-
Allergology International : Official... Apr 2020IgE and mast cells play a pivotal role in various allergic diseases, including asthma, allergic rhinitis, and urticaria. Treatment with omalizumab, a monoclonal anti-IgE... (Review)
Review
IgE and mast cells play a pivotal role in various allergic diseases, including asthma, allergic rhinitis, and urticaria. Treatment with omalizumab, a monoclonal anti-IgE antibody, has significantly improved control of these allergic diseases and introduced a new era for the management of severe allergic conditions. About 10 years of experience with omalizumab treatment for severe allergic asthma confirmed its effectiveness and safety, reducing symptoms, frequency of reliever use, and severe exacerbations in patients with intractable conditions. Omalizumab is particularly useful in childhood asthma, where atopic conditions often determine clinical courses of asthma. Recently, omalizumab is approved for the treatment of chronic spontaneous urticaria (CSU) with the fixed dose of 300 mg. Although the mechanisms underlying the actions of omalizumab in CSU are not fully clarified, nearly 90% of patients with CSU showed a complete or a partial response to omalizumab treatment. Furthermore, omalizumab is just approved for the treatment of severe Japanese cedar pollinosis (JC) based on the successful results of an add-on study of omalizumab for inadequately controlled severe pollinosis despite antihistamines and nasal corticosteroids. For proper use of omalizumab to treat severe JC, co-administration of antihistamines is necessary, while patients should meet the criteria including strong sensitization to Japanese cedar pollen (≥class 3) and poor control under standard treatment. In the management of severe allergic diseases using omalizumab, issues including cost and concerns about relapse after its discontinuation should be overcome. At the same time, possibilities for application to other intractable allergic diseases should be considered.
Topics: Animals; Anti-Allergic Agents; Antibodies, Monoclonal; Humans; Hypersensitivity; Immunoglobulin E; Omalizumab
PubMed: 32067933
DOI: 10.1016/j.alit.2020.01.004 -
The Journal of Allergy and Clinical... Jun 2023Omalizumab, an anti-IgE antibody, has clinical efficacy against respiratory symptoms of aspirin-exacerbated respiratory disease (AERD). However, some patients with AERD... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Omalizumab, an anti-IgE antibody, has clinical efficacy against respiratory symptoms of aspirin-exacerbated respiratory disease (AERD). However, some patients with AERD also present with extrarespiratory (chest, gastrointestinal, and/or cutaneous) symptoms, which are resistant to conventional treatment but can be alleviated by systemic corticosteroids.
OBJECTIVE
We evaluated the efficacy of omalizumab on extrarespiratory symptoms related to AERD.
METHODS
In study 1, a total of 27 consecutive patients with AERD initially prescribed omalizumab at Sagamihara National Hospital between July 2009 and March 2019 were retrospectively studied. Frequency of exacerbations of AERD-related extrarespiratory symptoms was compared before and after omalizumab treatment. In study 2, we reported 3 AERD cases with aspirin challenge-induced extrarespiratory symptoms among patients studied in our previous randomized trial (registration UMIN000018777), which evaluated the effects of omalizumab on hypersensitivity reactions during aspirin challenge to AERD patients. Extrarespiratory symptoms induced during the aspirin challenge were compared between placebo and omalizumab phases.
RESULTS
In study 1, omalizumab treatment was associated with decrease in frequency of exacerbation of chest pain (no. [%] of patients with exacerbation frequency ≥1 time per year, 6 [22.2%] vs 0; P < .001), gastrointestinal symptoms (9 [33.3%] vs 2 [7.4%]; P = .016), and cutaneous symptoms (16 [59.3%] vs 2 [7.4%]; P < .001), even under conditions of treatment-related reduction in systemic corticosteroid dose. Omalizumab also attenuated all the extrarespiratory symptoms during aspirin challenge in study 2.
CONCLUSION
Omalizumab ameliorated extrarespiratory symptoms at baseline (without aspirin exposure) and during aspirin challenge.
Topics: Humans; Adrenal Cortex Hormones; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Asthma, Aspirin-Induced; Omalizumab; Retrospective Studies; Sinusitis
PubMed: 36967017
DOI: 10.1016/j.jaci.2023.03.014 -
Annals of Allergy, Asthma & Immunology... Jul 2023Airway hyperresponsiveness refers to an exaggerated bronchial constrictor response to a given exogenous inhaled agent and is governed by airway smooth muscle along with... (Review)
Review
Airway hyperresponsiveness refers to an exaggerated bronchial constrictor response to a given exogenous inhaled agent and is governed by airway smooth muscle along with mucosal inflammation in asthma. In recent years, the advent of biologics and antialarmins has transformed severe asthma treatment in terms of reducing oral-corticosteroid-requiring exacerbations and improving disease control, asthma quality of life, and spirometry-measured lung function. In contrast, there have been comparatively fewer studies investigating the efficacy of biologics in airway hyperresponsiveness. In this focused review, we summarize the existing evidence base in this area regarding omalizumab, mepolizumab, benralizumab, and tezepelumab.
Topics: Humans; Anti-Asthmatic Agents; Quality of Life; Asthma; Omalizumab; Biological Therapy; Biological Products
PubMed: 36841374
DOI: 10.1016/j.anai.2023.02.016 -
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 -
Parasite Immunology Feb 2023Human fungal pathogens cause a broad plethora of infections, spanning cutaneous dermatophytoses to invasive infections in immunocompromised hosts. As eukaryotic... (Review)
Review
Human fungal pathogens cause a broad plethora of infections, spanning cutaneous dermatophytoses to invasive infections in immunocompromised hosts. As eukaryotic pathogens are capable of morphotype switching, they present unique challenges both for drug development and the immunological response. Whilst current antifungal therapies are limited to the orally available triazoles, intravenous echonocandins and polyenes, and flucytosine and terbinafine, there has been recent significant progress in the antifungal armamentorium with ibrexafungerp, a novel orally available terpanoid that inhibits 1,3-beta-D-glucan-approved by Food and Drug Administration in 2021, and fosmanogepix, an orally available pro-drug of manogepix, which targets glycosylphosphatidylinositol-anchored protein maturation entering Phase 3 studies for candidaemia. A number of further candidates are in development. There has been significant use of existing immunotherapies such as recombinant interferon-γ and G-CSF for fungal disease in immunocompromised patients, and there are emerging opportunities for monoclonal antibodies targeting TH2 inflammation. Omalizumab, an anti-IgE monoclonal antibody in asthma, is now used routinely for the treatment of allergic bronchopulmonary aspergillosis, and further agents targeting IL-4 and IL-5 are being evaluated. In addition, T-cell CAR therapy is showing early promise for fungal disease. Thus, we are likely to see rapid advances to our approach to the management of fungal disease in the near future.
Topics: United States; Humans; Antifungal Agents; Mycoses; Omalizumab; Asthma; Immunotherapy
PubMed: 36403106
DOI: 10.1111/pim.12960 -
Frontiers in Immunology 2022Urticaria is a symptom of acute skin allergies that is not clearly understood, but mast cell histamine is hypothesized to cause swelling and itching. Omalizumab, an... (Review)
Review
Urticaria is a symptom of acute skin allergies that is not clearly understood, but mast cell histamine is hypothesized to cause swelling and itching. Omalizumab, an anti-human IgE antibody that traps IgE and prevents its binding to high-affinity IgE receptors, is effective in treating urticaria. We recently experienced a case of urticaria refractory to antihistamine therapy in which the peripheral-blood basophil count responded to omalizumab therapy and its withdrawal. Furthermore, the peripheral-blood basophils showed an unexpected increase in the expression of a cell surface activation marker. This phenomenon has been reported by other analyses of basophil and mast cell dynamics during omalizumab treatment. Here, we analyze these observations and formulate a hypothesis for the role of basophils in urticaria. Specifically, that activated basophils migrate to the local skin area, lowering peripheral-blood counts, omalizumab therapy alters basophilic activity and causes their stay in the peripheral blood. We hope that our analysis will focus urticaria research on basophils and reveal new aspects of its pathogenesis.
Topics: Anti-Allergic Agents; Basophils; Humans; Immunoglobulin E; Omalizumab; Urticaria
PubMed: 35663949
DOI: 10.3389/fimmu.2022.883692 -
European Review For Medical and... Sep 2019Samter's triad is the combination of asthma, aspirin sensitization, and nasal polyposis. Few data are available on the use of omalizumab in this disease. The study aimed... (Review)
Review
OBJECTIVE
Samter's triad is the combination of asthma, aspirin sensitization, and nasal polyposis. Few data are available on the use of omalizumab in this disease. The study aimed to describe the impact of omalizumab on clinical and functional parameters and the quality of life of a series of patients with Samter's triad. Moreover, we aimed to provide a review of the literature on this topic.
PATIENTS AND METHODS
We retrospectively described four patients with Samter's triad undergoing omalizumab therapy. Clinical, functional, and immunological data of these patients were collected at baseline and follow-up.
RESULTS
Reduction of asthma exacerbations and salbutamol rescue therapy were observed in all patients after anti-IgE treatment together with an improvement in the quality of life. A significant improvement in FEV1, FVC, and FEF25-75 was observed. No major side-effects were observed. A total of 14 studies regarding omalizumab in aspirin-exacerbated respiratory diseases were included in the review, comprising 78 patients. All studies reported a good efficacy in improving asthma control; restoration of aspirin tolerance was repeatedly reported.
CONCLUSIONS
The results of our case series and review of the literature suggest that omalizumab effectively improves asthma control, lung function tests, and quality of life in patients with Samter's triad.
Topics: Adult; Aged; Anti-Asthmatic Agents; Asthma; Asthma, Aspirin-Induced; Disease-Free Survival; Drug Hypersensitivity; Female; Forced Expiratory Volume; Humans; Male; Maximal Midexpiratory Flow Rate; Middle Aged; Nasal Polyps; Omalizumab; Respiratory Hypersensitivity; Sino-Nasal Outcome Test; Therapeutics; Vital Capacity
PubMed: 31599440
DOI: 10.26355/eurrev_201909_19031 -
Drug Design, Development and Therapy 2016Despite the expansion of the understanding in asthma pathophysiology and the continual advances in disease management, a small subgroup of patients remain partially... (Review)
Review
Despite the expansion of the understanding in asthma pathophysiology and the continual advances in disease management, a small subgroup of patients remain partially controlled or refractory to standard treatments. Upon the identification of immunoglobulin E and other inflammatory mediators, investigations and developments of targeted agents have thrived. Omalizumab is a humanized monoclonal antibody that specifically targets the circulating immunoglobulin E, which in turn impedes and reduces subsequent releases of the proinflammatory mediators. In the past decade, omalizumab has been proven to be efficacious and well-tolerated in the treatment of moderate-to-severe asthma in both trials and real-life studies, most notably in reducing exacerbation rates and corticosteroid use. While growing evidence has demonstrated that omalizumab may be potentially beneficial in treating other allergic diseases, its indication remains confined to treating severe allergic asthma and chronic idiopathic urticaria. Future efforts may be focused on determining the optimal length of omalizumab treatment, seeking biomarkers that could better predict treatment response, as well as extending its indications.
Topics: Anti-Asthmatic Agents; Asthma; Humans; Omalizumab
PubMed: 27528798
DOI: 10.2147/DDDT.S112208 -
Annals of Allergy, Asthma & Immunology... Aug 2021The anti-immunoglobulin E therapy, omalizumab, improves asthma control and reduces exacerbations in patients with moderate-to-severe allergic asthma. However, it has...
BACKGROUND
The anti-immunoglobulin E therapy, omalizumab, improves asthma control and reduces exacerbations in patients with moderate-to-severe allergic asthma. However, it has been suggested that omalizumab should be reserved for highly allergic patients with multiple allergen sensitivities or perennial-only sensitivities.
OBJECTIVE
To examine impact of allergy burden, including number and type of allergen sensitivities, on omalizumab response in a real-world setting.
METHODS
This post hoc analysis evaluated a subset of omalizumab-treated patients from the Prospective Observational Study to Evaluate Predictors of Clinical Effectiveness in Response to Omalizumab (NCT01922037) who had completed 13 allergen assessments (N=478). Patients were classified by allergen burden (nonsensitized, 1, 2-4, or ≥5 allergen sensitivities) and type of allergen (nonsensitized, seasonal, perennial, or both). Outcome measures included exacerbation rate vs previous year and improvements in lung function and Asthma Quality of Life Questionnaire (AQLQ).
RESULTS
Comparable adjusted exacerbation rates were observed after omalizumab initiation, regardless of number or type of allergen sensitizations (0.56-0.85/y). Improvements in forced expiratory volume in 1 second from baseline at months 6 (0.03-0.09 L) and 12 (-0.08 to 0.08 L) were also similar across subgroups. Least squares mean change in AQLQ from baseline at months 6 (1.0-1.2) and 12 (1.1-1.4) was comparable across patient subgroups, and similar percentages of patients achieved AQLQ minimal clinically important difference of at least a 0.5-point improvement at month 6 (71%-75%), which was maintained or improved to month 12 (71%-89%). In all analyses, 95% confidence intervals overlapped.
CONCLUSION
Overall findings suggest that patients with allergic asthma achieved comparable improvements across distinct outcome measures after omalizumab therapy in a real-world setting, regardless of number and type of allergen sensitizations.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT01922037.
Topics: Adult; Anti-Asthmatic Agents; Antibodies, Anti-Idiotypic; Asthma; Female; Forced Expiratory Volume; Humans; Immunoglobulin E; Male; Middle Aged; Omalizumab; Prospective Studies; Quality of Life
PubMed: 33838339
DOI: 10.1016/j.anai.2021.04.002 -
International Archives of Allergy and... 2023Chronic urticaria (CU) is a common skin condition that can be divided into chronic spontaneous urticaria (CSU) and chronic inducible urticaria (CIndU). Omalizumab is one...
INTRODUCTION
Chronic urticaria (CU) is a common skin condition that can be divided into chronic spontaneous urticaria (CSU) and chronic inducible urticaria (CIndU). Omalizumab is one treatment option for CU, but currently there are limited clinical studies of omalizumab's efficacy for treating CU in Chinese patients. This study sought to investigate the efficacy and safety of omalizumab treatment for CU patients in a Chinese patient population. Specifically, we aimed to compare the differential efficacy of omalizumab for CSU and CIndU patients and predict risk factors for recurrence.
METHODS
We completed a retrospective clinical data review of 130 CU patients who received omalizumab treatment from August 2020 to May 2022, with a maximum follow-up period of 18 months.
RESULTS
A total of 108 CSU patients and 22 CIndU patients were included in the study. After treatment with omalizumab, the response rate in the CSU group was higher than that in the CIndU group (93.5% vs. 68.2%), and CSU patients accounted for a higher proportion of responders and early responders (responders: 87.1% vs. 12.9%, p < 0.001; early responders: 95.7% vs. 4.3%, p = 0.001). Nonresponders had lower total immunoglobulin E (IgE) levels (75.0 vs. 167.5 IU/mL, p = 0.046) and a relatively shorter duration of treatment (1.0 vs. 3.0 months, p = 0.009) compared to responders. Early responders had shorter disease duration (1.0 vs. 3.0 years, p = 0.028), higher baseline UCT (4.0 vs. 2.0, p = 0.034), lower baseline DLQI (18.0 vs. 18.5, p = 0.026), and shorter total treatment time (2.0 vs. 4.0 months, p < 0.001) compared to late responders. All adverse events reported during treatment were mild. Seventy-four patients with CU discontinued the drug after achieving complete disease control, of which 26 (35.1%) relapsed for 2.0 months (interquartile range: 1.0-3.0 months). Compared with nonrelapsed patients, relapsed patients often had other allergic diseases (42.3% vs. 18.8%, p = 0.029), higher basal levels of total IgE (263.0 vs. 140.0 IU/mL, p = 0.033), and longer disease duration (4.2 vs. 1.0 years, p = 0.002). Relapsed patients could still achieve good disease control after restarting omalizumab therapy.
CONCLUSION
Omalizumab was effective and safe for CSU and CIndU patients. Patients with CSU responded more quickly to omalizumab and showed a relatively better treatment effect. However, there was a possibility of relapse after discontinuation of omalizumab after complete control of CU, and in these cases, restarting omalizumab treatment after relapse was effective.
Topics: Humans; Omalizumab; Anti-Allergic Agents; Chronic Inducible Urticaria; Retrospective Studies; Urticaria; Chronic Urticaria; Chronic Disease; Recurrence; Immunoglobulin E; Treatment Outcome
PubMed: 36996780
DOI: 10.1159/000529250