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International Forum of Allergy &... Feb 2023Comparative effectiveness research between endoscopic sinus surgery (ESS) and biologic therapy for severe chronic rhinosinusitis with nasal polyposis (CRSwNP) is a...
BACKGROUND
Comparative effectiveness research between endoscopic sinus surgery (ESS) and biologic therapy for severe chronic rhinosinusitis with nasal polyposis (CRSwNP) is a nascent field as new therapeutic modalities become clinically available.
METHODS
A prospective, multicenter cohort of CRSwNP patients, undergoing ESS between 2011 and 2019, were compared to phase-3 biologic trial data. Patients undergoing ESS received baseline nasal endoscopy quantified via Lund-Kennedy (LK) grading. Patients meeting inclusion criteria, modified from Dupilumab-LIBERTY-NP-24&52, omalizumab-POLYP-1&2, and Mepolizumab-SYNAPSE clinical trials, were included in this study. Baseline characteristics and outcome measures were compared between these cohorts at 24 weeks and 52 weeks, when possible.
RESULTS
A total of 111 CRSwNP patients met modified inclusion criteria. There were no statistically significant differences in baseline age, sex, asthma status, aspirin-exacerbated respiratory disease status, smell identification, LK-polyp score, and Lund-Mackay computed tomography (CT) scores between ESS and biologic groups. At 24 weeks, ESS demonstrated significantly greater improvements in 22-item Sino-Nasal Outcome Test (SNOT-22) compared to one (of two) dupilumab trials (p < 0.05) and both omalizumab trials (p < 0.001). ESS associated with significantly lower nasal polyp scores (NPS) compared to dupilumab (p < 0.001) and omalizumab (p < 0.001), despite comparable improvements in smell identification (p > 0.05). At 52 weeks, ESS resulted in statistically similar improvement in SNOT-22 scores compared to dupilumab (p = 0.21), but NPS remained significantly lower in the ESS group compared to dupilumab (p < 0.001) and mepolizumab (p < 0.001).
CONCLUSION
At 24 weeks and 52 weeks, ESS offers comparable SNOT-22 improvements compared to dupilumab. ESS and dupilumab offer comparable improvement in smell identification at 24 weeks. Compared to omalizumab, ESS offers superior SNOT-22 improvements. ESS offers significantly greater reductions in polyp size compared to omalizumab, dupilumab, and mepolizumab therapies.
Topics: Humans; Nasal Polyps; Prospective Studies; Omalizumab; Rhinitis; Sinusitis; Biological Products; Endoscopy; Chronic Disease; Treatment Outcome
PubMed: 35980852
DOI: 10.1002/alr.23059 -
Advances in Therapy Nov 2023Patients with uncontrolled, allergic severe asthma may be prescribed biologic therapies to reduce exacerbations and improve disease control. Randomized controlled trials... (Review)
Review
Patients with uncontrolled, allergic severe asthma may be prescribed biologic therapies to reduce exacerbations and improve disease control. Randomized controlled trials (RCTs) of these therapies have differed in design, with varying results overall and by baseline blood eosinophil count (BEC). This study describes published annualized asthma exacerbation rate (AAER) reductions from RCTs in patients with allergic severe asthma, overall and by baseline BEC category. A literature search was performed to identify published phase 3 RCT data of US Food and Drug Administration-approved biologics for severe asthma in patients with severe, uncontrolled asthma and confirmed sensitization to perennial aeroallergens. Analyses focused on AAER reduction versus placebo in the overall population and/or in those with an elevated or low BEC at baseline or screening. Baseline serum total immunoglobulin E levels varied between RCT populations. In patients with allergic severe asthma across all BEC categories, data were available for tezepelumab, dupilumab, benralizumab and omalizumab only; the greatest AAER reduction was observed with tezepelumab. In patients with allergic severe asthma and BECs of ≥ 260 cells/µL or ≥ 300 cells/μL, AAER reductions were observed with all biologics (tezepelumab, dupilumab, mepolizumab, benralizumab and omalizumab); the greatest AAER reduction was observed with tezepelumab and the smallest AAER reduction was observed with omalizumab. In patients with allergic severe asthma and BECs of < 260 cells/µL or < 300 cells/μL (regardless of historical BEC), an AAER reduction was observed with tezepelumab but not with benralizumab or omalizumab. Differential mechanisms of action may explain the differences in results observed between biologics. Among patients with allergic severe asthma, the efficacy of biologics in RCTs varied considerably overall and by BEC. Tezepelumab was the only biologic to demonstrate AAER reductions consistently across all subgroups. These differences can inform provider treatment decisions when selecting biologic treatments for patients with allergic severe asthma.
Topics: Humans; Eosinophils; Omalizumab; Anti-Asthmatic Agents; Asthma; Biological Products
PubMed: 37698716
DOI: 10.1007/s12325-023-02647-2 -
European Review For Medical and... Oct 2023This paper aims to review biologics in allergic rhinitis (AR). Biologic agents of Omalizumab, Dupilumab, Mepolizumab, Reslizumab, and Benralizumab are reviewed in... (Review)
Review
This paper aims to review biologics in allergic rhinitis (AR). Biologic agents of Omalizumab, Dupilumab, Mepolizumab, Reslizumab, and Benralizumab are reviewed in detail. The search is performed in "Pubmed," "Google," Google Scholar" and EBSCO Academic Search Ultimate (EKUAL) database of Kırıkkale University Library from 2021 to 2000, and randomized and/or placebo-controlled studies, review papers, meta-analysis, and reports are taken into consideration. The search was performed with the keywords of "allergic rhinitis," "biologics," "biologic agents," "Omalizumab," "Dupilumab," "Mepolizumab," "Reslizumab," "Benralizumab," "Anti IgE," "Anti-IL-4/IL-13", "Anti IL-5". Search is also performed in the "U.S. Food and Drug Administration" (FDA) and "European Medicines Agency" (EMA) web systems. Biological agents such as monoclonal antibodies (MAb) in treatment are called biological therapy or biotherapy. Omalizumab is a humanized Anti-IgE monoclonal antibody. Omalizumab treatment improved the Daily Nasal Rescue Medication Score (DNSSS) and decreased the use of antiallergic drugs in seasonal and perennial AR and rhino-conjunctivitis. Omalizumab is also used in specific immunotherapy patients with allergic rhinitis and reduced allergic reactions associated with allergen immunotherapy, such as anaphylaxis. Dupilumab is an Anti-IL-4/IL-13 biologic agent. Dupilumab treatment significantly improved sino-nasal Outcome Test (SNOT-22) total scores in perennial allergic rhinitis. Anti-IL-5 monoclonal antibodies of Mepolizumab, Reslizumab Benralizumab reduce the number of eosinophils in the blood and tissue, corticosteroid addiction and asthma attacks are reduced, and their use in the treatment of severe eosinophilic asthma has been approved. Biologics, especially Omalizumab, and Dupilumab, may be used more in allergic rhinitis.
Topics: Humans; Anti-Asthmatic Agents; Antibodies, Monoclonal; Asthma; Biological Products; Interleukin-13; Omalizumab; Rhinitis, Allergic
PubMed: 37869947
DOI: 10.26355/eurrev_202310_34069 -
The Journal of Allergy and Clinical... Jul 2021Assessment of clinical outcomes in the real-world corroborates findings from randomized controlled trials (RCTs). (Meta-Analysis)
Meta-Analysis
BACKGROUND
Assessment of clinical outcomes in the real-world corroborates findings from randomized controlled trials (RCTs).
OBJECTIVE
This meta-analysis evaluated real-world data of omalizumab on treatment response, lung function, exacerbations, oral corticosteroid (OCS) use, patient-reported outcomes (PROs), health care resource utilization (HCRU), and school/work absenteeism at 4, 6, and 12 months after treatment.
METHODS
Observational studies in patients with severe allergic asthma (≥6 years) treated with omalizumab for ≥16 weeks, published from January 2005 to October 2018, were retrieved from PubMed, Embase, and Cochrane. A random-effects model was used to assess heterogeneity.
RESULTS
In total, 86 publications were included. Global evaluation of treatment effectiveness (GETE) was good/excellent in 77% patients at 16 weeks (risk difference: 0.77; 95% confidence interval [CI]: 0.70-0.84; I = 96%) and in 82% patients at 12 months (0.82, 0.73-0.91; 97%). The mean improvement in forced expiratory volume in 1 second was 160, 220, and 250 mL at 16 weeks, 6 months, and 12 months, respectively. There was a decrease in Asthma Control Questionnaire score at 16 weeks (-1.14), 6 months (-1.56), and 12 months (-1.13) after omalizumab therapy. Omalizumab significantly reduced annualized rate of severe exacerbations (risk ratio [RR]: 0.41, 95% CI: 0.30-0.56; I = 96%), proportion of patients receiving OCS (RR: 0.59, 95% CI: 0.47-0.75; I = 96%), and number of unscheduled physician visits (mean difference: -2.34, 95% CI: -3.54 to -1.13; I = 98%) at 12 months versus baseline.
CONCLUSION
The consistent improvements in GETE, lung function, and PROs, and reductions in asthma exacerbations, OCS use, and HCRU with add-on omalizumab in real-life confirm and complement the efficacy data of RCTs.
Topics: Anti-Asthmatic Agents; Asthma; Humans; Hypersensitivity; Omalizumab; Quality of Life; Treatment Outcome
PubMed: 33486142
DOI: 10.1016/j.jaip.2021.01.011 -
Allergy Feb 2024Asthma remission has emerged as a potential treatment goal. This study evaluated the effectiveness of two biologics (mepolizumab/omalizumab) in achieving asthma... (Observational Study)
Observational Study
BACKGROUND
Asthma remission has emerged as a potential treatment goal. This study evaluated the effectiveness of two biologics (mepolizumab/omalizumab) in achieving asthma remission.
METHODS
This observational study included 453 severe asthma patients (41% male; mean age ± SD 55.7 ± 14.7 years) from two real-world drug registries: the Australian Mepolizumab Registry and the Australian Xolair Registry. The composite outcome clinical remission was defined as zero exacerbations and zero oral corticosteroids during the previous 6 months assessed at 12 months and 5-item Asthma Control Questionnaire (ACQ-5) ≤1 at 12 months. We also assessed clinical remission plus optimization (post-bronchodilator FEV1 ≥80%) or stabilization (post-bronchodilator FEV1 not greater than 5% decline from baseline) of lung function at 12 months. Sensitivity analyses explored various cut-offs of ACQ-5/FEV1 scores. The predictors of clinical remission were identified.
RESULTS
29.3% (73/249) of AMR and 22.8% (37/162) of AXR cohort met the criteria for clinical remission. When lung function criteria were added, the remission rates were reduced to 25.2% and 19.1%, respectively. Sensitivity analyses identified that the remission rate ranged between 18.1% and 34.9% in the AMR cohort and 10.6% and 27.2% in the AXR cohort. Better lung function, lower body mass index, mild disease and absence of comorbidities such as obesity, depression and osteoporosis predicted the odds of achieving clinical remission.
CONCLUSION
Biologic treatment with mepolizumab or omalizumab for severe asthma-induced asthma remission in a subgroup of patients. Remission on treatment may be an achievable treatment target and future studies should consider remission as an outcome measure.
Topics: Humans; Male; Female; Omalizumab; Anti-Asthmatic Agents; Bronchodilator Agents; Australia; Asthma; Biological Products; Antibodies, Monoclonal, Humanized
PubMed: 37632144
DOI: 10.1111/all.15867 -
The Journal of Allergy and Clinical... Feb 2023Patients with food allergy may be advised to introduce specific foods into their diets, both to increase tolerance gradually and as next steps after completing oral... (Clinical Trial)
Clinical Trial
Retail Food Equivalents for Post-Oral Immunotherapy Dosing in the Omalizumab as Monotherapy and as Adjunct Therapy to Multi-Allergen Oral Immunotherapy in Food-Allergic Children and Adults (OUtMATCH) Clinical Trial.
BACKGROUND
Patients with food allergy may be advised to introduce specific foods into their diets, both to increase tolerance gradually and as next steps after completing oral immunotherapy or other therapeutic interventions. However, the safe use of retail foods depends on the ability to establish the specific allergen protein content of these foods.
OBJECTIVE
To develop a systematic approach to estimate the protein content of peanut, milk, egg, wheat, cashew, hazelnut, and walnut in a variety of retail food equivalents for each allergen and associated patient education materials.
METHOD
We created an algorithm that used a multistep process with information from product food labels, nutrient databases, independent weighing and measuring of foods, and information provided by manufacturers, including certificates of analysis, and e-mail communication to estimate the allergen protein content of multiple retail foods for each of seven allergens. Once a variety of retail food equivalents for each allergen and allergen serving size was determined, we developed participant education handouts, which were reviewed by study teams at 10 food allergy centers, the National Institute of Allergy and Infectious Diseases, and the Consortium for Food Allergy Research coordinating center. After 1 year of use, multiple queries were addressed and the retail food equivalents and educational materials were reviewed and edited.
RESULTS
We identified a variety of retail food equivalents for seven allergens at six serving sizes, and created 48 unique patient education materials.
CONCLUSION
Our results provide extensive guidance on a variety of retail equivalents for seven foods, and a method to estimate retail food protein equivalents systematically with ongoing reassessment.
Topics: Adult; Child; Humans; Allergens; Desensitization, Immunologic; Food Hypersensitivity; Nuts; Omalizumab
PubMed: 37113037
DOI: 10.1016/j.jaip.2022.10.022 -
Clinical and Experimental Allergy :... Apr 2023Allergic asthma is the most common phenotype among patients with severe asthma. In the phase 3 NAVIGATOR study (NCT03347279), tezepelumab significantly reduced the... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Allergic asthma is the most common phenotype among patients with severe asthma. In the phase 3 NAVIGATOR study (NCT03347279), tezepelumab significantly reduced the annualized asthma exacerbation rate (AAER) versus placebo in patients with severe, uncontrolled asthma. This exploratory analysis evaluated the efficacy of tezepelumab in NAVIGATOR participants with evidence of severe allergic asthma.
METHODS
Patients (12-80 years old) receiving medium- or high-dose inhaled corticosteroids and ≥ 1 additional controller medication, with or without oral corticosteroids, were randomized to tezepelumab 210 mg or placebo subcutaneously every 4 weeks for 52 weeks in NAVIGATOR. In this analysis, the AAER, forced expiratory volume in 1 second (FEV ), patient-reported outcomes (PROs), and type 2 biomarker levels were evaluated in patients grouped by sensitivity to perennial aeroallergens, confirmed symptomatic allergy, and eligibility for omalizumab treatment according to the United States (OMA-US) and the European Union (OMA-EU) prescribing information, including subgroups according to baseline blood eosinophil counts and fractional exhaled nitric oxide (FeNO) levels.
RESULTS
Of 1059 patients who received treatment in NAVIGATOR, 680 (64%) had perennial aeroallergen sensitivity and 318 (30%) had confirmed symptomatic allergy; 379 (36%) and 359 (34%) patients were OMA-US- and OMA-EU-eligible, respectively. Tezepelumab reduced the AAER over 52 weeks versus placebo by 58% (95% confidence interval [CI]: 47-67) to 68% (95% CI: 55-77) across these subgroups. Among omalizumab-eligible patients, AAERs were reduced in patients across baseline blood eosinophil counts and FeNO levels. Tezepelumab improved FEV and PROs, and reduced type 2 biomarkers, versus placebo in patients with and without perennial allergy.
CONCLUSIONS
Tezepelumab was efficacious in patients with severe, uncontrolled asthma with evidence of allergic inflammation, defined by multiple clinically relevant definitions. These findings further support the benefits of tezepelumab in a broad population of patients with severe asthma, including those with severe allergic asthma.
Topics: Humans; Omalizumab; Anti-Asthmatic Agents; Asthma; Adrenal Cortex Hormones; Double-Blind Method
PubMed: 36507576
DOI: 10.1111/cea.14256 -
Current Opinion in Allergy and Clinical... Oct 2023The purpose of this literature review was to review the latest use of biologics in the management of anaphylaxis. The methodology was to highlight both the nonbiologic... (Review)
Review
PURPOSE OF REVIEW
The purpose of this literature review was to review the latest use of biologics in the management of anaphylaxis. The methodology was to highlight both the nonbiologic management of anaphylaxis and the biologic management and how they can be used in conjunction with each other.
RECENT FINDINGS
As the phenotypes and endotypes of anaphylaxis are better portrayed, it furthers our understanding of the mechanisms of anaphylaxis. New applications of existing biologics to the prevention of anaphylaxis are described.
SUMMARY
Anaphylaxis is a potentially life-threatening acute hypersensitivity reaction affecting up to 16.8% of the U.S. population. Acute management entails swift identification, removal of the causative agent, and the prevention of cardiovascular collapse, firstly with epinephrine. Adjunctive treatments such as antihistamines work to prevent anaphylaxis from recurring. Biologic management of anaphylaxis involves the use of large-molecule drugs such as monoclonal antibodies. Omalizumab, an IgG1 monoclonal antibody targeting unbound IgE, is the most prevalent and widely studied biologic in the prevention of anaphylaxis. Other monoclonal antibodies in development or approved for other indications, such as ligelizumab, quilizumab, MEDI4212, and dupilumab, may also have potential for preventing anaphylaxis through various mechanisms.
Topics: Humans; Anaphylaxis; Omalizumab; Antibodies, Monoclonal; Epinephrine; Immunoglobulin E; Biological Products
PubMed: 37527059
DOI: 10.1097/ACI.0000000000000940 -
Annals of Allergy, Asthma & Immunology... Jul 2023To review the safety and efficacy of anti-immunoglobulin E (IgE) monotherapy or as an adjunct to oral immunotherapy (OIT) in the treatment of IgE-mediated food allergy. (Review)
Review
OBJECTIVE
To review the safety and efficacy of anti-immunoglobulin E (IgE) monotherapy or as an adjunct to oral immunotherapy (OIT) in the treatment of IgE-mediated food allergy.
DATA SOURCES
Literature searches were performed using the Excerpta Medica dataBASE, Medline, Scopus, and PubMed Central to identify articles in English related to food allergy and anti-IgE therapies, including omalizumab and ligelizemab.
STUDY SELECTIONS
Original research articles reviewed include interventional studies, retrospective and prospective observational studies, peer-reviewed reviews, and systematic reviews. Data were reviewed and summarized.
RESULTS
Here, we discuss the current anti-IgE therapies being studied as a potential treatment option for food allergy. We also review trial design, safety, and efficacy data on the use of anti-IgE therapies as monotherapy or in combination with OIT for food allergies. Finally, we discuss clinical trials in progress using omalizumab and ligelizumab and highlight important clinical considerations.
CONCLUSION
Over the past 20 years, substantial progress has been made in understanding the potential role of anti-IgE therapies for food allergy. Anti-IgE therapies seem to be a promising option that may increase reaction dose thresholds and decrease time to reach OIT maintenance and OIT dosing-related reactions. Two phase 3 trials are currently in progress studying anti-IgE potential monotherapy for the treatment of peanut and multifood allergies. It is important for clinicians to be aware of these emerging treatment options.
Topics: Humans; Omalizumab; Immunoglobulin E; Desensitization, Immunologic; Retrospective Studies; Administration, Oral; Food Hypersensitivity; Allergens; Observational Studies as Topic
PubMed: 37031775
DOI: 10.1016/j.anai.2023.03.030 -
Allergy Jan 2022Chronic spontaneous urticaria (CSU) imposes a significant burden on patients, families and healthcare systems. Management is difficult, due to disease heterogeneity and...
Chronic spontaneous urticaria (CSU) imposes a significant burden on patients, families and healthcare systems. Management is difficult, due to disease heterogeneity and insufficient efficacy of classical drugs such as H R-antihistamines. Better understanding of the mechanisms has enabled a stratified approach to the management of CSU, supporting the use of targeted treatment with omalizumab. However, many practical issues including selection of responders, the definition of response, strategies to enhance the responder rate, the duration of treatment and its regimen (in the clinic or home-based) and its cost-effectiveness still require further clarification. The EAACI Guidelines on the use of omalizumab in CSU follow the GRADE approach in formulating recommendations for each outcome. In addition, future therapeutic approaches and perspectives as well as research priorities are discussed.
Topics: Adolescent; Adult; Anti-Allergic Agents; Biological Products; Child; Chronic Disease; Chronic Urticaria; Humans; Omalizumab; Treatment Outcome; Urticaria
PubMed: 34324716
DOI: 10.1111/all.15030