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The New England Journal of Medicine Mar 2024Food allergies are common and are associated with substantial morbidity; the only approved treatment is oral immunotherapy for peanut allergy. (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Food allergies are common and are associated with substantial morbidity; the only approved treatment is oral immunotherapy for peanut allergy.
METHODS
In this trial, we assessed whether omalizumab, a monoclonal anti-IgE antibody, would be effective and safe as monotherapy in patients with multiple food allergies. Persons 1 to 55 years of age who were allergic to peanuts and at least two other trial-specified foods (cashew, milk, egg, walnut, wheat, and hazelnut) were screened. Inclusion required a reaction to a food challenge of 100 mg or less of peanut protein and 300 mg or less of the two other foods. Participants were randomly assigned, in a 2:1 ratio, to receive omalizumab or placebo administered subcutaneously (with the dose based on weight and IgE levels) every 2 to 4 weeks for 16 to 20 weeks, after which the challenges were repeated. The primary end point was ingestion of peanut protein in a single dose of 600 mg or more without dose-limiting symptoms. The three key secondary end points were the consumption of cashew, of milk, and of egg in single doses of at least 1000 mg each without dose-limiting symptoms. The first 60 participants (59 of whom were children or adolescents) who completed this first stage were enrolled in a 24-week open-label extension.
RESULTS
Of the 462 persons who were screened, 180 underwent randomization. The analysis population consisted of the 177 children and adolescents (1 to 17 years of age). A total of 79 of the 118 participants (67%) receiving omalizumab met the primary end-point criteria, as compared with 4 of the 59 participants (7%) receiving placebo (P<0.001). Results for the key secondary end points were consistent with those of the primary end point (cashew, 41% vs. 3%; milk, 66% vs. 10%; egg, 67% vs. 0%; P<0.001 for all comparisons). Safety end points did not differ between the groups, aside from more injection-site reactions in the omalizumab group.
CONCLUSIONS
In persons as young as 1 year of age with multiple food allergies, omalizumab treatment for 16 weeks was superior to placebo in increasing the reaction threshold for peanut and other common food allergens. (Funded by the National Institute of Allergy and Infectious Diseases and others; ClinicalTrials.gov number, NCT03881696.).
Topics: Adolescent; Child; Humans; Infant; Allergens; Arachis; Desensitization, Immunologic; Food Hypersensitivity; Omalizumab; Peanut Hypersensitivity; Anti-Allergic Agents; Child, Preschool; Young Adult; Adult; Middle Aged
PubMed: 38407394
DOI: 10.1056/NEJMoa2312382 -
Medicina Clinica Nov 2023Urticaria is a skin-condition characterized by sudden-onset pruritic wheals with/without angioedema. Urticaria can be acute or chronic. Chronic urticaria may be... (Review)
Review
Urticaria is a skin-condition characterized by sudden-onset pruritic wheals with/without angioedema. Urticaria can be acute or chronic. Chronic urticaria may be spontaneous or inducible, based on absence/presence of specific triggers. Chronic spontaneous urticaria is most frequent (∼80%). Urticaria is primarily a mast-cell mediated histaminergic-disorder. Recently, other inflammatory cells and pro-inflammatory cytokines have been implicated. Deeper understanding has unmasked two endotypes - IgE-mediated type I autoimmunity/autoallergy and IgG-mediated type IIb autoimmunity. Current treatment recommendation involving second-generation H1-antihistamines, omalizumab and cyclosporine is effective in 60-80% patients. So, newer treatment options are being explored based on emerging targets. Despite being non-lethal, urticaria considerably impairs patient's quality-of-life and may be associated with extra-cutaneous comorbidities. Several "patient reported outcome measures" have been proposed to evaluate disease-activity, impact and control, for effective treatment modulation till complete disease control. This review discusses the current understanding about urticaria and its future directions, to facilitate optimum evidenced-based care.
Topics: Humans; Chronic Disease; Urticaria; Angioedema; Omalizumab; Skin
PubMed: 37537021
DOI: 10.1016/j.medcli.2023.06.026 -
The Journal of Allergy and Clinical... Jan 2023Management of asthma in adults has advanced in the past 10 years. Central to these advances has been further clarification of type (T) 2 mechanisms of airway...
Management of asthma in adults has advanced in the past 10 years. Central to these advances has been further clarification of type (T) 2 mechanisms of airway inflammation and utilization of T2 biomarkers, that is, eosinophils and fractional exhaled nitric oxide. In addition, epithelial cells are emerging as significant contributors to inflammation through generation of alarmins to initiate local injury as well as downstream pathways. Five new biologics, mepolizumab, benralizumab, reslizumab, dupilumab, and tezepelumab, were approved to join omalizumab and revolutionize severe asthma treatment. These biologics significantly prevent exacerbations to spare systemic corticosteroids use and their side effects. Guidelines attest to the effectiveness of inhaled corticosteroids/long-acting β-agonists (formoterol) for both maintenance and rescue therapy. Focused updates to the Expert Panel Report addressed limited but specific questions relevant to asthma control. Future guidelines should include phenotype/endotype-directed therapeutics to gain more precision-directed treatment.
Topics: Humans; Anti-Asthmatic Agents; Asthma; Omalizumab; Biological Products; Adrenal Cortex Hormones
PubMed: 36283607
DOI: 10.1016/j.jaip.2022.10.015 -
The Journal of Allergy and Clinical... Sep 2020Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by IgE hyperproduction and eosinophilic inflammation. The anti-IgE antibody, omalizumab, has... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by IgE hyperproduction and eosinophilic inflammation. The anti-IgE antibody, omalizumab, has demonstrated efficacy in patients with CRSwNP and comorbid asthma previously.
OBJECTIVE
Our aim was to determine omalizumab safety and efficacy in CRSwNP in phase 3 trials (POLYP 1 and POLYP 2).
METHODS
Adults with CRSwNP with inadequate response to intranasal corticosteroids were randomized (1:1) to omalizumab or placebo and intranasal mometasone for 24 weeks. Coprimary end points included change from baseline to week 24 in Nasal Polyp Score (NPS) and Nasal Congestion Score. Secondary end points included change from baseline to week 24 in Sino-Nasal Outcome Test-22 (SNOT-22) score, University of Pennsylvania Smell Identification Test, sense of smell, postnasal drip, runny nose, and adverse events.
RESULTS
Patients in POLYP 1 (n = 138) and POLYP 2 (n = 127) exhibited severe CRSwNP and substantial quality of life impairment evidenced by a mean NPS higher than 6 and SNOT-22 score of approximately 60. Both studies met both the coprimary end points. SNOT-22 score, University of Pennsylvania Smell Identification Test score, sense of smell, postnasal drip, and runny nose were also significantly improved for omalizumab versus placebo. In POLYP 1 and POLYP 2, the mean changes from baseline at week 24 for omalizumab versus placebo were as follows: NPS, -1.08 versus 0.06 (P < .0001) and -0.90 versus -0.31 (P = .0140); Nasal Congestion Score, -0.89 versus -0.35 (P = .0004) and -0.70 versus -0.20 (P = .0017); and SNOT-22 score, -24.7 versus -8.6 (P < .0001) and -21.6 versus -6.6 (P < .0001). Adverse events were similar between groups.
CONCLUSION
Omalizumab significantly improved endoscopic, clinical, and patient-reported outcomes in severe CRSwNP with inadequate response to intranasal corticosteroids, and it was well tolerated.
Topics: Adrenal Cortex Hormones; Adult; Anti-Allergic Agents; Chronic Disease; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Mometasone Furoate; Nasal Polyps; Omalizumab; Rhinitis; Sinusitis; Treatment Outcome
PubMed: 32524991
DOI: 10.1016/j.jaci.2020.05.032 -
The Journal of Allergy and Clinical... May 2023Multiple mAbs are currently approved for the treatment of asthma. However, there is limited evidence on their comparative effectiveness. (Clinical Trial)
Clinical Trial
BACKGROUND
Multiple mAbs are currently approved for the treatment of asthma. However, there is limited evidence on their comparative effectiveness.
OBJECTIVE
Our aim was to compare the effectiveness of omalizumab, mepolizumab, and dupilumab in individuals with moderate-to-severe asthma.
METHODS
We emulated a hypothetical randomized trial using electronic health records from a large US-based academic health care system. Participants aged 18 years or older with baseline IgE levels between 30 and 700 IU/mL and peripheral eosinophil counts of at least 150 cells/μL were eligible for study inclusion. The study period extended from March 2016 to August 2021. Outcomes included the incidence of asthma-related exacerbations and change in baseline FEV value over 12 months of follow-up.
RESULTS
In all, 68 individuals receiving dupilumab, 68 receiving omalizumab, and 65 receiving mepolizumab met the inclusion criteria. Over 12 months of follow-up, 31 exacerbations occurred over 68 person years (0.46 exacerbations per person year) in the dupilumab group, 63 over 68 person years (0.93 per person year) in the omalizumab group, and 86 over 65 person years (1.32 per person year) in the mepolizumab group (adjusted incidence rate ratios: dupilumab vs mepolizumab, 0.28 [95% CI = 0.09-0.84]; dupilumab vs omalizumab, 0.36 [95% CI = 0.12-1.09]; and omalizumab vs mepolizumab, 0.78 [95% CI = 0.32-1.91]). The differences in the change in FEV comparing patients who received the different biologics were as follows: 0.11 L (95% CI = -0.003 to 0.222 L) for dupilumab versus mepolizumab, 0.082 L (95% CI -0.040 to 0.204 L) for dupilumab versus omalizumab, and 0.026 L (95% CI -0.083 to 0.140 L) for omalizumab versus mepolizumab.
CONCLUSIONS
Among patients with asthma and eosinophil counts of at least 150 cells/μL and IgE levels of 30 to 700 kU/L, dupilumab was associated with greater improvements in exacerbation and FEV value than omalizumab and mepolizumab.
Topics: Humans; Anti-Asthmatic Agents; Asthma; Immunoglobulin E; Omalizumab; Comparative Effectiveness Research
PubMed: 36740144
DOI: 10.1016/j.jaci.2023.01.020 -
Allergology International : Official... Jan 2023Biologics have been a key component of severe asthma treatment, and there are currently biologics available that target IgE, IL-5, IL-4/IL-13, and TSLP. Randomized... (Review)
Review
Biologics have been a key component of severe asthma treatment, and there are currently biologics available that target IgE, IL-5, IL-4/IL-13, and TSLP. Randomized controlled trials have established clinical evidence, but a significant portion of patients with severe asthma in real-life settings would have been excluded from those trials. Therefore, real-world research is necessary, and there is a growing body of information about the long-term efficacy and safety of biologics. Multiple clinical phenotypes of severe asthma exist, and it is crucial to choose patients based on their phenotypes. Blood eosinophil count is an important biomarker for anti-IL-5 therapies, and FeNO and eosinophil counts serve as prediction markers for dupilumab. Reliable markers for predicting response, however, have not yet been fully established for omalizumab. Identification of clinical or biological prediction factors is crucial for the path toward clinical remission because the current treatment goal includes clinical remission, which is defined as a realistic goal for remission off treatment. Additionally, since there are now multiple biologic options and overlaps in eligibility for biologics in clinical practice, the evidence regarding the effectiveness of switching the biologics is crucial. Investigations into the clinical trajectory following the cessation of biologics are another important issue. Recent research on omalizumab, mepolizumab, benralizumab and dupilumab's real-world effectiveness, the prediction factor for the efficacy, and the impact of switching or discontinuation will be reviewed and discussed in this review.
Topics: Humans; Omalizumab; Asthma; Eosinophils; Interleukin-5; Interleukin-13; Biological Products; Anti-Asthmatic Agents
PubMed: 36543689
DOI: 10.1016/j.alit.2022.11.008 -
The Journal of Allergy and Clinical... Mar 2023Severe asthma in childhood confers substantial patient- and society-level burdens. Although biologics have been available for the management in adults and adolescents... (Review)
Review
Severe asthma in childhood confers substantial patient- and society-level burdens. Although biologics have been available for the management in adults and adolescents for nearly 20 years, research on the efficacy and safety of biologics in children and adolescents has lagged. Fortunately, more recent research specifically in children has provided an evidence base for biologic use in this age group. Most children with severe asthma demonstrate a type 2 inflammatory phenotype, the primary target of currently approved biologics. Three biologics, omalizumab, mepolizumab, and duplilumab, are Food and Drug Administration-approved for children as young as 6 years, whereas benralizumab and tezepelumab are approved for adolescents older than 12 years. All these agents reduce the rates of severe asthma exacerbations, whereas their effects on pulmonary function vary across agents. Safety profiles are reassuring, although additional long-term safety data in children are still needed. The choice of a biologic agent follows a careful assessment of other factors that contribute to uncontrolled asthma and includes biomarkers of blood eosinophils, fractional exhaled nitric oxide, allergic sensitization, and IgE levels. This review focuses on the underlying pathophysiology of childhood asthma, an approach to phenotyping patients, and the efficacy, safety, and use of biologics in children and adolescents with severe asthma.
Topics: Humans; Anti-Asthmatic Agents; Asthma; Omalizumab; Biological Factors; Biological Products
PubMed: 36702649
DOI: 10.1016/j.jaci.2023.01.002 -
Allergy Oct 2021The current therapeutic algorithm for chronic spontaneous urticaria (CSU), endorsed by the international guideline, entails treatment escalation from second-generation H... (Review)
Review
The current therapeutic algorithm for chronic spontaneous urticaria (CSU), endorsed by the international guideline, entails treatment escalation from second-generation H -antihistamines (sgAHs) to omalizumab and cyclosporine until complete response is achieved. Recently, several predictors of response to these treatment options have been described. Here, we discuss the most promising predictors of response and nonresponse to these treatments in CSU. A systematic search was performed by two independent researchers using the MEDLINE/PubMed database with specific keywords and 73 studies included in the review. Levels of evidence were categorized as strong (robust predictors), weak (emerging predictors) or no association, based on the outcome and number of studies available. High disease activity, high levels of C-reactive protein and D-dimer are robust predictors for a poor or no response to sgAHs. Poor or no response to omalizumab is robustly predicted by low serum levels of total IgE. A good response to cyclosporine is robustly predicted by a positive basophil histamine release assay, whereas low total IgE is an emerging predictor. The response to treatment with sgAHs, omalizumab and cyclosporine can be predicted by the use of markers that are readily available in routine clinical practice. Further studies are needed to confirm these predictors.
Topics: Anti-Allergic Agents; Chronic Disease; Chronic Urticaria; Histamine Antagonists; Humans; Omalizumab; Treatment Outcome; Urticaria
PubMed: 33539587
DOI: 10.1111/all.14757 -
Frontiers in Immunology 2022Bullous pemphigoid (BP) is the most common autoimmune subepidermal bullous disease of the skin. First-line treatment of systemic corticosteroids may cause serious...
BACKGROUND
Bullous pemphigoid (BP) is the most common autoimmune subepidermal bullous disease of the skin. First-line treatment of systemic corticosteroids may cause serious adverse events. Rituximab, omalizumab, and dupilumab should be explored as alternative treatment options to improve outcomes.
OBJECTIVE
To systematically review the rituximab, omalizumab, and dupilumab treatment outcomes in bullous pemphigoid.
METHODS
A PubMed, Embase, Web of Science, and Cochrane library search were conducted on March 10, 2022. A total of 75 studies were included using Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines.
RESULTS
Use of rituximab (n=122), omalizumab (n=53) and dupilumab (n=36) were reported in 211 patients with BP. Rituximab led to complete remission in 70.5% (n=86/122) and partial remission in 23.8% (n=29/122) of patients within 5.7 months, with a recurrence rate of 20.5% (n=25/122). 9.0% (n=11/122) of patients died and infection (6.6%, n=8/122) was the most common adverse event. Omalizumab led to complete remission in 67.9% (n=36/53) and partial remission in 20.8% (n=11/53) of patients within 6.6 months, with a recurrence rate of 5.7% (n=3/53). 1.9% (n=1/53) of patients died and thrombocytopenia (1.9%, n=1/53) was observed as the most common adverse event. Dupilumab led to complete remission in 66.7% (n=24/36) and partial remission in 19.4% (n=7/36) of patients within 4.5 months of treatment without any reported adverse events, with a recurrence rate of 5.6% (n=2/36).
CONCLUSIONS
Rituximab, omalizumab, and dupilumab have similar clinical benefits for BP patients. However, rituximab resulted in higher recurrence rates, adverse events, and mortality rates.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022316454.
Topics: Antibodies, Monoclonal, Humanized; Humans; Omalizumab; Pemphigoid, Bullous; Rituximab; Treatment Outcome
PubMed: 35769474
DOI: 10.3389/fimmu.2022.928621 -
International Journal of Molecular... May 2023Currently, three classes of monoclonal antibodies targeting type 2 inflammation pathways are available in Italy for the treatment of severe asthma: anti-IgE... (Review)
Review
Currently, three classes of monoclonal antibodies targeting type 2 inflammation pathways are available in Italy for the treatment of severe asthma: anti-IgE (Omalizumab), anti-IL-5/anti-IL-5Rα (Mepolizumab and Benralizumab), and anti-IL-4Rα (Dupilumab). Numerous randomized controlled trials (RCTs) and real-life studies have been conducted to define their efficacy and identify baseline patients' characteristics potentially predictive of favorable outcomes. Switching to another monoclonal antibody is recommended in case of a lack of benefits. The aim of this work is to review the current knowledge on the impact of switching biological therapies in severe asthma as well as on predictors of treatment response or failure. Almost all of the information about switching from a previous monoclonal antibody to another comes from a real-life setting. In the available studies, the most frequent initial biologic was Omalizumab and patients who were switched because of suboptimal control with a previous biologic therapy were more likely to have a higher baseline blood eosinophil count and exacerbation rate despite OCS dependence. The choice of the most suitable treatment may be guided by the patient's clinical history, biomarkers of endotype (mainly blood eosinophils and FeNO), and comorbidities (especially nasal polyposis). Due to overlapping eligibility, larger investigations characterizing the clinical profile of patients benefiting from switching to different monoclonal antibodies are needed.
Topics: Humans; Omalizumab; Asthma; Antibodies, Monoclonal; Biological Therapy; Eosinophils; Anti-Asthmatic Agents
PubMed: 37298514
DOI: 10.3390/ijms24119563