likely response to therapy., Competing Interests: Disclosures Dr M. Desai does not have any relevant disclosures. Dr J.J. Oppenheimer: DSMB, Adjudication: GSK, Sanofi/Regeneron, AZ, Amgen, Novartis, Consultant: GSK, Amgen, Bryn, ARS, UpToDate, Medscape, Annals of Allergy Asthma Immunology, ABAI., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: To evaluate the benefits of combining omalizumab with specific immunotherapy (SCIT) in the treatment of children with bronchial asthma., Methods: In this study, 83 children with asthma were treated at the Allergy Department of Qingdao University from January 2019 to February 2020. Participants were divided into three groups: SCIT, combination (omalizumab + SCIT), and control (standard asthma medications). We assessed Asthma Control Questionnaire (ACQ) scores, Visual Analogue Scale (VAS) scores, and lung function at baseline, 24 wk, and 48 wk. Additionally, asthma medication scores were compared at 24 and 48 wk. Adverse reactions were monitored in both the SCIT and combination groups., Results: The combination group demonstrated lower ACQ scores at both 24 and 48 wk, and improved VAS scores at 48 wk compared to the other groups. Additionally, lung function parameters (FEV1 and FEF50) showed significant improvement in the combination group. Reduced asthma medication scores were noted in the combination group at 24 and 48 wk. Local adverse reactions were fewer in the combination group, and no systemic adverse reactions were reported., Conclusion: Combining omalizumab with SCIT provides quicker asthma control, lowers medication requirements, and enhances lung function with fewer adverse effects, making it a safe and effective treatment for children with bronchial asthma.

Background: Clinical remission has recently been proposed as a possible treatment goal even in severe asthma. In this real-world study, we aimed to assess the achievement rate and predictive factors of clinical remission using omalizumab in patients with severe asthma., Methods: This retrospective observational study included patients with severe asthma initiated with omalizumab therapy and recruited from the asthma clinic of the Akdeniz University Hospital, Turkey. Clinical remission was defined as patients who received no oral corticosteroid (OCS) therapy; showed no exacerbations; showed an asthma control questionnaire score of ≤ 1, asthma control test (ACT) of ≥ 20, or both and, FEV 1 of ≥ 80% predicted., Results: A total of 58 patients were included in the study, with an average age of 56.4 ± 13.6 years. The mean duration of asthma was 23.5 ± 11.8 years and the mean duration of omalizumab treatment was 80.05 ± 35.04 months. Clinical remission rates were 25.9% in the first and second year, 34.0% in the third year, 34.1% in the fourth year and 47.4% in the fifth year. Pre-omalizumab ACT, FEV1 (%) and OCS use were significantly higher in patients with clinical remission at 1 year. Logistic regression analyses showed that none of the factors predicted clinical remission., Conclusion: Omalizumab has the potential to induce disease remission in a significant proportion of people with severe asthma, and this is maintained and improved over time.

Purpose: Research and regulatory approval for pediatric uses of prescription drugs often lag years after adult approvals, during which time substantial off-label use of medications in children can occur. We evaluated whether US Food and Drug Administration (FDA) regulatory actions affected the pediatric use of omalizumab, a biologic drug used to treat asthma., Methods: In this serial cross-sectional study, we identified quarterly cohorts of children (0-18 years) with moderate-to-severe asthma within two large national claims databases of those with commercial insurance and Medicaid from 2003 to 2019. Using an interrupted time-series analysis, we fit segmented linear regression models to identify changes in the incidence of omalizumab use in 6-11-year-old children compared with 12-18-year-olds after two time points: (1) 2009Q3 when an FDA advisory committee voted against use for 6-11-year-old children and (2) 2016Q2 when FDA expanded omalizumab's labeling to include 6-11-year-old children., Results: We identified 9298 new pediatric omalizumab users (84% Medicaid). Among 6-11-year-old children, the incidence of omalizumab use did not change following the FDA's initial review of evidence in 2009 and increased after 2016 Q2 FDA approval for this age group in both Medicaid (58 per 100 000 children with asthma, 95% confidence interval [CI] 27-89, p < 0.001) and commercial insurance (57 per 100 000, 95% CI 21-94, p = 0.003) compared with 12-18-year-old children., Conclusions: The use of omalizumab among asthmatic children aged 6-11 years remained steady after FDA advisory committee concerns in 2009 and increased after FDA expanded the indication to include this population in 2016. Additional market incentives may help to ensure the timely generation of evidence and regulatory approval of medications for children., (© 2024 John Wiley & Sons Ltd.)

Background: In recent years, there has been a growing interest in the utilization of biologic therapies for the management of asthma. Both TSLP and IgE are important immune molecules in the development of asthma, and they are involved in the occurrence and regulation of inflammatory response., Methods: A comprehensive search of PubMed and Web of Science was conducted to gather information on anti-TSLP antibody and anti-IgE antibody., Results: This investigation elucidates the distinct mechanistic roles of Thymic Stromal Lymphopoietin (TSLP) and Immunoglobulin E (IgE) in the pathogenesis of asthma, with a particular emphasis on delineating the therapeutic mechanisms and pharmacological properties of monoclonal antibodies targeting IgE and TSLP. Through a meticulous examination of clinical trials involving paradigmatic agents such as omalizumab and tezepelumab, we offer valuable insights into the potential treatment modalities for diseases with shared immunopathogenic pathways involving IgE and TSLP., Conclusion: The overarching objective of this comprehensive study is to delve into the latest advancements in asthma therapeutics and to provide guidance for future investigations in this domain., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

The success rate of omalizumab discontinuation is 50-75.5%. However, such data are scarce in Japan. We retrospectively investigated the clinical progression following the cessation of long-term omalizumab treatment (>5 years) in severe allergic asthma patients who have achieved super-responder status, defined as being off any oral maintenance corticosteroids without experiencing exacerbations requiring systemic corticosteroids for >1 year. Six (28.6%) among 21 patients recommenced after a median period of 5.5 (4.3-12.5) months later due to exacerbated asthma control, resulting in improved asthma management for all patients. The rates of patients who successfully remained off omalizumab treatment for 1 and 2 years were 72.4% and 65.8%, respectively. Specific IgE levels after discontinuing omalizumab treatment significantly decreased compared to those at initiating this treatment in 10 patients who successfully remained off this treatment. Therefore, discontinuing omalizumab treatment may be considered for patients continuing treatment beyond 5 years and achieving super-responder status., Competing Interests: Conflict of interest Satoshi Hamada reports a research grant from Teijin Pharma, outside the submitted work. Eriko Ogino and Hirotaka Yasuba have no conflict of interest., (Copyright © 2024 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)

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.

Summary: Background. Although biologic agents promise a short- to medium-term remission in asthma, it is unclear whether they can fundamentally alter disease course and achieve long-term remission. We aimed to investigate the clinical remission success of biologics in patients with severe asthma and the factors associated with remission. Methods. Adults followed-up due to severe asthma who were treated with mepolizumab or omalizumab were included in the study. Sociodemographic and clinical characteristics were reviewed. Subjects with and without clinical remission at 12 and 36 months were identified. Comparisons between the groups were made with univariate and multivariable analyses. Results. Seventy-four patients were included in the study. The mean age of subjects was 51.85 (standard deviation: 11.43) years, and 50 (67.57%) were females. The 12- and 36-month remission rates were 72.97% and 51.79%, respectively. Patients with and without remission were similar in terms of age and gender distribution. FEV1% predicted (p = 0.009) and FEV1/FVC ratio (p = 0.039) were significantly higher in those with remission at 12 months compared to those without. FEV1 (p less than 0.001), FEV1% predicted (p less than 0.001) and FEV1/FVC ratio (p = 0.004) were significantly higher in those with remission at 36 months compared to those without. Multivariable logistic regression revealed that higher FEV1% predicted was the only factor independently associated with remission for both time points. Conclusions. Omalizumab and mepolizumab provide significant clinical remission rates in severe asthma. FEV1% predicted is a variable that can independently predict clinical remission among severe asthmatics receiving biologic agents.

Background: Some patients with severe asthma may benefit from treatment with biologics, but evidence has been mostly collected from randomized controlled trials (RCTs), in which patients' characteristics are different from those encountered in asthma patients in the real-world setting. The aim of this study was to describe the clinical features of complete responders versus non-complete responders to long-term treatment with biologics in patients with severe asthma attended in routine daily practice., Methods: Data of a cohort of 90 patients with severe asthma who were treated with biologics (omalizumab, benralizumab, and mepolizumab) for at least 12 months and were followed up to March 2022. Data recorded included clinical characteristics and effectiveness of treatment (exacerbation, Asthma Control Test [ACT] score, lung function, use of maintenance oral corticosteroids [mOCS]), FeNO, and blood eosinophils at baseline, at 12 months, and at the end of follow-up. Complete response is considered if, in addition to not presenting exacerbations or the use of mOCS, the ACT score was >20 and, the FEV 1 >80% predicted., Results: An improvement in all asthma control parameters was observed after 12 months of treatment and a mean follow-up of 55 months. After 12 months of treatment 27.2% of patients met the criteria of complete response and this percentage even increased to 35.3% at the end of follow-up. Long-term complete response was associated to better lung function with mepolizumab and omalizumab treatment and to less previous exacerbations in the benralizumab group. The main cause of not achieving a complete response was the persistence of an airflow obstructive pattern., Conclusions: This study shows that omalizumab, benralizumab, and mepolizumab improved the clinical outcomes of patients with severe asthma in a clinic environment with similar effect sizes to RCTs in the long term follow-up. Airflow obstruction, however, was a predictor of a non-complete response to biologics.

Introduction: A minority of school-aged children with asthma have persistent poor control and experience frequent asthma attacks despite maximal prescribed maintenance therapy. These children have higher morbidity and risk of death. The first add-on biologic therapy, omalizumab, a monoclonal antibody that blocks immunoglobulin (Ig)E, was licensed for children with severe asthma in 2005. While omalizumab is an effective treatment, non-response is common. A second biologic, mepolizumab which blocks interleukin 5 and targets eosinophilic inflammation, was licensed in 2018, but the licence was granted by extrapolation of adult clinical trial data to children. This non-inferiority (NI) trial will determine whether mepolizumab is as efficacious as omalizumab in reducing asthma attacks in children with severe therapy resistant asthma (STRA) and refractory difficult asthma (DA)., Methods and Analysis: This is an ongoing multicentre 1:1 randomised NI open-label trial of mepolizumab and omalizumab. Up to 150 children and young people (CYP) aged 6-17 years with severe asthma will be recruited from specialist paediatric severe asthma centres in the UK. Prior to randomisation, children will be monitored for medication adherence for up to 16 weeks to determine STRA and refractory DA diagnoses. Current prescribing recommendations of serum IgE and blood eosinophils will not influence eligibility or enrolment. The primary outcome is the 52-week asthma attack rate. Bayesian analysis using clinician-elicited prior distributions will be used to calculate the posterior probability that mepolizumab is not inferior to omalizumab. Secondary outcomes include Composite Asthma Severity Index, Paediatric Asthma Quality of Life Questionnaire, lung function measures (forced expiratory volume in one second (FEV1), bronchodilator reversibility), fractional exhaled nitric oxide, Asthma Control Test (ACT), health outcomes EuroQol 5 Dimension (EQ-5D) and optimal serum IgE and blood eosinophil levels that may predict a response to therapy. These outcomes will be analysed in a frequentist framework using longitudinal models., Ethics and Dissemination: The study has been approved by the South Central-Berkshire Research Ethics Committee REC Number 19/SC/0634 and had Clinical Trials Authorisation from the Medicines and Healthcare Products Regulatory Agency (MHRA) (EudraCT 2019-004085-17). All parents/legal guardians will give informed consent for their child to participate in the trial, and CYP will give assent to participate. The results will be published in peer-reviewed journals, presented at international conferences and disseminated via our patient and public involvement partners., Trial Registration Number: ISRCTN12109108; EudraCT Number: 2019-004085-17., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

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

Background: Mepolizumab is an anti-interleukin-5 monoclonal antibody shown to reduce asthma exacerbations in adults and adolescents with severe eosinophilic asthma., Aim: To assess the impact of mepolizumab on children and adolescents over 12 months by examining steroid usage, asthma-related hospitalizations, Asthma Control Test (ACT) scores, fractional exhaled nitric oxide concentration (FeNO), forced expiratory volume in 1 s (FEV 1 ), mid expiratory flow (FEF 25-75% ), and blood eosinophil count., Methods: Retrospective analysis performed between October 2015 and December 2022. Data was reviewed 12 months before and after commencing mepolizumab. Mepolizumab was offered if the patient had severe eosinophilic asthma and were unresponsive to or ineligible for omalizumab., Results: Sixteen participants (age 7-17, 8 males, 8 females) received subcutaneous mepolizumab monthly with no serious adverse reactions. Incidence of hospital admissions fell significantly (IRR 0.33, p  = 0.007). Among the 11 patients receiving daily oral corticosteroids, 3 were weaned off daily oral steroids and 3 patients' daily dose was significantly reduced (mean Δ-0.095 ± 0.071 mg/kg, p  = 0.0012). Eosinophil count was decreased (mean Δ-0.85 x 10 9 /L, p  < 0.001). There was no significant change in mean overall steroid burden per patient (mean Δ-1445.63 ± 1603.18 mg, p  = 0.10), ACT scores (mean Δ2.88 ± 6.71, p  = 0.17), FEV 1 z-scores (mean Δ-0.99 ± 1.88, p  = 0.053), FEF 25-75% z-scores (mean Δ-0.65 ± 1.61, p  = 0.13), FeNO (mean Δ-20.09 ± 80.86, p  = 0.34), or number of courses of oral steroids given for asthma attacks (IRR 0.71, p  = 0.09)., Conclusion: Among children and adolescents with severe eosinophilic asthma ineligible for or not responsive to omalizumab, mepolizumab therapy exhibited significant reduction in rate of asthma-related hospitalizations and significant decrease in daily steroid dosage.

Background and Aims: Allergic asthma has a considerable burden on the quality of life. A significant portion of moderate-to-severe allergic asthma patients need omalizumab, an anti-immunoglobulin-E monoclonal antibody, as an add-on therapy. In this phase III clinical trial P043 (Zerafil ® , CinnaGen, Iran) efficacy, safety, and immunogenicity were compared with Xolair ® (the originator omalizumab). The primary outcome was the rate of protocol-defined asthma exacerbations., Methods: Exacerbation rates, Asthma Control Test (ACT) results, spirometry measurements, immunogenicity, and safety were evaluated. Each subject received either medication with a dose ranging from 150 to 375 mg based on pre-treatment serum total IgE level (IU/mL) and body weight (kg) every two or four weeks for a duration of 28 weeks., Results: Exacerbation rates were 0.150 (CI: 0.079-0.220) in the P043 group, and 0.190 (CI: 0.110-0.270) in the omalizumab group (per-protocol). The least squares mean differences of predicted Forced Expiratory Volume in the First second (FEV 1 ) were -2.51% (CI: -7.17-2.15, P=0.29) and -3.87% (CI: -8.79-1.04, P=0.12), pre- and post-bronchodilator use. The mean ± SD of ACT scores at the screening and the last visit were 10.62 ± 2.93 and 20.93 ± 4.26 in P043 and 11.09 ± 2.75 and 20.46 ± 5.11 in the omalizumab group. A total of 288 adverse events were reported for the 256 enrolled participants. Among all, "dyspnea" and "headache" were the most reported ones. The overall incidence of adverse events (P=0.62) and serious adverse events (P=0.07) had no significant differences between the two groups. None of the samples were positive for anti-drug antibodies., Conclusion: P043 was equivalent to omalizumab in the management of asthma in reduction of exacerbations. There was no significant difference in other efficacy and safety parameters., Clinical Trial Registration: www.clinicaltrials.gov (NCT05813470) and www.IRCT.ir (IRCT20150303021315N20)., Competing Interests: Author BG has received educational grants from AstraZeneca, Abidi, and Sanofi. Author MM has received research grants from Koushan Pharmed. Authors HR and DA have received research grants from AstraZeneca. Author MF has received research grants from Abidi. Author AK has received lecture honorarium from AstraZeneca. Author FJ has received research grants from Zist Takhmir and Vitabiotics. Author ST has received travel supports to attend scientific meetings from Novartis, GSK, and AstraZeneca. Author MH has collaborated with Jaber-ebne-hayyan. Author MRF has collaborated with Pooyesh darou. Author HK is the head of the medical department of Orchid Pharmed Company; which is in collaboration with CinnaGen company with respect to conducting clinical trials. Author AS is a member of CinnaGen medical biotechnology research center, which collaborates with universities and researchers all over the world with regards to research and development of medications and health issues. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. This study was supported by CinnaGen Company by grant number of 701/373. The sponsor also had participated in the conduction of the study., (Copyright © 2024 Ghanei, Ghalebaghi, Sami, Torabizadeh, Mirsadraee, Amra, Tavakol, Raji, Fallahpour, Kiani, Abedini, Jabbari Azad, Mahdaviani, Attaran, Samet, Tavana, Haddadzadeh shoushtari, Nazari, AghaeiMeybodi, Fazlollahi, Ghasemi, Sabzvari, Kafi and Idani.)

Background: Biologic 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., Methods: In this retrospective, new user cohort study, we used the MarketScan, a Commercial Claims and Encounters Database, to identify adult patients with asthma who began to receive 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 before and after biologic initiation. We conducted multivariable regression analyses to compare the effectiveness of these asthma biologics on reducing the incidence of asthma exacerbations within 18 months of the initial administration of biologics while controlling for demographic variables, comorbidities, and asthma severity., Results: We identified 5,538 asthma patients who were new to taking an anti-T2 biologic [mean age [±SD], 45.6 (12.78) years; 65.8% female). Asthma biologics reduced asthma exacerbation by 11% to 47%, particularly among patients with two or more asthma exacerbations in the year preceding biologic initiation (31% to 65% reduction). Biologics were especially effective in reducing asthma-related hospitalizations (44.6% to 60%). After adjusting for baseline demographics, asthma medication, and comorbidities, dupilumab was associated with a lower estimated mean number of asthma exacerbation per year and lower adjusted odds ratio for developing an asthma exacerbation relative to other biologics (50% to 80% less likely)., Conclusions: Anti-T2 asthma biologics reduced asthma exacerbation in real-word settings. Evidence supports growing literature reporting that dupilumab might have a more favorable impact on asthma exacerbation relative to other asthma biologics., (Copyright © 2024 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Objective: The combination of allergen immunotherapy (AIT) and omalizumab is used to treat patients at risk of anaphylaxis. There is currently a very little evidence that this combination increases the effectiveness of AIT in patients with inhalant allergies. The study aimed to evaluate the effectiveness of HDM-SCIT therapy (injection immunotherapy for house dust mites) in combination with omalizumab in treating HDM-induced asthma., Methods: This study was a placebo-controlled, randomized, multicenter trial including 82 patients with HDM-driven mild to moderate asthma. Omalizumab alone (A), HDM SCIT + omalizumab (B), SCIT alone (C), or placebo (D) for 24 months were applied. All patients received asthma treatment in accordance with GINA recommendations. The treatment efficacy was defined by a reduction in the daily dose of inhaled steroids (ICS) and a reduction in the number of asthma exacerbations (AX)., Results: After 24 months of therapy, a statistically significant reduction in the daily doses of ICS in groups A and B was observed ( p  = 0.021 and p  = 0.008). Daily ICS reduction was considerably more significant in group B ( p  = 0.01). During 24 months of observation, the AX was significantly reduced in all study groups, with the greatest significant difference observed between groups A and B and groups C and D (placebo) as follows: 0.42 patient/per year vs. 0.39 vs. 0.84 vs. 0.91 ( p  = 0.023)., Conclusion: The combination of HDM SCIT and omalizumab is significantly and progressively reducing ICS use and AX in a 24-month study. The combination is significantly more effective than the single treatments or placebo.

Purpose of Review: 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., Recent Findings: 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., Summary: 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., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

The prevalence of asthma among the elderly population has witnessed a notable rise, presenting unique challenges in diagnosis and management. Biologic therapies, such as omalizumab, mepolizumab, reslizumab, benralizumab, dupilumab, and tezepelumab, have demonstrated efficacy in targeting specific pathways associated with severe asthma in elderly individuals. However, a significant research gap exists in the application of these therapies in elderly asthma patients. Despite the considerable size of the elderly asthma population and the social and economic burden that this specific demographic imposes on society, the available body of research catering to this group is limited. Notably, no RCTs have been expressly designed for the elderly across all asthma biologic therapies. Moreover, most RCTs have set upper age cutoffs, commonly 75 years old, and exclusion criteria for common comorbidities in the elderly, thus marginalizing this group from pivotal research. This underscores the crucial need for intentional inclusion of elderly participants in separately designed clinical trials and more researches, aiming to augment the generalizability of findings and enhance therapeutic outcomes. Given the distinct physiological changes associated with aging, there may be a concern regarding the efficacy and safety of biologic therapies in the elderly compared to non-elderly adults, posing a barrier to their use in this population. However, observational studies have shown similar benefits of these therapies in elderly individuals as seen in non-elderly adults. Other anticipated challenges related to initiating biologic therapy in elderly people with asthma including dosing consideration and monitoring strategies, which are important areas of investigation for optimizing asthma management will be discussed in this review. In summary, this review navigates the current landscape of biologic therapies for elderly asthma, offering valuable insights for various stakeholders, including researchers, healthcare providers, and policymakers, to advance asthma care in this vulnerable population. We propose that future research should concentrate on tailored, evidence-based approaches to address the undertreatment of elderly asthma patients., Competing Interests: Declaration of competing interest All authors have no conflict of interest to report., (Copyright © 2024. Published by Elsevier Ltd.)

Background: 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., Objective: 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., Methods: 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)., Results: 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., Conclusions: 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., (© 2024. The Author(s).)

Introduction: Asthma is a pathology that remains severe and is inadequately controlled in 4% of patients. Identification of multiple pathophysiological mechanisms has led to the development of biomedicines, of which there are currently five available in France, with a safety profile that appears favorable but remains uncertain due to a lack of real-life experience with these new molecules., State of Knowledge: Although relatively benign, the adverse effects of biologics are diverse. Headache, joint pain, skin reactions at the injection site, fever and asthenia are commonly observed during the different treatments. Ophthalmological complications seem restricted to dupilumab, with numerous cases of keratitis and conjunctivitis in patients with atopic dermatitis. Several respiratory complications have also been observed, essentially consisting in pharyngitis and other upper respiratory infections. Hypereosinophilia may occur, mainly with dupilumab, requiring investigation of systemic repercussions or vasculitis. Allergic reactions are uncommon but require careful monitoring during initial injections., Conclusion: Biologics for severe asthma are recent drugs with a favorable safety profile, but with little real-life experience, justifying increased vigilance by prescribing physicians., (Copyright © 2024 SPLF. Published by Elsevier Masson SAS. All rights reserved.)

Background: Lung function is an independent predictor of mortality. We evaluated the lung function trajectories of a cohort of patients with asthma receiving biologic therapy., Methods: We identified 229 monoclonal antibody-naïve adult patients with moderate-to-severe asthma who initiated omalizumab, mepolizumab, or dupilumab between 2010 and 2022 in a large healthcare system in Boston, MA. Generalized additive mixed models were used to estimate the lung function trajectories during the 156 weeks following biologic initiation. Response was defined as an improvement in FEV 1 or a decrease of ≤0.5% per year. The Kaplan-Meier estimator was used to assess time to no additional improvement in FEV 1 in responders. All models were adjusted for age, sex, body mass index, smoking status, baseline exacerbation rate, and baseline blood eosinophil count., Results: Eighty-eight patients initiated mepolizumab, 76 omalizumab, and 65 dupilumab. Baseline eosinophil count was highest in the mepolizumab group (405 cells/mcL) and lowest for omalizumab (250 cells/mcL). Both FEV 1 and FVC improved in the mepolizumab group (FEV 1  + 20 mL/year; FVC +43 mL/year). For omalizumab, there was an initial improvement in the first year followed by decline with an overall FEV 1 loss of -44 mL/year and FVC -32 mL/year. For dupilumab, both FEV 1 (+61 mL/year) and FVC (+74 mL/year) improved over time. Fifty percent of the mepolizumab group, 58% omalizumab, and 72% of dupilumab were responders. The median time to no additional FEV 1 improvement in responders was 24 weeks for omalizumab, 48 weeks for mepolizumab, and 57 weeks for dupilumab., Conclusion: In this clinical cohort, mepolizumab, omalizumab, and dupilumab had beneficial effects on FEV 1 and FVC with distinct post-initiation trajectories., (© 2024 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Background: Omalizumab is a humanized monoclonal antibody that specifically binds to free human immunoglobulin E. The introduction of this drug raises concerns about economic impact in scenarios with constrained. This study aimed to estimate the cost utility of omalizumab in adults with severe asthma uncontrolled in Colombia., Methods: We used a Markov state-transition model to estimate the cost and QALYs associated with omalizumab compared to standard of care; from a third payer perspective over a lifetime horizon. This model used local costs while utilities were derived from international literature. Cost and transition probabilities were obtained from a mixture of Colombian-specific and internationally published data., Results: The mean incremental cost of omalizumab versus standard of care is US$3 481. The mean incremental benefit of omalizumab versus standard of care 0.094 QALY. The incremental expected cost per unit of benefit is estimated at US$36846 per QALY. There is only a probability of 0.032 that Omalizumab is more cost-effective than standard of care at a threshold of US$5180 per QALY., Conclusion: Omalizumab is not cost-effective in adults with severe asthma uncontrolled in Colombia. If the cost of Omalizumab is reduced by 83%, this treatment would be cost-effective in our country. Our study provides evidence that should be used by decision-makers to improve clinical practice guidelines and should be replicated to validate their results in other middle-income countries.

Background: Cost-effectiveness studies evaluate health technologies and help choose treatments. The current study compared dupilumab to omalizumab, mepolizumab, and benralizumab in Colombian adults with severe uncontrolled type 2 asthma., Methods: Over a 5-year period, a Markov model was utilized to assess the costs of biological treatments and management of exacerbations, comparing various doses of exacerbations, comparing various doses of dupilumab, omalizumab, mepolizumab, and benralizumab as add-on treatments. It included a 5% annual discount rate per local HTA, and set willingness-to-pay at three times GDP per capita per quality-adjusted life year (QALY) in Colombia., Results: Dupilumab (200 mg) exhibited greater QALYs and reduced overall costs compared to mepolizumab (100 mg), benralizumab (30 mg), and omalizumab (450 mg and 600 mg), with the incremental cost-effectiveness ratio (ICER) per QALYgained being -$5.429, -$6.269, -$196.567 and -$991.007, respectively. Dupilumab had greater QALYs and costs versus omalizumab 300 mg (ICERof $200.653 per QALY, above the willingness-to-pay threshold of 3 × GDP per capita). Sensitivity analyses were consistent with base case results., Conclusions: Dupilumab 200 mg was strongly dominant versus omalizumab 450 mg and 600 mg, mepolizumab 100 mg, and benralizumab 30 mg; however, cost-effectiveness was not demonstrated versus omalizumab 300 mg. These results could assist healthcare professionals in choosing an appropriate biologic for treating severe type 2 asthma.

For patients with moderate-to-severe persistent allergic asthma, omalizumab is approved for subcutaneous administration according to a recommended dosing table based on weight and total immunoglobulin E (IgE) level. The aim of this analysis was to assess asthma outcomes including quality of life in patients with allergic asthma initiated on omalizumab in the PROSPERO trial; patients were stratified by where their IgE and body weight fell on the approved dosing table. Patient groups were defined as Inside Dosing Table: patients whose IgE and weight fell within the approved dosing table (n = 506); Insufficient Data to Recommend a Dose: patients who fell into the section of the approved dosing table where not enough clinical data were available to make dosing recommendations (n = 72); and Outside Dosing Table: patients who fell outside the approved dosing table due to baseline IgE and/or weight (n = 209). Overall, asthma and quality of life outcomes were improved after omalizumab initiation for both patients who fall within the recommended dosing table or those who fall outside the recommended dosing table. Our results suggest that omalizumab treatment may be effective in a wide range of patients with moderate-to-severe allergic asthma. ClinicalTrials.gov identifier NCT01922037., Competing Interests: Declaration of competing interest NMC: consultant and/or speaker bureau member for Amgen, ARS Pharmaceuticals Inc., AstraZeneca, Blueprint Medicines, Bryn Pharma, Genentech Inc., GlaxoSmithKline, Hikma Pharmaceuticals, Incyte, Novartis, Regeneron, and Sanofi; speaker bureau member for Incyte; consultant for ARS Pharmaceuticals Inc., Bryn Pharma, Genentech, Inc., Hikma Pharmaceuticals, and Novartis Pharmaceuticals Corporation. ML: institution received research grant support on her behalf from Sanofi; received honoraria for serving as a consultant for AstraZeneca. CTJH: former employee of Genentech, Inc. LAM, AS, JWS, BLT: employees of Genentech, Inc.; stockholders of Roche. NAH: received honoraria for serving as advisor or consultant for Amgen, AstraZeneca, Genentech, Inc., GlaxoSmithKline, Novartis Pharmaceuticals Corporation, Regeneron, Sanofi, and Teva. Institution received research grant support on his behalf from AstraZeneca, Genentech, Inc., GlaxoSmithKline, Novartis, Sanofi, and Teva. TBC: consultant and speaker bureau member for Genentech, Inc.; consultant for Novartis Pharmaceuticals Corporation; chief medical advisor for Food Allergy Research & Education., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Asthma is one of the most common diseases in children, with a variable range of severity. In recent years, treatment for severe asthma has been largely improved by the availability of targeted biologic therapies. Nevertheless, studies reporting real-world data and cost-effectiveness analyses are lacking. The aim of this study was to evaluate, on a population-based cohort of children with asthma, the impact of the treatment with biologics on healthcare service utilization and associated costs., Methods: Data were retrieved from Healthcare Utilization database of Lombardy region (Italy). A cohort of 46 asthmatic children aged 6-11 in treatment with dupilumab, mepolizumab or omalizumab was identified during 2017-2021. We compared healthcare resources use between the year before ("baseline period") and the year after the treatment initiation ("follow-up period"). Average 1-year healthcare costs were also calculated., Results: Comparing the baseline with the follow-up period, the number of patients with at least one exacerbation-related hospitalization and ER access decreased by 75.0% and 85.7%, respectively. The use of biologic agents, namely omalizumab, mepolizumab and dupilumab, significantly reduced oral corticosteroids (OCS), short-acting β2-agonists and the association inhaled corticosteroids/long-acting β2-agonists use. ER admissions for non-respiratory causes were also significantly reduced, while discontinuation rate was low (6.5%). The overall costs increased, due to the costs of the biologic agents, but the hospital admission-related costs due to respiratory causes reduced significantly., Conclusions: Our real-world investigation suggests that biologic agents reduced hospital admissions for respiratory causes and use of anti-asthmatic drugs, including OCS. However, long-term healthcare sustainability still needs more in-depth assessments., (© 2023 The Authors. Pediatric Pulmonology published by Wiley Periodicals LLC.)

Background: The concept of remission on biological treatment has been suggested as a therapeutic target for patients with severe asthma, composed of 1. no chronic use of systemic steroids, 2. no exacerbations, 3. minimal symptoms, and 4. optimized lung function, for a significant time. However, the criteria for remission are not clearly defined., Objective: Our objective was to compare different criteria for remission in subjects receiving biologicals for severe asthma., Methods: A cross-sectional study of adult subjects who receive a stable regimen of a biological for severe asthma for at least 6-months. We compared the proportion of subjects who fulfilled different specific criteria in the four domains, as well as those who achieved different composite outcome measures of clinical remission., Results: Of 39 subjects, 28 were females (71.8%), mean age 60.4. Twelve were current or past smokers (30.8%). Twelve had prior different biological treatment (30.8%), and 3/39 had more than one previous treatment (7.7%). Current biological included mepolizumab 12/39 (30.8%), dupilumab 11/39 (28.2%), benralizumab 10/39 (25.6%), omalizumab 5/39 (12.8%), reslizumab 1/39 (2.6%). Different specific criteria were achieved in 39-80% of subjects, being highest for no chronic steroid use and lowest for symptoms control and lung function. Overall remission was obtained by 20-41%, depending on definition, with significant variability in agreement between different sets of remission criteria (Cohen's kappa 0.33-0.89)., Conclusion: Clinical remission is achievable in real-world severe asthmatics on biological therapies. The core criteria for remission should be better defined., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Ori Wand reports a relationship with GlaxoSmithKline that includes: consulting or advisory and speaking and lecture fees. Ori Wand reports a relationship with AstraZeneca that includes: consulting or advisory and speaking and lecture fees. Ori Wand reports a relationship with Boehringer Ingelheim Ltd that includes: speaking and lecture fees. Ori Wand reports a relationship with Sanofi that includes: speaking and lecture fees. Ori Wand reports a relationship with Kamada Ltd that includes: speaking and lecture fees. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Asthma remission has emerged as a potential treatment goal. This study evaluated the effectiveness of two biologics (mepolizumab/omalizumab) in achieving asthma remission., Methods: This observational study included 453 severe asthma patients (41% male; mean age ± SD 55.7 ± 14.7 years) from two real-world drug registries: the Australian Mepolizumab Registry and the Australian Xolair Registry. The composite outcome clinical remission was defined as zero exacerbations and zero oral corticosteroids during the previous 6 months assessed at 12 months and 5-item Asthma Control Questionnaire (ACQ-5) ≤1 at 12 months. We also assessed clinical remission plus optimization (post-bronchodilator FEV1 ≥80%) or stabilization (post-bronchodilator FEV1 not greater than 5% decline from baseline) of lung function at 12 months. Sensitivity analyses explored various cut-offs of ACQ-5/FEV1 scores. The predictors of clinical remission were identified., Results: 29.3% (73/249) of AMR and 22.8% (37/162) of AXR cohort met the criteria for clinical remission. When lung function criteria were added, the remission rates were reduced to 25.2% and 19.1%, respectively. Sensitivity analyses identified that the remission rate ranged between 18.1% and 34.9% in the AMR cohort and 10.6% and 27.2% in the AXR cohort. Better lung function, lower body mass index, mild disease and absence of comorbidities such as obesity, depression and osteoporosis predicted the odds of achieving clinical remission., Conclusion: Biologic treatment with mepolizumab or omalizumab for severe asthma-induced asthma remission in a subgroup of patients. Remission on treatment may be an achievable treatment target and future studies should consider remission as an outcome measure., (© 2023 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

This article presents the experience of successfully switching therapy from omalizumab 150 mg to benralizumab 30 mg/1 ml in a patient with a combined allergic and eosinophilic phenotype in the presence of hypersensitivity to nonsteroidal anti-inflammatory drugs. The effectiveness of biological therapy was evaluated when switching from omalizumab 150 mg subcutaneously at a dose of 600 mg for 36 weeks. Therapy for the drug benralizumab 30 mg/1 ml subcutaneously the first three injections monthly, the rest a month later for 52 weeks with bronchial asthma (BA), a severe uncontrolled course with a combined allergic and eosinophilic phenotype in the presence of hypersensitivity to nonsteroidal anti-inflammatory drugs in a patient Ch., born in 2004. Switching therapy from omalizumab 150 mg to benralizumab 30 mg/1 ml allowed to achieve complete control of asthma symptoms (AST = 23 points), to achieve the absence of asthma exacerbations during 52 weeks, restore respiratory function to normal values, as well as improve the quality of life. The study reflects the good tolerability, high efficacy and safety of biological therapy when switching from one genetically engineered biological drug (GIBP) omalizumab 150 mg to another GIBP benralizumab 30 mg/1 ml in severe uncontrolled asthma with a combined allergic and eosinophilic phenotype in the presence of hypersensitivity to nonsteroidal anti-inflammatory drugs. Therapy with benralizumab 30 mg/1 ml in severe BA has demonstrated a more effective clinically significant improvement in the course of the disease, control of symptoms of the disease. Reduction of exacerbations, normalization of respiratory function indicators, complete control of the disease has been achieved. Consequently, the use of different biological molecules for the therapy of BA with a combined allergic and eosinophilic phenotype contributes to achieving disease control, improving the patient's quality of life and reducing the dose of oral glucocorticosteroids. The targeted biological drug benralizumab 30 mg/1 ml has a targeted effect on the key links in the pathogenesis of severe uncontrolled asthma with a combined allergic and eosinophilic phenotype in the presence of hypersensitivity to nonsteroidal anti-inflammatory drugs and reduces the burden of severe disease.

Objective: Asthma is a major global disease affecting adults and children, which can lead to hospitalization and death due to breathing difficulties. Although targeted monoclonal antibody therapies have revolutionized treatment of severe asthma, some patients still fail to respond. Here we critically evaluate the literature on biologic therapy failure in asthma patients with particular reference to anti-drug antibody production, and subsequent loss of response, as the potential primary cause of drug failure in asthma patients., Recent Findings: Encouragingly, asthma in most cases responds to treatment, including the use of an increasing number of biologic drugs in moderate to severe disease. This includes monoclonal antibody inhibitors of immunoglobulin E and cytokines, including interleukin 4, 5, or 13 and thymic stromal lymphopoietin. These limit mast cell and eosinophil activity that cause the symptomatic small airways obstruction and exacerbations., Summary: Despite humanization of the antibodies, it is evident that benralizumab; dupilumab; mepolizumab; omalizumab; reslizumab and tezepelumab all induce anti-drug antibodies to some extent. These can contribute to adverse events including infusion reactions, serum sickness, anaphylaxis and potentially disease activity due to loss of therapeutic function. Monitoring anti-drug antibodies (ADA) may allow prediction of future treatment-failure in some individuals allowing treatment cessation and switching therefore potentially limiting disease breakthrough.

Introduction: Non-steroidal anti-inflammatory drug-exacerbated respiratory disease (N-ERD) is heterogeneous in both phenotypes and endotypes. Due to insufficient head-to-head comparison studies, it is hard to decide which biological to initiate. This study aimed to compare the efficacy of omalizumab and mepolizumab which can be used in the treatment of patients with severe eosinophilic asthma diagnosed with N-ERD., Methods: The population of this observational, cross-sectional study comprised of N-ERD patients who received omalizumab or mepolizumab for at least 6 months for severe asthma. Outcomes included the asthma control test (ACT), and sino-nasal outcome test scores (SNOT-22), blood eosinophil counts at initiation of biological treatment (T0, baseline) and at the end of 6th months (T6). Adverse effects related to biological treatment and changes of oral corticosteroids dose was recorded., Results: The study included a total of 22 patients, of whom 11 received mepolizumab and 11 received omalizumab. The change in ACT, SNOT-22, eosinophil counts, and adverse effects related to biologicals were similar at T6 (p = 0.606, p = 0.168, p = 0.05, p = 0.053, respectively). However, when examining the SNOT-22 and ACT based on the cumulative distribution curve (SUCRA), mepolizumab (SUCRA value: 0.61, 0.72, respectively) demonstrated greater efficacy compared to omalizumab (SUCRA value: 0.19, 0.35, respectively). The oral corticosteroids discontinuation rate was similar between the two groups (p = 0.05)., Conclusion: We found both omalizumab and mepolizumab to be effective in treatment; however, we determined that mepolizumab may have a potential superiority in efficacy., (© 2024 S. Karger AG, Basel.)

The introduction of biological drugs for the treatment of severe allergic asthma in children, almost twenty years ago, had a substantial impact on both the pathology's clinical course and the quality of life of the patients who receive treatment. Over the years, several molecules have been developed that inhibit molecular targets involved in the pathogenesis of the asthmatic disease. Biological drugs demonstrate a significant improvement in several key clinical parameters in patients with severe asthma. In this review, we provide a concise summary of the evidence on biological therapy for children and adolescents with severe asthma., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Introduction: Severe asthma is characterized by frequent recurrent airway symptoms and exacerbations, and these affect the quality of life. Biological agents can be used in the treatment of patients with severe asthma if the disease cannot be controlled with standard controller treatment. The aim of this study was to compare the clinical characteristics and laboratory data of patients with severe asthma who were switched from omalizumab to mepolizumab and patients with severe asthma who responded to omalizumab., Methods: The clinical characteristics and laboratory data of patients with severe asthma who responded to omalizumab and switched from omalizumab to mepolizumab were compared retrospectively., Results: Evaluation was made of a total of 79 patients, including 64 omalizumab responders and 15 who switched to mepolizumab from omalizumab. After omalizumab and mepolizumab treatment, the annual number of asthma attacks, the use of oral corticosteroid (OCS), the annual number of hospitalizations, and the eosinophil count significantly decreased (omalizumab: p &lt; 0.001, p &lt; 0.001, p &lt; 0.001, p &lt; 0.001, respectively; mepolizumab: p = 0.001, p = 0.001, p = 0.002, p = 0.001, respectively). After omalizumab treatment, the increase in forced expiratory volume in 1 s (FEV1) (%) and asthma control test (ACT) score were determined to be statistically significant (p &lt; 0.001, p &lt; 0.001, respectively). After mepolizumab treatment, the increase in ACT score was significant (p = 0.003). Drug allergy, chronic sinusitis with nasal polyps (CRSwNP), regular use of OCS, and high baseline eosinophil count (cells/µL) were associated with poor response to omalizumab treatment (odds ratio [OR] = 7.86, p = 0.003; OR = 52.92, p &lt; 0.001; OR = 10.16, p = 0.004; OR = 0.99, p = 0.004, respectively). House dust mite sensitivity and high baseline FEV1 (%) were associated with good response to omalizumab treatment (OR = 0.29, p = 0.041; OR = 1.06, p = 0.03, respectively). The blood eosinophil count had diagnostic value in predicting the nonresponsiveness to omalizumab treatment (area under the curve [AUC]: 0.967, p &lt; 0.001, cut-off: 510)., Conclusion: A high pretreatment eosinophil count, concomitant CRSwNP, a history of drug allergy, and regular OCS use may be associated with poor response to omalizumab treatment in patients with severe asthma. Depending on the treatment response, treatment switching can be applied between biological agents. The results of the current study should be supported by multicenter studies., (© 2023 S. Karger AG, Basel.)

Background: Biologics are increasingly being used in patients with severe uncontrolled asthma. However, the trends in their use for treating severe asthma in Japan remain unclear., Methods: The number of patients with asthma prescribed omalizumab or mepolizumab between April 2017 and March 2018 was estimated according to sex, age, and geographical region using data from the National Database of Health Insurance Claims and Specific Health Checkups of Japan., Results: Overall, 5,014, 3,449 and 7,977 patients were prescribed omalizumab, mepolizumab, or either combination, respectively. The total number of patients prescribed biologics displayed a bimodal distribution with peaks in their early teens and seventies. Biologics were most commonly used by male and female patients in their seventies. Prescription was 1.24 times higher in males than in females up to the teenage years, whereas it was 1.95 times higher in females than in males from their twenties onwards. Omalizumab was prescribed 1.45 times more frequently than mepolizumab, especially in pediatric patients, and was prescribed 1.96 times more often to female patients than to male patients. Regional differences were observed in the proportion of patients prescribed biologics. Correlation analysis suggested a weak relationship (r = 0.3226, p = 0.0270) between the proportion of patients prescribed biologics and board-certified allergists according to the geographic region., Conclusions: In Japan, biologics are prescribed more often to older patients with severe asthma compared to those in other countries. Thus, eliminating the regional disparities in asthma treatment by specialists is necessary to provide appropriate medical care to patients with severe asthma., Competing Interests: Declaration of competing interest YN received consulting fees and an honorarium for speakers bureaus from Novo Nordisk, Daiichi Sankyo, and Sanofi. TM received consulting fees from the Health Insurance Claims Review & Reimbursement services. HM received a research grant from GlaxoSmithKline Japan that was unrelated to the submitted work. TIno received a research grant from Johnson & Johnson Vision Care, SEED Co., Ltd., Novartis Pharma K·K., and Kowa Company, Ltd that was unrelated to the submitted work, consulting fees from Santen Pharmaceutical Co., Ltd. and InnoJin, Inc., and stock or stock options from InnoJin, Inc. MF received an honorarium for speakers bureaus from Sanofi K·K., Kyorin Pharmaceutical Co., Ltd., and Novartis Pharma Co., Ltd. The other authors have no conflicts of interest., (Copyright © 2023. Published by Elsevier B.V.)

Background: Evaluation of biologic therapy response is vital to monitor its effectiveness. Authors have proposed various response criteria including good responder, super-responder, non-responder, and clinical remission., Objectives: To ascertain the prevalence of response and clinical remission after long-term treatment (>6 months) of anti-IgE and anti-IL-5/IL-5Rα biologics, compare these results with existing criteria, and identify predictors for non-responders and clinical remission., Methods: A multicenter, real-life study involving severe asthma patients in Spain. Various outcomes were assessed to gauge response and clinical remission against established criteria., Results: The study included 429 patients, 209 (48.7%) omalizumab, 112 (26.1%) mepolizumab, 19 (4.4%) reslizumab and 89 (20.7%) benralizumab, with a mean treatment duration of 55.3±38.8 months. In the final year of treatment, 218 (50.8%) were super-responders, 173 (40.3%) responders, 38 (8.9%) non-responders, and clinical remission in 116 (27%), without differences among biologics. The short-term non-responders (<6 months) were 25/545 (4.6%). Substantial variations in response and clinical remission were observed when applying different published criteria. Predictors of non-response included higher BMI (OR:1.14; 95% CI:1.06-1.23; p<0.001), admissions at ICU (2.69; 1.30-5.56; p=0.01), high count of SAE (1.21; 1.03-1.42; p=0.02) before biologic treatment. High FEV 1 % (0.96; 0.95-0.98; p<0.001), a high ACT score (0.93; 0.88-0.99; p=0.01) before biologic treatment or NSAID-ERD (0.52; 0.29-0.91; p=0.02) showed strong associations with achieving clinical remission., Conclusion: A substantial proportion of severe asthma patients treated long-term with omalizumab or anti-IL5/IL-5Rα achieved a good response. Differences in response criteria highlight the need for harmonization in defining response and clinical remission in biologic therapy to enable meaningful cross-study comparisons., (Copyright © 2023 SEPAR. Published by Elsevier España, S.L.U. All rights reserved.)

Background: With the rise of targeted treatments for asthma, treatment with omalizumab is a new option., Objectives: To assess the improvement of pulmonary function with additional omalizumab treatment in patients (⩾6 years old) with moderate-to-severe allergic asthma., Data Sources and Methods: Observational studies of randomized controlled trials of add-on omalizumab for the treatment of patients with moderate-to-severe allergic asthma, published from the establishment till August 2022, were retrieved from WAN FANG DATA, PubMed, CNKI, Embase, Cochrane, and Web of Science databases. Data extraction and quality evaluation were performed on the literature that met the inclusion criteria, using RevMan 5.3 to analyze the data., Results: A total of 11 randomized controlled clinical trials were included, involving a total of 3578 patients with asthma, 1856 patients in the omalizumab group, and 1722 patients in the control group. The improvement in Forced expiratory volume in 1 s as a percentage of predicted normal and Forced expiratory volume in 1 s was more pronounced in the omalizumab-treated group [MD = 3.91, 95% confidence interval (CI): 1.89-5.94, p  = 0.0002; MD = 0.09, 95% CI: 0.05-0.13, p  < 0.0001], while the improvement in Morning Peak expiratory flow rate was not statistically different between the two groups (MD = 3.64, 95% CI: -22.17-29.45, p  = 0.78)., Conclusion: Additional omalizumab treatment showed some improvement in lung function in patients with moderate-to-severe asthma., Trial Registration: PROSPERO ID:CRD42022378498.

Summary: Background. Allergic bronchopulmonary aspergillosis (ABPA) is an endotype of severe asthma which frequently needs biologics for their steroid sparing effect. We aimed to evaluate the outcomes of reducing the omalizumab dose in patients with ABPA who were on long-term omalizumab treatment. Methods. Once asthma was controlled, two approaches were used to reduce total monthly omalizumab dose: 1) both extending dose intervals from 2 to 4 weeks and decrease omalizumab dose, 2) to reduce omalizumab dose while keeping dose intervals stable. Results. Thirteen patients with ABPA (8F/5M, mean age 53.4 ± 13.0 years) were included. Pre-omalizumab, mean numbers of attacks and hospitalizations were 2.5 ± 1.5 and 1.3 ± 0.8, mean oral corticosteroid (OCS, as methylprednisolone) dose was 12.2 ± 10.4 mg daily. First omalizumab dose reduction was made to all patients at a median time of 35 months (min 13, max 47). The 2 nd dose reduction was made in four patients at median of 23.5 months. Mean OCS decreased to 0.69 ± 0.95 mg/day (p = 0.001) in the 1st year of omalizumab, could be stopped in 11 patients in last evaluation. Attacks/hospitalizations decreased significantly to 0.31 ± 0.86 and 0, respectively, in the 1st year of omalizumab. Total omalizumab dose was reduced by median 40% (min 20, max 60) in 1st intervention and 50% (min 20, max 67) after 2nd intervention. After omalizumab dose reduction, asthma control did not deteriorate and there was no need to increase the omalizumab or OCS-dose. Conclusions. Decreasing the total omalizumab dose does not cause clinical deterioration in ABPA after the disease is controlled.

Introduction: Asthma is a global health problem, with alarming prevalence and mortality rates. Biologic therapies, particularly monoclonal antibodies such as omalizumab, have emerged as promising alternatives, targeting specific immune pathways. This article assesses the efficacy of these biologics in asthma management and attempts to reveal factors associated with their response and failure dynamics., Area Covered: This article explores the efficacy of biologics in asthma, biomarkers, and the relationship between asthma phenotypes (including eosinophilic and non-eosinophilic (neutrophilic) types) and biologic treatments; particularly their effectiveness for each subtype., Expert Opinion: Personalized asthma management that incorporates molecular insights as well as individual variations is of outmost necessity. An emphasis is put on immunological profiling, understanding comorbidities and considering individual patient factors when managing asthma. Cutting-edge phenotyping tools including omic technologies play a crucial role in improving asthma management precision. Variability in patient responses to biologic treatments such as non-responders, partial responders and super responders poses a formidable challenge to effective asthma care management strategies.

Introduction: Biomarkers are needed to inform the choice of biologic therapy in patients with asthma given the increasing number of biologics. We aimed to identify proteins associated with response to omalizumab and mepolizumab., Methods: Aptamer-based proteomic profiling (SomaScan) was used to assess 1437 proteins from 51 patients with moderate to severe asthma who received omalizumab (n = 29) or mepolizumab (n = 22). Response was defined as the change in asthma-related exacerbations in the 12 months following therapy initiation. All models were adjusted for age, sex, and pre-treatment exacerbation rate. Additionally, body mass index was included in the omalizumab model and eosinophil count in the mepolizumab model. We evaluated the association between molecular signatures and response using negative binomial regression correcting for the false discovery rate (FDR) and gene set enrichment analyses (GSEA) to identify associated pathways., Results: Over two-thirds of patients were female. The average age for omalizumab patients was 42 years and 57 years for mepolizumab. At baseline, the average exacerbation rate was 1.5/year for omalizumab and 2.4/year for mepolizumab. Lower levels of LOXL2 (unadjusted p: 1.93 × 10E-05, FDR-corrected: 0.028) and myostatin (unadjusted: 3.87 × 10E-05, FDR-corrected: 0.028) were associated with better response to mepolizumab. Higher levels of CD9 antigen (unadjusted: 5.30 × 10E-07, FDR-corrected: 0.0006) and MUC1 (unadjusted: 1.15 × 10E-06, FDR-corrected: 0.0006) were associated with better response to omalizumab, and LTB4R (unadjusted: 1.12 × 10E-06, FDR-corrected: 0.0006) with worse response. Protein-protein interaction network modeling showed an enrichment of the TNF- and NF-kB signaling pathways for patients treated with mepolizumab and multiple pathways involving MAPK, including the FcER1 pathway, for patients treated with omalizumab., Conclusions: This study provides novel fundamental data on proteins associated with response to mepolizumab or omalizumab in severe asthma and warrants further validation as potential biomarkers for therapy selection., (© 2023. The Author(s).)

Background: A significant breakthrough has been made in treating severe asthma, with the recognition of various asthma phenotypes and an updated management guideline. Type 2 targeted therapies, such as benralizumab and omalizumab; have been identified as an effective treatment for severe asthma, improving patient response, lung function tests and asthma symptom control. This study aimed to evaluate factors contributing to poor response to therapy., Methods: A retrospective single-center cohort study of 162 patients with severe asthma who started biologic therapy; their data were retrieved from medical records for further analysis. Poor responders were patients remained clinically and functionally uncontrolled despite even after augmenting all treatment options., Results: Childhood-onset asthma, bronchiectasis, poor symptom control (ACT below 19), severe airway obstruction (< 60% predicted), and maintenance oral corticosteroid (mOCS) use were significantly associated with poor response to omalizumab and benralizumab; p = 0.0.4 and 0.01; 0.003 and 0.01; 0.01 and 0.001, 0.05 and 0.04; 0.006 and 0.02, respectively. However, chronic rhinosinusitis and IgE < 220kIU/L were associated with higher poor response rates to omalizumab (p = 0.01 and 0.04, respectively). At the same time, female patients and those with blood eosinophils level < 500 cells/mm3 had a higher poor response rate to benralizumab (p = 0.02 and 0.01, respectively). Ischemic heart disease (IHD), bronchiectasis, and continued use of OCS increased the likelihood of poor response to omalizumab by 21, 7, and 24 times (p = 0.004, 0.008, and 0.004, respectively). In contrast, the female gender, childhood-onset asthma and higher BMI increased the likelihood of poor response to benralizumab by 7, 7 and 2 times more, p = 0.03, 0.02 and 0.05, respectively., Conclusion: Poor response to omalizumab treatment was independently associated with ischemic heart disease (IHD), bronchiectasis, and a history of maintenance oral corticosteroid (mOCS) use. Conversely, poor response to benralizumab therapy was independently linked to female gender, childhood-onset asthma and higher body mass index (BMI)., (© 2023. The Author(s).)

Introduction: Refractory status asthmaticus (RSA) is a severe, life-threatening form of asthma exacerbation that persists despite aggressive treatment with systemic corticosteroids, bronchodilators, and other supportive measures. Omalizumab, a monoclonal antibody that targets IgE, has been approved for treating severe allergic asthma and is effective in reducing the frequency of exacerbations and improving asthma control. Limited evidence exists regarding the use of Omalizumab in RSA, but some studies have suggested that it may have a role in its management., Case: A 39-year-old male with a decade-long history of asthma presented to the emergency department intubated and unresponsive to pharmacological therapy. The patient's IgE levels were elevated, and Omalizumab was administered after a comprehensive evaluation. The patient made a dramatic recovery and was successfully weaned off the ventilator within 24 h of receiving Omalizumab. He made an uneventful recovery and was discharged home on Omalizumab once every two weeks with regular follow-ups., Discussion and Conclusion: Per our literature search, only 3 cases have been reported where Omalizumab was administered to patients with RSA to wean them off ventilatory support successfully. This case study adds to the existing data on the potential benefits of Omalizumab in managing RSA. It suggests it may be a valuable treatment option for patients who do not respond to standard therapy. However, further research is needed to determine the efficacy and safety of Omalizumab in this population.

Patients with uncontrolled, allergic severe asthma may be prescribed biologic therapies to reduce exacerbations and improve disease control. Randomized controlled trials (RCTs) of these therapies have differed in design, with varying results overall and by baseline blood eosinophil count (BEC). This study describes published annualized asthma exacerbation rate (AAER) reductions from RCTs in patients with allergic severe asthma, overall and by baseline BEC category. A literature search was performed to identify published phase 3 RCT data of US Food and Drug Administration-approved biologics for severe asthma in patients with severe, uncontrolled asthma and confirmed sensitization to perennial aeroallergens. Analyses focused on AAER reduction versus placebo in the overall population and/or in those with an elevated or low BEC at baseline or screening. Baseline serum total immunoglobulin E levels varied between RCT populations. In patients with allergic severe asthma across all BEC categories, data were available for tezepelumab, dupilumab, benralizumab and omalizumab only; the greatest AAER reduction was observed with tezepelumab. In patients with allergic severe asthma and BECs of ≥ 260 cells/µL or ≥ 300 cells/μL, AAER reductions were observed with all biologics (tezepelumab, dupilumab, mepolizumab, benralizumab and omalizumab); the greatest AAER reduction was observed with tezepelumab and the smallest AAER reduction was observed with omalizumab. In patients with allergic severe asthma and BECs of < 260 cells/µL or < 300 cells/μL (regardless of historical BEC), an AAER reduction was observed with tezepelumab but not with benralizumab or omalizumab. Differential mechanisms of action may explain the differences in results observed between biologics. Among patients with allergic severe asthma, the efficacy of biologics in RCTs varied considerably overall and by BEC. Tezepelumab was the only biologic to demonstrate AAER reductions consistently across all subgroups. These differences can inform provider treatment decisions when selecting biologic treatments for patients with allergic severe asthma., (© 2023. The Author(s).)

Background: Patient adherence to biologic therapies is crucial for clinical benefits. Previous assessments of US patient adherence to severe asthma (SA) biologic therapies have relied on health care insurance claims data that have limitations., Objective: To describe real-world, specialist-reported, biologic administration and adherence among US adults with SA., Methods: CHRONICLE (ClinicalTrials.gov identifier: NCT03373045) is an ongoing real-world, noninterventional study of patients with SA treated by US subspecialists. Sites report date and location for all biologic administrations. We evaluated biologic (benralizumab, dupilumab, mepolizumab, omalizumab, reslizumab) adherence as the proportion of days covered (PDC) during the first 52 weeks and the mean number of days until patients received the expected number of doses for 13, 26, and 52 weeks of treatment., Results: A total of 2117 patients received biologic administrations between February 2018 and February 2022. Most patients (84%) received biologic administrations at a subspecialist site. Over time, administrations at specialist sites decreased, whereas at-home administrations increased. The median PDC was 87%; the mean number of days to receive a 52-week (364-day) equivalent number of doses was 423 for all biologics (average delay of 58 days). Dupilumab had the lowest PDC and highest mean delays in dosing across all intervals; better adherence was observed among commercially insured patients., Conclusion: Patients with SA are mostly adherent to biologic therapies. Biologics with shorter dosing intervals and at-home administration had worse adherence, likely because of greater opportunities for delays. Specialist-reported administration data provide a unique perspective on biologic adherence, which may be overestimated for at-home administrations by insurance claims data., Clinical Trial Registration: ClinicalTrials.gov: NCT03373045., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

In obese severe asthmatics, the degree of type 2 inflammation may vary according to their atopic status and past smoking history. In this study, we aimed to analyze the clinical and physiopathological features of obese and nonobese severe asthmatics treated with omalizumab or mepolizumab treatment. In addition we aimed to compare the clinical, spirometric outcomes and total peripheral eosinophilic count (TEC) changes after treatment with these 2 biologic agents in obese and nonobese groups. In this retrospective, cross sectional study, 121 severe asthmatic treated with biologic agents (omalizumab = 88 or mepolizumab = 33) for at least 16 weeks were included. Obese (n: 44) and nonobese severe asthmatics (n: 77) were analyzed according to whether they provided a ≥ 10 pack/years (p/y) or <10 p/y smoking history and were found to be atopic. Obese and nonobese groups were compared in terms of the change in the asthma control test, asthma attacks, TEC, and forced expiratory volume in the first second (FEV1) after treatment. In patients with ≥10 p/y smoking history, nonobese group had a significantly higher TEC compared to obese group [median (min-max) 660 cells/μL (200-1500) vs 300 cells/μL (110-770); p: 0.013]. Within the nonobese group, nonatopic patients had a significantly higher TEC compared to atopic patients [median (min-max) 1200 cells/μL (100-2100) vs 310 cells/μL (0-2730); p: 0.021]. Both biologic agents had similar effects on improving asthma control test and in reducing asthma attacks; however, mepolizumab was more effective in suppressing TEC. The improvement in FEV1 in obese group following biologic 2 agents was very similar but in nonobese group, mepolizumab was found to be superior (510 mL vs. 295 mL; p: 0.034). In our real-life study, nonobese severe asthmatics with ≥10 p/y smoking history and those that were nonatopic had higher TEC. Compared to omalizumab, mepolizumab was superior at reducing TEC in all asthmatics and in improving FEV1 in nonobese group., Competing Interests: All authors have no conflict of interest., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

This paper aims to review biologics in allergic rhinitis (AR). Biologic agents of Omalizumab, Dupilumab, Mepolizumab, Reslizumab, and Benralizumab are reviewed in detail. The search is performed in "Pubmed," "Google," Google Scholar" and EBSCO Academic Search Ultimate (EKUAL) database of Kırıkkale University Library from 2021 to 2000, and randomized and/or placebo-controlled studies, review papers, meta-analysis, and reports are taken into consideration. The search was performed with the keywords of "allergic rhinitis," "biologics," "biologic agents," "Omalizumab," "Dupilumab," "Mepolizumab," "Reslizumab," "Benralizumab," "Anti IgE," "Anti-IL-4/IL-13", "Anti IL-5". Search is also performed in the "U.S. Food and Drug Administration" (FDA) and "European Medicines Agency" (EMA) web systems. Biological agents such as monoclonal antibodies (MAb) in treatment are called biological therapy or biotherapy. Omalizumab is a humanized Anti-IgE monoclonal antibody. Omalizumab treatment improved the Daily Nasal Rescue Medication Score (DNSSS) and decreased the use of antiallergic drugs in seasonal and perennial AR and rhino-conjunctivitis. Omalizumab is also used in specific immunotherapy patients with allergic rhinitis and reduced allergic reactions associated with allergen immunotherapy, such as anaphylaxis. Dupilumab is an Anti-IL-4/IL-13 biologic agent. Dupilumab treatment significantly improved sino-nasal Outcome Test (SNOT-22) total scores in perennial allergic rhinitis. Anti-IL-5 monoclonal antibodies of Mepolizumab, Reslizumab Benralizumab reduce the number of eosinophils in the blood and tissue, corticosteroid addiction and asthma attacks are reduced, and their use in the treatment of severe eosinophilic asthma has been approved. Biologics, especially Omalizumab, and Dupilumab, may be used more in allergic rhinitis.

Introduction: Omalizumab is used for the treatment of severe allergic asthma., Objective: The aim of this study was to evaluate the clinical features and laboratory data of patients with severe allergic asthma classified as super-responder or non super-responder to omalizumab., Methods: Comparisons were made of the laboratory data and clinical features of patients with severe allergic asthma. Patients who had no asthma exacerbation, no oral corticosteroid (OCS) use, asthma control test (ACT) score >20 and forced expiratory volume in 1 s (FEV1) >80% were considered super-responder after omalizumab., Results: A total of 90 patients were included in the study, comprising 19 (21.1%) males. The age at onset of asthma, allergic rhinitis rate, number of endoscopic sinus surgeries (ESS), intranasal corticosteroid (INS) use, baseline FEV 1 (%) and ACT score were significantly higher in the omalizumab super-responder group ( p  = 0.013, p  = 0.015, p  = 0.002, p  = 0.001, p  = 0.001 and p  < 0.001, respectively). The duration of asthma, rate of Chronic Rhinosinusitis with Nasal Polyps (CRSwNP), regular use of OCS, baseline eosinophil count and eosinophil-to-lymphocyte ratio were significantly higher in the omalizumab non super-responder group ( p  = 0.015, p  < 0.001, p  = 0.004, p  < 0.001 and p  < 0.001, respectively). Blood eosinophil count (AUC: 0.187, p  < 0.001), eosinophil-to-lymphocyte ratio (AUC: 0.150, p  < 0.001) and FEV1 (%) (AUC:0.779, p  = 0.001) were determined to have diagnostic value in predicting the treatment response to omalizumab of patients with severe allergic asthma., Conclusion: High-blood eosinophil levels, CRSwNP and low pretreatment lung capacity may affect omalizumab treatment response in patients with severe allergic asthma. These results should be supported by further multicenter real-life studies.