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Current Opinion in Allergy and Clinical... Apr 2019Children with poor asthma control despite maximal maintenance therapy have problematic severe asthma (PSA). A step-wise approach including objective adherence monitoring... (Review)
Review
PURPOSE OF REVIEW
Children with poor asthma control despite maximal maintenance therapy have problematic severe asthma (PSA). A step-wise approach including objective adherence monitoring and a detailed multidisciplinary team assessment to identify modifiable factors contributing to poor control is needed prior to considering therapy escalation. Pathophysiological phenotyping in those with true severe therapy-resistant asthma (STRA) and the current array of add-on therapies will be discussed.
RECENT FINDINGS
Adherence monitoring using electronic devices has shown that only 20-30% of children with PSA have STRA and need additional therapies. Omalizumab and mepolizumab are licensed for children with STRA aged 6 years and older. Although robust safety and efficacy data, with reduced exacerbations, are available for omalizumab, biomarkers predicting response to treatment are lacking. Paediatric safety data are available for mepolizumab, but efficacy data are unknown for those aged 6-11 years and minimal for those 12 years and older. A sub-group of children with STRA have neutrophilia, but the clinical significance and contribution to disease severity remains uncertain.
SUMMARY
Most children with PSA have steroid sensitive disease which improves with adherence to maintenance inhaled corticosteroids. Add-on therapies are only needed for the minority with STRA. Paediatric efficacy data of novel biologics and biomarkers that identify the optimal add-on for each child are lacking. If we are to progress toward individualized therapy for STRA, pragmatic clinical trials of biologics in accurately phenotyped children are needed.
Topics: Adrenal Cortex Hormones; Anti-Asthmatic Agents; Asthma; Child; Disease Progression; Humans; Medication Adherence; Omalizumab; Phenotype; Precision Medicine; Severity of Illness Index
PubMed: 30720474
DOI: 10.1097/ACI.0000000000000521 -
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 -
BMC Pulmonary Medicine Oct 2023Omalizumab is a valuable alternative treatment for allergic bronchopulmonary aspergillosis (ABPA). The effectiveness and safety of this medication have not been...
BACKGROUND
Omalizumab is a valuable alternative treatment for allergic bronchopulmonary aspergillosis (ABPA). The effectiveness and safety of this medication have not been confirmed. The main purpose of this study was to evaluate the effectiveness and safety of omalizumab for ABPA.
METHODS
This study involved a retrospective chart review. The main indicators used were asthma control test (ACT) scores, lung function parameters, doses of corticosteroids, acute exacerbation, hospitalization rates, total serum immunoglobulin E (IgE) levels, and blood eosinophil counts. Related adverse events were also reviewed to evaluate the safety of omalizumab.
RESULTS
Fourteen patients with ABPA were included, of whom 10 (71%) concurrently had allergic rhinitis (AR). There were improvements in the mean percentages of the forced vital capacity, percentages of the forced expiratory volume in 1 s, and ACT score after omalizumab administration (p < 0.05, p < 0.01, and p < 0.01, respectively). After the initiation of omalizumab administration, the median corticosteroid dose, acute exacerbation rate, hospitalization rate, and mean blood eosinophil count decreased when compared with the baseline values (p < 0.05, p < 0.05, p < 0.01, and p < 0.05, respectively). A reduction in the total serum IgE level was observed in patients with ABPA without AR compared with that in patients with AR (p < 0.05). One patient reported a concurrent skin rash, which spontaneously resolved without medication.
CONCLUSION
It is safe and effective to prescribe omalizumab to patients with ABPA, irrespective of whether they have AR. Dose adjustment of omalizumab is safe after disease control. The total serum IgE level might be a predictor of the effectiveness of omalizumab in patients without AR.
Topics: Humans; Omalizumab; Anti-Allergic Agents; Aspergillosis, Allergic Bronchopulmonary; Retrospective Studies; Adrenal Cortex Hormones; Rhinitis, Allergic; Immunoglobulin E
PubMed: 37833657
DOI: 10.1186/s12890-023-02696-x -
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