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Inflammation Research : Official... Jun 2024In 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... (Review)
Review
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.
PubMed: 38907743
DOI: 10.1007/s00011-024-01908-2 -
The Journal of Allergy and Clinical... Jun 2024
PubMed: 38906397
DOI: 10.1016/j.jaip.2024.06.014 -
Human Antibodies Jun 2024Asthma is a major global disease affecting adults and children, which can lead to hospitalization and death due to breathing difficulties. Although targeted monoclonal... (Review)
Review
PURPOSE OF THE REVIEW
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.
PubMed: 38905039
DOI: 10.3233/HAB-240002 -
Lung Jun 2024Treatment of allergic bronchopulmonary aspergillosis (ABPA) is challenging. Biological therapies have been reported as adjunctive treatments for ABPA, primarily in case... (Review)
Review
BACKGROUND
Treatment of allergic bronchopulmonary aspergillosis (ABPA) is challenging. Biological therapies have been reported as adjunctive treatments for ABPA, primarily in case series or case reports. This study aimed to analyze the efficacy of biologics for managing ABPA both qualitatively and quantitatively.
METHODS
All articles on APBA published in October 2023 were searched in PubMed, Web of Science, ClinicalTrials.gov, and Embase databases. The effects of interest were the mean changes from baseline for outcomes, including exacerbation rates, oral corticosteroids usage (OCS), and total immunoglobulin E (IgE) levels. Reported outcomes were quantitatively synthesized by usual or individual patient data (IPD) meta-analyses. PROSPERO registration number: CRD42022373396.
RESULTS
A total of 86 studies were included in the systematic review including 346 patients. Sixteen studies on omalizumab were pooled for the usual meta-analysis. Omalizumab therapy significantly reduced exacerbation rates (- 2.29 [95%CI - 3.32, - 1.26]), OCS dosage (- 10.91 mg [95%CI - 18.98, - 2.85]), and total IgE levels (- 273.07 IU/mL [95%CI - 379.30, - 166.84]), meanwhile improving FEV1% predicted (10.09% [95%CI 6.62, 13.55]). Thirty-one studies on dupilumab, mepolizumab, or benralizumab were pooled to perform an IPD meta-analysis, retrospectively. Both dupilumab and mepolizumab significantly reduced exacerbation rates, OCS, and total IgE levels. Benralizumab showed a similar trend, but it was not statistically significant. Tezepelumab showed weak evidence of its effects on ABPA. All five biologics led to milder clinical symptoms (e.g., cough, wheezing) with serious adverse effects that happened once in omalizumab treatment.
CONCLUSION
These results indicate the clinical benefit of omalizumab, dupilumab, and mepolizumab in patients with ABPA. Further randomized, controlled studies with a larger sample size and longer follow-up are needed to confirm these findings.
PubMed: 38898129
DOI: 10.1007/s00408-024-00717-y -
Annals of Allergy, Asthma & Immunology... Jun 2024The development of monoclonal antibodies that selectively target IgE and type 2 immunity has opened new possibilities in the treatment of allergies. Although they have... (Review)
Review
The development of monoclonal antibodies that selectively target IgE and type 2 immunity has opened new possibilities in the treatment of allergies. Although they have been used mainly as single therapies that have shown efficacy in the management of asthma and other T2-mediated diseases, there is a growing interest in using these monoclonal antibodies in combination with allergen immunotherapy (AIT). AIT has transformed the treatment of allergic diseases by aiming to modify the underlying immune response to allergens rather than just providing temporary symptom relief. Despite the proven efficacy and safety of AIT, unmet needs call for further research and innovation. Combination strategies involving biologics and AIT exhibit potential in improving short-term efficacy, reducing adverse events, and increasing immunological tolerance. Anti-IgE emerges as the most promising therapeutic strategy, not only enhancing AIT's safety and tolerability but also providing additional evidence of efficacy compared to AIT alone. Anti-IL-4 receptor offers a reduction in side effects and an improved immunological profile when combined with AIT, however its impact on short-term efficacy appears limited. The combination of cat dander subcutaneous immunotherapy with anti-TSLP was synergistic with enhanced efficacy and altered immune responses that persisted for one year after discontinuation compared to AIT alone. Long-term studies are needed to evaluate the sustained benefits and safety profiles of combination strategies.
PubMed: 38897405
DOI: 10.1016/j.anai.2024.06.016 -
International Archives of Allergy and... Jun 2024Chronic inducible urticaria (CIndU) is a subtype of chronic urticaria (CU), which requires specific triggers to occur. Despite their common occurrence, treatment...
INTRODUCTION
Chronic inducible urticaria (CIndU) is a subtype of chronic urticaria (CU), which requires specific triggers to occur. Despite their common occurrence, treatment response rates and predictors of treatment responses are largely lacking in the literature. This study evaluates antihistamine (AH) and omalizumab response rates in the most common CIndU subtypes and examines whether certain features can predict treatment responses.
METHODS
We retrospectively analyzed CU patients with at least one CIndU subtype and performed comparisons between subgroups, in a total of 423 patients (70% CIndU, 30% chronic spontaneous urticaria [CSU] plus CIndU).
RESULTS
The treatment response rates in CIndU were 51.6%, 51.5%, and 86.5% with standard-dose second-generation H1-antihistamines (sgAHs), updosed/combined sgAH, and omalizumab, respectively. Overall AH response was higher in CIndU than CSU plus CIndU (78.3% vs. 62%, p = 0.002) and in symptomatic dermographism (SD) and cold urticaria (ColdU) than cholinergic urticaria (ChoU) (83.2% vs. 78.3 vs. 60.9%, p = 0.04). AH-refractory patients had a longer disease duration (45.2 ± 56.7 months vs. 37 ± 51.9 months, p = 0.04), more angioedema, accompanying CSU, mixed CIndU subtypes (37.5% vs. 21.1%, p = 0.003; 45.1% vs. 27.1%, p = 0.002; 8.8% vs. 2.4%, p = 0.014), and lower baseline urticaria control test scores (5.86 ± 3.3 vs. 8.6 ± 3.6, p < 0.001) than AH-responsive patients.
CONCLUSION
CIndU exhibits a good response to both AHs and omalizumab. Notably, the response to AHs is more pronounced in SD and ColdU compared to ChoU. Disease duration, angioedema, accompanying CSU, mixed CIndU, and lower baseline UCT scores may be used to predict AH treatment outcome in CIndU.
PubMed: 38889696
DOI: 10.1159/000536579 -
The Journal of Asthma : Official... Jul 2024To evaluate the benefits of combining omalizumab with specific immunotherapy (SCIT) in the treatment of children with bronchial asthma.
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.
PubMed: 38888746
DOI: 10.1080/02770903.2024.2368193 -
Frontiers in Pharmacology 2024We describe the case of a 10-year-old boy with asthma (AS), accompanied by allergic rhinitis (AR), food allergy (FA), and combined attention-deficit/hyperactivity...
Omalizumab in combination with subcutaneous immunotherapy for the treatment of multiple allergies associated with attention-deficit/hyperactivity disorder: a case report and a literature review.
We describe the case of a 10-year-old boy with asthma (AS), accompanied by allergic rhinitis (AR), food allergy (FA), and combined attention-deficit/hyperactivity disorder (ADHD), who was treated at Shanghai Renji Hospital on 11 July 2020. The efficiency of the previous treatment with salmeterol/ticlosone was poor. Treatment with montelukast sodium resulted in development of neurological symptoms. Treatment with omalizumab in combination with subcutaneous immunotherapy (SCIT) was then initiated in our department based on anti-asthmatic therapy. Symptoms of asthma were completely controlled, and FA and AR symptoms improved. The treatment regimen led to a significant improvement in ADHD symptoms and the overall quality of life of the patient. The literature search was done in the PubMed database using "attention deficit/hyperactivity disorder/ADHD" and "asthma" as keywords, and we identified 47 relevant articles. In conclusion, our results show that treating asthma with omalizumab in combination with salmeterol/ticlosone and SCIT is efficient in controlling symptoms of multiple allergies and may lead to the improvement in ADHD symptoms and the overall quality of life of pediatric patients with ADHD. While current studies suggest that allergic diseases are closely related to ADHD, there is still a lack of studies or case reports of complete treatment protocols to provide clinical clues for management of the disease.
PubMed: 38887551
DOI: 10.3389/fphar.2024.1367551 -
Annals of Allergy, Asthma & Immunology... Jun 2024Chronic urticaria can be divided into two subsets: chronic spontaneous urticaria (CSU) with skin lesions occurring without a specific trigger and chronic inducible... (Review)
Review
Chronic urticaria can be divided into two subsets: chronic spontaneous urticaria (CSU) with skin lesions occurring without a specific trigger and chronic inducible urticaria (CIndU) which has an identified specific stimulus. The annual prevalence of CU is 0.5% to 2.3% globally. CSU is a self-limited disorder in most cases, with an average duration of 2 to 5 years, but symptoms persist beyond five years in up to 30% of patients. The first line of treatment is a daily non-sedating, second-generation H1- antihistamines. CSU guidelines recommend using oral non-sedating antihistamines up to 4-fold in patients with CSU unresponsive to standard doses as the next step in treatment. A meta-analysis found that the rate of response in patients with CSU who responded to up-dosing was 63.2%. Therefore, approximately 40% of patients continue to have persistent hives and itching requiring treatment with the biologic omalizumab based on evidence from randomized controlled trials. Although omalizumab has been shown to markedly improve symptoms of CSU, omalizumab is not effective in all patients and has not been shown to induce long-term disease remission. Thus, there is an unmet need for more effective treatments that can lead to cure or long-term remission. In this review, we will provide an overview of new treatment targets and biologics that are under investigation for the treatment of CSU.
PubMed: 38885835
DOI: 10.1016/j.anai.2024.05.020 -
The Journal of Asthma : Official... Jul 2024Specific biomarkers, such as eosinophilia in peripheral blood or fractional exhaled nitric oxide (FeNO), can guide us in the choice of biologic therapy, allowing a more...
BACKGROUND
Specific biomarkers, such as eosinophilia in peripheral blood or fractional exhaled nitric oxide (FeNO), can guide us in the choice of biologic therapy, allowing a more personalized approach. Although there are multiple evidences in the literature about the role of FeNO as a predictor of response to different biologic treatments, there are no data on the relationship between FeNO changes and clinical response to the four biologic drugs currently in use.
OBJECTIVE
To evaluate and to compare the expression of multiple-flows FeNO parameters in a cohort of patients with severe asthma (SA) before and during the treatment with biologics to evaluate the performance of these biomarkers in predicting the achievement of clinical remission.
METHODS
We prospectively enrolled 50 patients with severe asthma eligible for biologic therapy. Patients underwent clinical and functional monitoring at baseline (T0) and after 1, 6, and 12 months of treatment (T1, T6, T12), including multiple flows FeNO assessment.
RESULTS
A statistically significant reduction of FeNO50 values and J'awNO was observed only in benralizumab and dupilumab subgroups. Among biomarkers, the reduction of FeNO 50 values at T1 was associated with a higher probability of achieving clinical remission at T12 ( = 0.003), which was also confirmed by ROC curve analysis (AUC 0.758, = 0.002; sensitivity 60% and specificity 74% for a reduction of 16 ppb).
CONCLUSION
These data confirm the potential of this biomarker in predicting clinical response to biologic treatment in patients with severe asthma in order to guide clinical decisions and evaluate a shift to other biologic therapy.
PubMed: 38884564
DOI: 10.1080/02770903.2024.2370012