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Allergy Dec 2023Autoimmunity is the break of tolerance to self-antigens that leads to organ-specific or systemic diseases often characterized by the presence of pathogenic autoreactive... (Review)
Review
Autoimmunity is the break of tolerance to self-antigens that leads to organ-specific or systemic diseases often characterized by the presence of pathogenic autoreactive antibodies (AAb) produced by plasmablast and/or plasma cells. AAb are prevalent in the general population and not systematically associated with clinical symptoms. In contrast, in some individuals, these AAb are pathogenic and drive the development of signs and symptoms of antibody-mediated autoimmune diseases (AbAID). AAb production, isotype profiles, and glycosylations are promoted by pro-inflammatory triggers linked to genetic, environmental, and hormonal parameters. Recent evidence supports a role for pathogenic AAb of the IgE isotype in a number of AbAID. Autoreactive IgE can drive the activation of mast cells, basophils, and other types of FcεRI-bearing cells and may play a role in promoting autoantibody production and other pro-inflammatory pathways. In this review, we discuss the current knowledge on the pathogenicity of autoreactive IgE in AbAID and their status as therapeutic targets. We also highlight unresolved issues including the need for assays that reproducibly quantify IgE AAbs, to validate their diagnostic and prognostic value, and to further study their pathophysiological contributions to AbAID.
Topics: Humans; Immunoglobulin E; Autoimmune Diseases; Basophils; Omalizumab; Autoimmunity; Receptors, IgE
PubMed: 37555488
DOI: 10.1111/all.15843 -
The Journal of Allergy and Clinical... Mar 2024The landscape of food allergy (FA) treatment is poised for a paradigm shift with the emergence of biologic therapies. The Food and Drug Administration approval of a...
The landscape of food allergy (FA) treatment is poised for a paradigm shift with the emergence of biologic therapies. The Food and Drug Administration approval of a standardized peanut powder for oral immunotherapy in 2020 marked a milestone, signaling a departure from allergen avoidance toward proactive treatment strategies. Although oral immunotherapy has been proven effective in desensitizing patients to specific allergens, there are several limitations such as lacking standardization, a long-time commitment to achieve maintenance, and adverse events. Biologics, including omalizumab, dupilumab, and antialarmins, have shown promise in treating various allergic diseases, including FA. These biologics target the underlying immunologic pathways driving allergic reactions, offering an antigen-agnostic approach. Omalizumab (anti-IgE) has been the most studied biologic in this space and can be used both as an adjunct therapy with oral immunotherapy and as monotherapy. Dupilumab targeting IL-4 and IL-13 also shows promise as an adjunct therapy. The emergence of antialarmins further broadens the spectrum of FA treatment possibilities. Biologics represent a transformative approach to FA treatment, directly addressing the underlying mechanisms. Future research should focus on patient selection criteria, personalized biomarker panels, optimal timing of intervention, and treatment durations.
Topics: Humans; Omalizumab; Desensitization, Immunologic; Food Hypersensitivity; Food; Allergens; Biological Products; Administration, Oral
PubMed: 38013157
DOI: 10.1016/j.jaip.2023.11.032 -
Respirology (Carlton, Vic.) Aug 2023Type 2 (T2) innate lymphoid cells (ILC2s) contribute to airway inflammation and disease in asthma. We hypothesize that ILC2s isolated from people with severe allergic...
BACKGROUND AND OBJECTIVE
Type 2 (T2) innate lymphoid cells (ILC2s) contribute to airway inflammation and disease in asthma. We hypothesize that ILC2s isolated from people with severe allergic and eosinophilic asthma would exhibit an enhanced T2 inflammatory activity that would be altered following treatment with mepolizumab and omalizumab. We compare peripheral blood (PB) isolated ILC2's proliferative capacity, IL-5 and IL-13 secretion and phenotype between healthy without asthma (HC), non-asthma allergic (NAA), mild asthma (MA) and severe allergic and eosinophilic asthma (SA) subjects. We then determined the impact of 6 months treatment with either mepolizumab or omalizumab on ILC2s physiology of SA subjects.
METHODS
ILC2s were sorted and cultured in the presence of IL-2, IL-25, IL-33 and thymic stromal lymphopoietin (TSLP) for 14 days. ILC2s proliferation, phenotypes and functions were assessed using flowcytometry. The ILC2s response was then reassessed following clinically successful treatment of SA subjects with mepolizumab and omalizumab.
RESULTS
SA ILC2s demonstrated increased proliferative capacity, TSLP receptor (TSLPR), GATA3 and NFATc1 protein expressions and increased IL-5 and IL-13 release. ILC2s were also capable of releasing IL-6 in response to stimulation. Mepolizumab treatment reduced ILC2s proliferative capacity and expression of TSLPR, GATA3 and NFATc1. Both mepolizumab and omalizumab were associated with reduced ILC2s release of IL-5 and IL-13, only mepolizumab reduced IL-6.
CONCLUSION
ILC2s from severe allergic and eosinophilic asthma demonstrated an active phenotype typified by increased proliferation, TSLPR, GATA3 and NFATc1 expression and increased IL-5, IL-13 and IL-6 release. Mepolizumab reduced markers of ILC2s activation.
Topics: Humans; Immunity, Innate; Interleukin-13; Biological Products; Omalizumab; Interleukin-5; Interleukin-6; Lymphocytes; Asthma; Cytokines; Pulmonary Eosinophilia; Cell Proliferation
PubMed: 37114915
DOI: 10.1111/resp.14506 -
Skinmed 2023Omalizumab is an effective and safe treatment option with licensed doses in patients with chronic spontaneous urticaria (CSU); however, some patients are not responsive...
Omalizumab is an effective and safe treatment option with licensed doses in patients with chronic spontaneous urticaria (CSU); however, some patients are not responsive to licensed doses and require updosing. As studies concerning updosing were insufficient, the present study evaluated the effectiveness and safety of omalizumab updosing (300 mg every 2 weeks) in CSU patients. Data of CSU patients treated with omalizumab were analyzed retrospectively. As an outcome measure, physician assessment of treatment response (complete response [CR], partial response, and unresponsiveness) was used. In all, 49 patients depicting CR to omalizumab 300 mg every 4 weeks and 54 patients treated with omalizumab 300 mg every 2 weeks were included in the study. Mean duration of the disease in updosing group was significantly lengthier than the CR group. The mean percentage level of eosinophils and basophils was significantly higher in the CR group. The history of systemic corticosteroid and oral cyclosporine treatment was significantly more frequent in the updosing group. Treatment with omalizumab 300 mg every 2 weeks for 12 weeks led to CR in 41 patients (75.9%). Our results confirmed the efficacy and safety of omalizumab updosing. Low baso-phil and eosinophil levels could also be important factors in defining the need for updosing.
Topics: Humans; Retrospective Studies; Omalizumab; Chronic Urticaria; Administration, Oral; Cyclosporine
PubMed: 37634098
DOI: No ID Found -
Drugs Aug 2023Data on the clinical efficacy and remodeling of omalizumab therapy in patients on oral corticosteroids (OC) are limited. (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
Data on the clinical efficacy and remodeling of omalizumab therapy in patients on oral corticosteroids (OC) are limited.
OBJECTIVE
The purpose of the study is to show that in patients with corticosteroid-dependent asthma, omalizumab is a corticosteroid-sparing therapy able to inhibit airway remodeling and to reduce disease burden (lung function impairment, exacerbations).
METHODS
This study is a randomised open-label study evaluating the addition of omalizumab to the standard of care in patients with severe asthma receiving oral corticosteroids. The primary endpoint was represented by the change in OC monthly dose by the end of treatment and secondary endpoints included spirometry changes, airway inflammation (FeNO), number of exacerbations and airways remodelling assessed by bronchial biopsies studied by transmission electron microscopy. As a safety variable, adverse effects were recorded.
RESULTS
Efficacy was assessed for 16 patients in the omalizumab group and 13 in the control group. The final cumulative mean monthly OC doses were 34.7 mg and 217 mg for the omalizumab and control group, respectively; the mean difference between groups adjusted for baseline was -148.1 [95% confidence interval (CI) -243.6, -52.5; p = 0.004]. OC withdrawal of 75% versus 7.7% (p = 0.001) was observed in the omalizumab and control group, respectively. Omalizumab provided a slowing of forced expiratory volume in one second (FEV) loss (70 mL versus 260 mL), a significant decrease in FeNO values and a reduction in the annual relative risk of clinically significant exacerbations of 54%. The treatment was well tolerated. The morphological study showed a significant decrease in basement membrane thickness in the omalizumab group (6.7 µm versus 4.6 µm) compared with controls (6.9 µm versus 7 µm) [mean difference between groups adjusted for baseline was -2.4 (95% CI -3.7, -1.2; p < 0.001], as well as a decrease in intercellular spaces (1.18 µm versus 0.62 µm and 1.21 µm versus 1.20 µm, p = 0.011, respectively). A qualitative improvement was also observed in the treated group.
CONCLUSIONS
Omalizumab showed a marked OC-sparing capacity and was associated with an improvement in clinical management that correlated with bronchial epithelial repair. In OC-dependent asthma, reversibility of remodelling is possible; the concepts that basement membrane enlargement is detrimental and that chronic airway obstruction is systematically irreversible are outdated (EudraCT: 2009-010914-31).
Topics: Humans; Adrenal Cortex Hormones; Anti-Asthmatic Agents; Asthma; Omalizumab; Respiratory Function Tests; Treatment Outcome
PubMed: 37436680
DOI: 10.1007/s40265-023-01905-5 -
Revue Des Maladies Respiratoires Oct 2023Severe asthma in children remains relatively rare. It is no longer considered as a single disease but rather as a syndrome corresponding to different phenotypes and... (Review)
Review
INTRODUCTION
Severe asthma in children remains relatively rare. It is no longer considered as a single disease but rather as a syndrome corresponding to different phenotypes and distinct pathophysiological pathways. Various biomarkers can contribute to phenotyping, essentially specific IgE test results, blood eosinophil counts, the exhaled fraction of NO (FeNO) assay, as well as deep lung biomarkers from induced sputum, bronchoalveolar lavage or bronchial biopsy.
STATE OF KNOWLEDGE
In children, the biologics currently approved for severe asthma are omalizumab, mepolizumab and dupilumab from the age of 6, and tezepelumab from the age of 12.
PERSPECTIVES
Benralizumab and tezepelumab offer promising perspectives and a pediatric extension could be of interest in future treatment of severe pediatric asthma.
CONCLUSIONS
Based on physiopathological mechanisms, biologics represent a new and promising approach in the treatment of asthma. That said, the long-term efficacy and impact of these treatments on the natural history of the disease require further investigation. It is of paramount importance to take into account the specificities of pediatric asthma and, more particularly, to conduct clinical trials in younger patients.
PubMed: 37749027
DOI: 10.1016/j.rmr.2023.09.002 -
The Journal of Asthma : Official... Jan 2024Modification of the immune system with biologics raises theoretical concerns about the risk of infections but it is still unclear whether currently routinely used...
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.
PubMed: 38294705
DOI: 10.1080/02770903.2024.2311236 -
Viruses Jul 2023Since more than a century ago, there has been awareness of the connection between viral infections and the onset and exacerbation of urticaria. Our knowledge about the... (Review)
Review
Since more than a century ago, there has been awareness of the connection between viral infections and the onset and exacerbation of urticaria. Our knowledge about the role of viral infection and vaccination in acute and chronic urticaria improved as a result of the COVID-19 pandemic but it has also highlighted knowledge gaps. Viral infections, especially respiratory tract infections like COVID-19, can trigger the onset of acute urticaria (AU) and the exacerbation of chronic urticaria (CU). Less frequently, vaccination against viruses including SARS-CoV-2 can also lead to new onset urticaria as well as worsening of CU in minority. Here, with a particular focus on COVID-19, we review what is known about the role of viral infections and vaccinations as triggers and causes of acute and chronic urticaria. We also discuss possible mechanistic pathways and outline the unmet needs in our knowledge. Although the underlying mechanisms are not clearly understood, it is believed that viral signals, medications, and stress can activate skin mast cells (MCs). Further studies are needed to fully understand the relevance of viral infections and vaccinations in acute and chronic urticaria and to better clarify causal pathways.
Topics: Humans; COVID-19; Angioedema; Pandemics; SARS-CoV-2; Urticaria; Chronic Urticaria; Vaccination
PubMed: 37515272
DOI: 10.3390/v15071585 -
Journal of Investigational Allergology... Dec 2023Impairment of smell is more commonly related to chronic rhinosinusitis with nasal polyps (CRSwNP) than without, especially when asthma and/or NSAID-exacerbated... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Impairment of smell is more commonly related to chronic rhinosinusitis with nasal polyps (CRSwNP) than without, especially when asthma and/or NSAID-exacerbated respiratory disease and type 2 inflammation are also present. Therapeutic options include intranasal and systemic corticosteroids, surgery, and, more recently, biological therapy. We summarize current knowledge on the effect of biologics on olfaction in patients with CRSwNP.
METHODS
We performed a systematic search of the PubMed and Cochrane databases from January 2001 to June 2022. The inclusion criteria were as follows: adult patients with CRS treated with dupilumab, omalizumab, mepolizumab, benralizumab, or reslizumab; and studies published in English reporting outcomes for sense of smell based on psychophysical and/or subjective tools. We excluded reports that did not assess CRSwNP, loss of smell evaluated with a method other than those accepted in the inclusion criteria, review articles, and expert opinions. No funding was received.
RESULTS
Dupilumab has demonstrated rapid and sustained long-term improvement in smell in clinical trials and in real life. Omalizumab improves smell at 24 weeks. This improvement is maintained in the long-term, although it is not clinically relevant. Mepolizumab and benralizumab improved smell in the long term based on a subjective scale. No studies examining the improvement in smell in patients with CRSwNP treated with reslizumab were found. Indirect comparisons by meta-analysis consistently conclude that dupilumab is the most effective biologic for improving impaired sense of smell.
CONCLUSION
Dupilumab seems to be more efficacious for improving the sense of smell than omalizumab, mepolizumab, and benralizumab.
Topics: Adult; Humans; Antibodies, Monoclonal; Nasal Polyps; Omalizumab; Smell; Rhinosinusitis; Chronic Disease; Sinusitis; Rhinitis; Quality of Life
PubMed: 37669083
DOI: 10.18176/jiaci.0939 -
Current Opinion in Allergy and Clinical... Oct 2023The purpose of this review is to provide an overview of the recent advancements and relevance of the autoimmune theories in chronic spontaneous urticaria (CSU). (Review)
Review
PURPOSE OF REVIEW
The purpose of this review is to provide an overview of the recent advancements and relevance of the autoimmune theories in chronic spontaneous urticaria (CSU).
RECENT FINDINGS
Two primary types of autoimmunity, Type I and Type IIb, have emerged as major contributors to CSU, characterized by immunoglobulin E (IgE) and immunoglobulin G (IgG) autoantibodies, respectively. Genetic evidence supports the notion that CSU shares more similarities with other autoimmune diseases rather than atopic diseases. Novel autoallergens such as FcεRI and tissue transglutaminase have been identified, contributed to our understanding of autoimmune mechanisms. Furthermore, the potential overlap between Type I and Type IIb autoimmunity has been recognized. Evaluating the autoimmune status of CSU patients through biomarkers and understanding their clinical implications is vital for effective management. For instance, CSU patients with Type IIb autoimmunity, with or without coexisting Type I autoimmunity, may exhibit resistance to H1-antihistamines and omalizumab treatment but could potentially respond well to cyclosporine or Bruton's tyrosine kinase inhibitors.
SUMMARY
Further investigations are needed to explore new autoallergens and autoantibodies in CSU, establishing their connection to the development of autoimmunity. The efficacy of novel drugs targeting different mechanisms should be examined to determine their responses in both autoimmune CSU and nonautoimmunity-related CSU.
Topics: Humans; Autoimmunity; Urticaria; Chronic Disease; Chronic Urticaria; Autoimmune Diseases; Autoantibodies; Omalizumab
PubMed: 37459281
DOI: 10.1097/ACI.0000000000000927