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Tuberkuloz Ve Toraks Jun 2023(Review)
Review
ABSTRACT
BIOLOGICS FOR THE TREATMENT OF SEVERE ASTHMA: CURRENT STATUS REPORT 2023
Severe asthma is associated with increased use of healthcare services, significant deterioration in the quality of life, and high disease and economic burden on patients and societies. Additional treatments are required for severe forms of asthma. Biological agents are recommended for the treatment of severe asthma. In this current status report, we aimed to evaluate the efficacy, effectiveness, and safety data of approved biologics; omalizumab, mepolizumab, reslizumab, benralizumab, dupilumab, and tezepelumab, in the treatment of severe asthma and appropriate patient profiles for these biologics. Pubmed and Cochrane databases based on randomized controlled trials, posthoc analyses, meta-analyses, and real-life studies examining the efficacy and effectiveness of biologics in severe asthma were searched, and the results of these studies on important asthma outcomes were reviewed. Existing studies have shown that all the approved biologic agents targeting cells, receptors, and mediators involved in type 2 inflammation in the bronchial wall in severe asthma significantly reduce asthma exacerbations, reduce the need for oral corticosteroids, and improve asthma control, quality of life, and pulmonary functions. Characterizing the asthma endotype and phenotype in patients with severe asthma and determining which treatment would be more appropriate for a particular patient is an essential step in personalized treatment.
Topics: Humans; Anti-Asthmatic Agents; Asthma; Biological Factors; Biological Products; Omalizumab; Quality of Life
PubMed: 37345400
DOI: 10.5578/tt.20239921 -
ERJ Open Research Mar 2023The application of allergen immunotherapy (AIT) in combination with biological agents has been found to increase both the safety and efficacy of the desensitisation...
BACKGROUND
The application of allergen immunotherapy (AIT) in combination with biological agents has been found to increase both the safety and efficacy of the desensitisation procedure in patients with food and insect venom allergy. The aim of our study was to compare the effectiveness of AIT in patients with house dust mite (HDM)-driven asthma treated with and without omalizumab.
MATERIALS AND METHODS
The study was a placebo-controlled, three-armed, randomised, parallel-group, multicentre trial that included 52 patients with HDM-driven asthma. Only patients with monosensitisation to HDM were included. The study compared three patterns of therapy: omalizumab alone, HDM subcutaneous immunotherapy (SCIT-HDM)+ omalizumab, and SCIT alone. The main outcomes were evaluate the Asthma Control Questionnaire (ACQ) score, number of asthma exacerbations and reduction in the daily dose of inhaled steroids during 12 months of observation.
RESULTS
All variants of therapy led to significantly improved ACQ scores and reduction of asthma exacerbations in all study groups after 12 months of treatment. A statistically significant reduction in the daily doses of inhaled corticosteroids in the group with omalizumab alone (650±150 µg 500±50 µg for p=0.003) or SCIT-HDM+omalizumab (550±250 µg 375±75 µg for p=0.001) was observed, favouring the latter group.
CONCLUSION
The efficacy of AIT for HDM-driven asthma is significantly increased by the combination of allergen vaccine with omalizumab.
PubMed: 37077549
DOI: 10.1183/23120541.00639-2022 -
Journal of Thoracic Disease Jun 2023Omalizumab is an effective anti-immunoglobulin E (IgE) treatment for allergic asthma. Eosinophil plays a critical role in the pathogenesis of allergic airway...
BACKGROUND
Omalizumab is an effective anti-immunoglobulin E (IgE) treatment for allergic asthma. Eosinophil plays a critical role in the pathogenesis of allergic airway inflammation. This study aimed to explore the influence of effective omalizumab treatment on circulating eosinophils.
METHODS
Allergic asthmatics enrolled in the study were treated with omalizumab for at least 16 weeks and exhibited a good or excellent response according to the global evaluation of treatment effectiveness (GETE) assessed by each patient and specialist physician. For eosinophil functional evaluation, peripheral blood eosinophils were separated; and examined the expression of human leukocyte antigen (HLA)-DR and co-stimulatory molecules cluster of differentiation (CD) 80, CD86 and CD40 by Flow Cytometry and serum were to measure the concentration of eotaxin-1 before and after 16 weeks of omalizumab treatment.
RESULTS
Totally 32 allergic asthma patients who responded positively to omalizumab treatment were included. Omalizumab responders showed a significant decline in the expression of co-stimulatory molecules CD40, CD80, and CD86 on peripheral eosinophils and in serum eotaxin-1 concentration after treatment. Negative correlations (r=-0.61, P=0.048) were observed between the change in CD80 eosinophils and the change in forced expiratory volume in the first second (FEV1)/forced vital capacity (FVC)% predicted and maximal expiratory flow (MEF) 25% after omalizumab treatment. Omalizumab improved FEV1/FVC% predicted (3.88, P=0.033), fractional exhaled nitric oxide (FeNO, -22.24, P=0.028), asthma control test (ACT, 4.22, P<0.001), mini asthma quality of life questionnaire (mini-AQLQ, -14.44, P=0.019), Leicester cough questionnaire (LCQ, 3.03, P=0.009) and visual analogue scale (VAS) for allergic symptoms (-13.00, P=0.001) in patients with severe allergic asthma statistically; reduced mini rhino-conjunctivitis quality of life questionnaire (mini-RQLQ, -8.50, P=0.047), and self-rating anxiety scale (SAS, -5.08, P=0.040) in allergic asthmatics with concomitant allergic rhinitis (AR) or anxiety, respectively.
CONCLUSIONS
Our findings show a unique role of omalizumab in reducing co-stimulatory molecules expression on eosinophil and serum eotaxin-1 levels in severe allergic asthmatics accompanied by improvement of multiple clinical parameters of allergic diseases.
PubMed: 37426135
DOI: 10.21037/jtd-22-1818 -
Skin Health and Disease Jun 2023Chronic urticaria (CU) is a skin condition driven by mast cells and basophils. The exact responsiveness profile of these cells, especially regarding the anti-IgE...
BACKGROUND
Chronic urticaria (CU) is a skin condition driven by mast cells and basophils. The exact responsiveness profile of these cells, especially regarding the anti-IgE treatment, Omalizumab, is not fully investigated. We sought to characterize the surface activation profile of basophils in CU during Omalizumab treatment and their responsiveness to IgE and non-IgE stimulation.
METHODS
Whole blood basophils from 11 CU patients and 10 healthy controls were stimulated with either medium, anti-IgE, fMLP, C5a, or Substance P for 30 min and characterized by flow cytometry.
RESULTS
CU patients showed a broad range of basophil count as opposed to healthy subjects. An increased number of unstimulated CD69 ( = 0.05), but not CD63 basophils was observed in CU groups in comparison to healthy. The expression of CD203c and CD200R were comparable between all groups, whilst the FcεRI was reduced with the treatment. Both IgE and non-IgE mediated stimulations upregulated CD63, CD203c and CD200R, but not CD69 in all groups, however, no difference between the groups was observed. Among unstimulated basophils, expression of MRGPRX2 was higher in CU patients after Omalizumab treatment than in the healthy group (2.4% vs. 1.5%, = 0.01). The anti-IgE stimulation increased the number of MRGPRX2-expressing basophils in the CU group before and after omalizumab as compared to the healthy ( = 0.003; = 0.005). The fMLP and C5a stimulations showed a similar effect to the IgE-mediated stimulation. The MRGPRX2 ligand, Substance P did not activate basophils.
CONCLUSION
CU basophils show increased expression of MRGPRX2 after IgE and non-IgE stimulation.
PubMed: 37275407
DOI: 10.1002/ski2.195 -
JAMA Dermatology Nov 2021The comparative benefits and harms of all available treatments for H1 antihistamine-refractory chronic spontaneous urticaria (CSU) have not been established. (Meta-Analysis)
Meta-Analysis
IMPORTANCE
The comparative benefits and harms of all available treatments for H1 antihistamine-refractory chronic spontaneous urticaria (CSU) have not been established.
OBJECTIVE
To evaluate different treatment effects of pharmacologic treatments among patients with H1 antihistamine-refractory CSU.
DATA SOURCES
Searches were conducted of MEDLINE, Embase, PubMed, Cochrane Library, Web of Science, Scopus, and CINAHL from inception to April 19, 2021, with no language restrictions. Gray literature from Google Scholar, ongoing trial registers, and preprint reports was added to the searches of electronic databases.
STUDY SELECTION
Randomized clinical trials using validated measurement tools that investigated the benefits and harms of pharmacologic treatments among adolescent or adult patients with CSU who had an inadequate response to H1 antihistamines were screened for inclusion independently by 2 investigators.
DATA EXTRACTION AND SYNTHESIS
Two investigators independently extracted study data according to the predefined list of interests. A random-effects model was used to calculate the network estimates reported as standardized mean differences and odds ratios with corresponding 95% CIs.
MAIN OUTCOMES AND MEASURES
The primary outcomes that reflect the patient's perspective included changes in urticaria symptoms from baseline and unacceptability of treatment (all-cause dropouts).
RESULTS
Twenty-three randomized clinical trials with 2480 participants that compared 18 different interventions or dosages and placebo were included. The standardized mean differences for change in urticaria symptoms were -1.05 (95% CI, -1.37 to -0.73) for ligelizumab, 72 mg; -1.07 (95% CI, -1.39 to -0.75) for ligelizumab, 240 mg; -0.77 (95% CI, -0.91 to -0.63) for omalizumab, 300 mg; and -0.59 (95% CI, -1.10 to -0.08) for omalizumab, 600 mg. No significant differences in treatment unacceptability were observed. With respect to benefits and harms, the network estimates illustrated that the most efficacious treatments were achieved with ligelizumab, 72 or 240 mg (large beneficial effect) and omalizumab, 300 or 600 mg (moderate beneficial effect).
CONCLUSIONS AND RELEVANCE
The findings in this meta-analysis suggest that the biologic agents ligelizumab, 72 or 240 mg, and omalizumab, 300 or 600 mg, can be recommended as effective treatments for patients with CSU who have had an inadequate response to H1 antihistamines. Head-to-head trials with high methodologic quality and harmonized design and outcome definitions are needed to help inform subsequent international guidelines for the management of CSU.
Topics: Adolescent; Adult; Anti-Allergic Agents; Chronic Disease; Chronic Urticaria; Histamine H1 Antagonists; Humans; Network Meta-Analysis; Omalizumab; Treatment Outcome; Urticaria
PubMed: 34431983
DOI: 10.1001/jamadermatol.2021.3237 -
International Journal of... 2023Different monoclonal antibodies have been used for the treatment of Netherton's syndrome (NS); secukinumab (anti-IL17A), infliximab (anti-TNF-α), ustekinumab (anti p40... (Review)
Review
Different monoclonal antibodies have been used for the treatment of Netherton's syndrome (NS); secukinumab (anti-IL17A), infliximab (anti-TNF-α), ustekinumab (anti p40 subunit of IL-12 and IL-23), omalizumab (anti-IgE), and dupilumab (anti-IL4 and IL13). We report two sisters with severe NS who were treated with omalizumab in one and with secukinumab in the other. In view of the therapeutic failure, treatment with dupilumab was started in both sisters. The data were analyzed 16 weeks after starting treatment with dupilumab. Treatment response was assessed using the Severity Scoring Atopic Dermatitis (SCORAD); Eczema Area and Severity Index (EASI); Pruritus Numeric Rating Scale (NSR); Netherton Area Severity Assessment (NASA) and Dermatology Life Quality Index Ichthyosis. All scores were reduced after 16 weeks of treatment with dupilumab in both patients. She maintains improvement after 18 months and 12 months of treatment, respectively. No severe adverse events were reported. Treatment with dupilumab in two sisters with NS and atopic diseases produced a marked cutaneous improvement after a failed attempt with omalizumab and secukinumab. Further studies are needed to determine which biologic therapy is the most effective in NS.
Topics: Female; Humans; Omalizumab; Netherton Syndrome; Tumor Necrosis Factor Inhibitors; Treatment Outcome; Severity of Illness Index; Double-Blind Method
PubMed: 37200480
DOI: 10.1177/03946320231172881 -
Advances in Therapy Jan 2023Omalizumab, a recombinant anti-immunoglobulin E (IgE) monoclonal antibody, is indicated for moderate to severe allergic asthma, chronic spontaneous urticaria, and nasal...
Omalizumab, a recombinant anti-immunoglobulin E (IgE) monoclonal antibody, is indicated for moderate to severe allergic asthma, chronic spontaneous urticaria, and nasal polyps, and is approved for self-administration. However, specific guidance on identifying candidates with characteristics suitable for this type of administration is lacking. To help address this issue, this article provides practical considerations for the health care provider treating patients with omalizumab. We encourage health care providers to consider self-administration of omalizumab as an option for all appropriate, but not all, patients, and we recommend an individualized approach when considering self-administration of omalizumab.
Topics: Humans; Omalizumab; Antibodies, Monoclonal, Humanized; Anti-Allergic Agents; Asthma; Nasal Polyps
PubMed: 36173511
DOI: 10.1007/s12325-022-02308-w -
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 -
Journal of Personalized Medicine Jan 2022Omalizumab is the first monoclonal antibody that was globally approved as a personalized treatment option for patients with moderate-to-severe allergic asthma. This... (Review)
Review
Omalizumab is the first monoclonal antibody that was globally approved as a personalized treatment option for patients with moderate-to-severe allergic asthma. This review summarizes the knowledge of almost two decades of use of omalizumab to answer some important everyday clinical practice questions, concerning its efficacy and safety and its association with other asthma-related and drug-related parameters. Evidence suggests that omalizumab improves asthma control and reduces the incidence and frequency of exacerbations in patients with severe allergic asthma. Omalizumab is also effective in those patients in reducing corticosteroid use and healthcare utilization, while it also seems to improve lung function. Several biomarkers have been recognized in predicting its efficacy in its target group of patients, while the optimal duration for evaluating its efficacy is between 16 and 32 weeks.
PubMed: 35207654
DOI: 10.3390/jpm12020165 -
BMC Pulmonary Medicine Dec 2023A significant breakthrough has been made in treating severe asthma, with the recognition of various asthma phenotypes and an updated management guideline. Type 2...
BACKGROUND
A significant breakthrough has been made in treating severe asthma, with the recognition of various asthma phenotypes and an updated management guideline. Type 2 targeted therapies, such as benralizumab and omalizumab; have been identified as an effective treatment for severe asthma, improving patient response, lung function tests and asthma symptom control. This study aimed to evaluate factors contributing to poor response to therapy.
METHODS
A retrospective single-center cohort study of 162 patients with severe asthma who started biologic therapy; their data were retrieved from medical records for further analysis. Poor responders were patients remained clinically and functionally uncontrolled despite even after augmenting all treatment options.
RESULTS
Childhood-onset asthma, bronchiectasis, poor symptom control (ACT below 19), severe airway obstruction (< 60% predicted), and maintenance oral corticosteroid (mOCS) use were significantly associated with poor response to omalizumab and benralizumab; p = 0.0.4 and 0.01; 0.003 and 0.01; 0.01 and 0.001, 0.05 and 0.04; 0.006 and 0.02, respectively. However, chronic rhinosinusitis and IgE < 220kIU/L were associated with higher poor response rates to omalizumab (p = 0.01 and 0.04, respectively). At the same time, female patients and those with blood eosinophils level < 500 cells/mm3 had a higher poor response rate to benralizumab (p = 0.02 and 0.01, respectively). Ischemic heart disease (IHD), bronchiectasis, and continued use of OCS increased the likelihood of poor response to omalizumab by 21, 7, and 24 times (p = 0.004, 0.008, and 0.004, respectively). In contrast, the female gender, childhood-onset asthma and higher BMI increased the likelihood of poor response to benralizumab by 7, 7 and 2 times more, p = 0.03, 0.02 and 0.05, respectively.
CONCLUSION
Poor response to omalizumab treatment was independently associated with ischemic heart disease (IHD), bronchiectasis, and a history of maintenance oral corticosteroid (mOCS) use. Conversely, poor response to benralizumab therapy was independently linked to female gender, childhood-onset asthma and higher body mass index (BMI).
Topics: Humans; Female; Child; Omalizumab; Anti-Asthmatic Agents; Retrospective Studies; Cohort Studies; Immunoglobulin E; Asthma; Adrenal Cortex Hormones; Bronchiectasis; Myocardial Ischemia
PubMed: 38053108
DOI: 10.1186/s12890-023-02786-w