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Italian Journal of Pediatrics Nov 2019Severe asthma has a substantial epidemiological impact on children and biological treatments can be an option to take into account, as they target specific molecules and... (Review)
Review
Severe asthma has a substantial epidemiological impact on children and biological treatments can be an option to take into account, as they target specific molecules and pathways involved in its pathogenesis. Modern medicine is continuously and progressively oriented towards tailored treatments designed specifically for the pathology patterns observed in individual patients and identified as endotypes with associated biomarkers. In this regard, biologic treatments in asthma are one of the best examples. Among the biological drugs currently available, omalizumab is the one with the greatest amount of data on efficacy and safety, and the one we have more real-life clinical experience with. However, mepolizumab will likely be accessible soon globally for clinical use. Moreover, research on biological drugs for the treatment of severe asthma is expanding rapidly, with some molecules currently used in adult patients that could be registered also for pediatric use and new molecules that could be available in the future. On the other hand, due to this potential abundance of therapeutic options, new criteria could become necessary to guide clinicians through an evidence-based choice between omalizumab and these new drugs. For the same reason, more data collected specifically from pediatric clinical trials are necessary. In this review we aim to analyze the factors that could help clinicians make their choice and to highlight the unmet need for a more evidence-based choice.
Topics: Anti-Asthmatic Agents; Antibodies, Monoclonal, Humanized; Asthma; Biological Products; Child; Humans; Omalizumab
PubMed: 31779657
DOI: 10.1186/s13052-019-0737-4 -
Scientific Reports Feb 2015Currently, limited information is available to clinicians regarding the long-term efficacy of omalizumab treatment for allergic asthma. In this report, we aimed to (i)... (Meta-Analysis)
Meta-Analysis Review
Currently, limited information is available to clinicians regarding the long-term efficacy of omalizumab treatment for allergic asthma. In this report, we aimed to (i) systematically review the evidence regarding the long-term efficacy of omalizumab in patients with persistent uncontrolled allergic asthma, and to (ii) discuss the cost-effectiveness evidence published for omalizumab in this patient population. A comprehensive search for randomized controlled trials (RCTs; ≥52 weeks) was performed, and six studies met our final inclusion criteria (n = 2,749). Omalizumab was associated with significant improvements in quality of life and the Global Evaluation of Treatment Effectiveness. Omalizumab also allowed patients to completely withdraw from inhaled corticosteroid therapy and did not increase the overall incidence of adverse events. However, there was insufficient evidence that omalizumab reduced the incidence of exacerbations, and the cost-effectiveness of omalizumab varied across studies. Our data indicated that omalizumab use for at least 52 weeks in patients with persistent uncontrolled allergic asthma was accompanied by an acceptable safety profile, but it lacked effect on the asthma exacerbations. Use of omalizumab was associated with a higher cost than conventional therapy, but these increases may be cost-effective if the medication is used in patients with severe allergic asthma.
Topics: Age Factors; Anti-Allergic Agents; Asthma; Clinical Trials as Topic; Databases, Factual; Humans; Omalizumab; Severity of Illness Index; Treatment Outcome
PubMed: 25645133
DOI: 10.1038/srep08191 -
Journal of Dermatological Science Jul 2017Many patients with chronic spontaneous/idiopathic urticaria (CSU/CIU) do not respond adequately to treatment with non-sedating H1 antihistamines (H1AH). There are... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Many patients with chronic spontaneous/idiopathic urticaria (CSU/CIU) do not respond adequately to treatment with non-sedating H1 antihistamines (H1AH). There are limited studies on use of omalizumab as add-on therapy for treatment of CSU in an Asian population.
OBJECTIVE
The POLARIS study (NCT02329223), representing the first randomized, double-blind, placebo-controlled phase III trial of omalizumab for CSU in an Eastern Asian population, evaluated efficacy and safety of omalizumab as add-on therapy for treatment of CSU.
METHODS
This 26-week multicenter (41 Japanese/Korean sites) study enrolled patients (12-75 years) who were symptomatic despite H1AH treatment. Eligible participants (N=218) were randomized 1:1:1 to receive three subcutaneous injections of omalizumab 300mg, 150mg, or placebo every 4 weeks, followed by 12 weeks of follow-up. Primary outcome was change from baseline to Week 12 (Wk12) in weekly itch severity score (ISS7). Safety was assessed through the summary of adverse events (AEs).
RESULTS
Baseline demographics and disease characteristics were generally well balanced across treatment groups. At Wk12, statistically significant decreases from baseline were observed in ISS7 with omalizumab vs placebo (mean changes -10.22, -8.80, and -6.51 for omalizumab 300mg, 150mg and placebo; p<0.001 and p=0.006 vs placebo, respectively). Overall AE incidence was similar across treatment groups (54.8%, 57.7%, and 55.4% in omalizumab 300mg, 150mg, and placebo groups, respectively); nasopharyngitis was the most frequently reported AE in all treatment arms.
CONCLUSION
The POLARIS study demonstrates that omalizumab is an efficacious and well-tolerated add-on therapy in Japanese and Korean H1AH-refractory patients with CSU.
Topics: Adult; Chronic Disease; Double-Blind Method; Female; Humans; Male; Middle Aged; Omalizumab; Urticaria
PubMed: 28366435
DOI: 10.1016/j.jdermsci.2017.03.009 -
Indian Journal of Dermatology,... 2021Autoimmune bullous diseases can be intraepidermal (pemphigus group of disorders) or subepidermal (pemphigoid group of disorders). The treatment of these disorders... (Review)
Review
Autoimmune bullous diseases can be intraepidermal (pemphigus group of disorders) or subepidermal (pemphigoid group of disorders). The treatment of these disorders chiefly comprises corticosteroids and immunosuppressant adjuvants like azathioprine and mycophenolate mofetil. Autoantibodies are the main mediators of these diseases. Rituximab, a chimeric anti-CD20 monoclonal antibody targeting B-cells, has emerged as an excellent treatment option for refractory pemphigus vulgaris in the last decade. Since then, many new biologics have been proposed/explored for managing autoimmune bullous diseases. These hold potential for greater efficacy and lesser adverse effects than conventional immunosuppressants. In this review, we discuss the role of various biologics in the treatment of autoimmune bullous diseases, followed by a brief discussion on the drawbacks to their use and new developments in this area.
Topics: Antibodies, Monoclonal, Humanized; Autoantibodies; Autoimmune Diseases; Biosimilar Pharmaceuticals; Dose-Response Relationship, Drug; Enzyme Inhibitors; Humans; Immunoglobulins, Intravenous; Omalizumab; Protein-Tyrosine Kinases; Skin Diseases, Vesiculobullous; T-Lymphocytes
PubMed: 34245525
DOI: 10.25259/IJDVL_886_19 -
The Journal of Allergy and Clinical... Oct 2022Nonsteroidal anti-inflammatory drug-exacerbated respiratory disease (N-ERD) is a condition characterized by the triad of chronic rhinosinusitis with nasal polyps,... (Review)
Review
Nonsteroidal anti-inflammatory drug-exacerbated respiratory disease (N-ERD) is a condition characterized by the triad of chronic rhinosinusitis with nasal polyps, bronchial asthma, and hypersensitivity to nonsteroidal anti-inflammatory drugs. This article explores the current knowledge on the various pathological mechanism(s) of N-ERD-such as arachidonic acid metabolism, cysteinyl leukotrienes, prostaglandins, platelets, IgE, mast cells, eosinophils, basophils, and innate immune system-and the role of omalizumab in its management. The authors dive deep into the role of IgE in N-ERD and its potential as a therapeutic target. IgE plays a significant role in mediating allergic reactions, is intricately linked with mast cells, interacts with multiple immunopathological pathways involved in N-ERD, and tends to be elevated in patients with N-ERD. Multiple real-world studies, observational studies, and case series, as well as 2 phase III trials, have demonstrated the effectiveness of omalizumab in the management of N-ERD. For a disease with such a well-documented history, the pathophysiology of N-ERD and the most effective ways to manage it remain a mystery. With this background, the authors ask-is IgE a missing piece of the N-ERD puzzle, thus explaining the efficacy of omalizumab in the treatment of the disease?
Topics: Anti-Inflammatory Agents, Non-Steroidal; Arachidonic Acid; Humans; Hypersensitivity; Immunoglobulin E; Leukotrienes; Omalizumab; Prostaglandins; Respiration Disorders
PubMed: 35764285
DOI: 10.1016/j.jaip.2022.06.016 -
Immunopharmacology and Immunotoxicology Jun 2021Coronavirus disease 2019 (COVID-19) is associated with irreversible effects on vital organs, especially the respiratory and cardiac systems. While the immune system... (Review)
Review
Coronavirus disease 2019 (COVID-19) is associated with irreversible effects on vital organs, especially the respiratory and cardiac systems. While the immune system plays a key role in the survival of patients to viral infections, in COVID-19, there is a hyperinflammatory immune response evoked by all the immune cells, such as neutrophils, monocytes, and includes release of various cytokines, resulting in an exaggerated immune response, named cytokine storm. This severe, dysregulated immune response causes multi-organ damage, which eventually leads to high mortality. One of the most important components of hypersensitivity is immunoglobulin E (IgE), which plays a major role in susceptibility to respiratory infections and can lead to the activation of mast cells. There is also a negative association between IgE and IFN-α, which can reduce Toll-like receptor (TLR) nine receptor expression and TLR-7 signaling to disrupt IFN production. Moreover, anti-IgE drugs such as omalizumab reduces the severity and duration of COVID-19. In addition to its anti-IgE effect, omalizumab inhibits inflammatory cells such as neutrophils. Hence, blockade of IgE may have clinical utility as an immunotherapy for COVID-19.
Topics: COVID-19; Humans; Immunoglobulin E; Interferon-alpha; Omalizumab; Signal Transduction; Toll-Like Receptor 7; COVID-19 Drug Treatment
PubMed: 34018464
DOI: 10.1080/08923973.2021.1925906 -
Medical Principles and Practice :... 2023The objective of this study was to assess the effectiveness of switching from omalizumab to another biologic therapy for patients with severe asthma and evaluate factors...
OBJECTIVE
The objective of this study was to assess the effectiveness of switching from omalizumab to another biologic therapy for patients with severe asthma and evaluate factors that influenced the decision to switch and determined the optimal time for a good biologic response.
SUBJECTS AND METHODS
A retrospective study of severe asthma patients was conducted at Al-Rashed Allergy Center, a tertiary center in Kuwait. After meeting the eligibility criteria, patients were divided into two comparative groups: those continuing with omalizumab and those who started with omalizumab but switched to another biologic.
RESULTS
One hundred sixteen patients with severe asthma were recruited, and only 33 had access to multiple biological treatments. Approximately 22.4% switched from omalizumab. Male patients with a history of ischemic heart disease, chronic rhinosinusitis, and nasal polyps were more likely to switch if they had higher levels of eosinophils in the sputum. This study showed that every 1% increase in sputum eosinophils doubled the likelihood of a switch. Patients with access to alternative biological options had a much shorter mean duration of omalizumab therapy before switching compared to those with only affordable omalizumab: 4.9 ± 1.5 years versus 8.9 ± 1.3 years (p < 0.001). The optimal time to predict the likelihood of a good response was less than 5.5 years, with an area under the curve of 0.91 and p = 0.003. This cutoff point provided a sensitivity and specificity of approximately 89% and 100%, respectively.
CONCLUSION
An early transition from omalizumab, specifically within the first 5 years of treatment, in patients with severe asthma and higher sputum eosinophils may enhance the likelihood of a good response if other biological therapies were available.
Topics: Humans; Male; Omalizumab; Anti-Asthmatic Agents; Retrospective Studies; Asthma; Biological Products; Treatment Outcome
PubMed: 37757780
DOI: 10.1159/000534319 -
Scientific Reports Oct 2023Asthma is a chronic inflammatory condition that affects the lung airways. Chronic use of oral glucocorticoids in patients with severe asthma is associated with several...
Asthma is a chronic inflammatory condition that affects the lung airways. Chronic use of oral glucocorticoids in patients with severe asthma is associated with several adverse events (AEs). Biologics (omalizumab, benralizumab, mepolizumab, reslizumab, and dupilumab) have been developed as alternative therapies for the treatment of asthma. In this study, we aimed to evaluate the risk of anaphylactic reactions associated with these five biologics based on a large global database. We utilized individual case reports from the Uppsala Monitoring Center from January 1968 to December 29, 2019. A disproportionality analysis was performed over all drugs and monoclonal antibodies. Anaphylactic reactions were defined according to the "anaphylactic reaction" of the standardized MedDRA queries. Contrary to dupilumab, omalizumab, benralizumab, and mepolizumab demonstrated positive signals related to anaphylactic reactions over all drugs and monoclonal antibodies. Reslizumab, which represented only 315 cases of all AEs, requires more reports to determine its association with anaphylactic reactions. More anaphylactic reactions have been identified than are known, and most cases (96.2%) are reported to be serious. Our findings indicate that omalizumab, benralizumab, and mepolizumab for asthma treatment are associated with a high risk of anaphylactic reactions; thus, more careful monitoring in the post-administration period is recommended.
Topics: Humans; Omalizumab; Anti-Asthmatic Agents; Biological Products; Pharmacovigilance; Anaphylaxis; Asthma; Antibodies, Monoclonal
PubMed: 37848636
DOI: 10.1038/s41598-023-44973-z -
CPT: Pharmacometrics & Systems... Jun 2023The pharmacokinetic (PK) characteristics of omalizumab and its pharmacodynamic (PD) effect in patients has yet to be fully characterized in chronic spontaneous...
The pharmacokinetic (PK) characteristics of omalizumab and its pharmacodynamic (PD) effect in patients has yet to be fully characterized in chronic spontaneous urticaria, which could elucidate its pathogenesis and treatment response. This study has two objectives; (1) characterize the population PK of omalizumab and its PD effect on IgE, and (2) develop a drug effect model of omalizumab in urticaria (via change in weekly itch severity score). The target-mediated population of PK/PD model incorporating omalizumab-IgE binding and turnover adequately described PK and PD of omalizumab. The effect compartment model and linear drug effect and additive placebo response adequately described placebo and treatment effects of omalizumab. Several baseline covariates were identified for PK/PD and drug effect models. The developed model has the potential to aid in understanding variability in PK/PD as well as response to omalizumab treatment.
Topics: Humans; Omalizumab; Anti-Allergic Agents; Chronic Disease; Chronic Urticaria; Immunoglobulin E; Treatment Outcome
PubMed: 36896910
DOI: 10.1002/psp4.12953 -
Asian Pacific Journal of Allergy and... Sep 2014Allergen avoidance is the standard treatment for managing food allergies. Complete avoidance is difficult, and accidental exposure often occurs. Immunotherapy is a... (Review)
Review
Allergen avoidance is the standard treatment for managing food allergies. Complete avoidance is difficult, and accidental exposure often occurs. Immunotherapy is a significant focus for treating food allergies, and oral immunotherapy (OIT) appears to be particularly effective in inducing desensitization. The majority of patients who receive OIT show increased threshold doses of their food allergen. The efficacy of OIT is different among food antigen, and milk OIT is relatively difficult to achieve tolerance. OIT may induce mild to moderate symptoms during the therapy, widespread acceptance of OIT for long-term therapy is unclear. Recently, novel immunotherapies for food allergies, such as sublingual immunotherapy (SLIT), and epicutaneous immunotherapy (EPIT) and using an anti-IgE monoclonal antibody (omalizumab), have been assessed. In addition, a combination of OIT with omalizumab, which was found to increase the threshold doses of the offending foods without producing adverse reactions, may be effective and useful in the treatment of food allergies. These treatments have been used only in research settings; further studies in large numbers of patients are needed to demonstrate their long-term safety and benefits in clinical practice.
Topics: Animals; Anti-Allergic Agents; Antibodies, Anti-Idiotypic; Antibodies, Monoclonal, Humanized; Antigens; Desensitization, Immunologic; Food Hypersensitivity; Humans; Immune Tolerance; Omalizumab
PubMed: 25268336
DOI: No ID Found