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Dermatologic Therapy Jul 2020
Topics: Anti-Allergic Agents; Betacoronavirus; COVID-19; Comorbidity; Coronavirus Infections; Humans; Omalizumab; Pandemics; Pneumonia, Viral; SARS-CoV-2; Urticaria
PubMed: 32510814
DOI: 10.1111/dth.13792 -
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 -
American Journal of Rhinology & Allergy Mar 2023Allergic rhinitis (AR) and chronic rhinosinusitis (CRS) are two prevalent nasal diseases where both type 2 inflammation and immunoglobulin E (IgE) may play important... (Review)
Review
BACKGROUND
Allergic rhinitis (AR) and chronic rhinosinusitis (CRS) are two prevalent nasal diseases where both type 2 inflammation and immunoglobulin E (IgE) may play important roles. Although they can exist independently or comorbidly, subtle but important differences exist in immunopathogenesis.
OBJECTIVE
To summarize current knowledge of pathophysiological roles of B lineage cells and IgE in AR and CRS with nasal polyps (CRSwNP).
METHODS
Searched PubMed database, reviewed AR and CRSwNP-related literature, and discussed disease diagnosis, comorbidity, epidemiology, pathophysiology, and treatment. Similarities and differences in B-cell biology and IgE are compared in the 2 conditions.
RESULTS
Both AR and CRSwNP have evidence for pathological type 2 inflammation, B-cell activation and differentiation, and IgE production. However, distinctions exist in the clinical and serological profiles at diagnosis, as well as treatments utilized. B-cell activation in AR may more frequently be regulated in the germinal center of lymphoid follicles, whereas CRSwNP may occur via extrafollicular pathways although controversies remain in these initial activating events. Oligoclonal and antigen-specific IgE maybe predominate in AR, but polyclonal and antigen-nonspecific IgE may predominate in CRSwNP. Omalizumab has been shown efficacious in treating both AR and CRSwNP in multiple clinical trials but is the only Food and Drug Administration-approved anti-IgE biologic to treat CRSwNP or allergic asthma. frequently colonizes the nasal airway and has the ability to activate type two responses including B-cell responses although the extent to which it modulates AR and CRSwNP disease severity is being investigated.
CONCLUSION
This review highlights current knowledge of the roles of B cells and IgE in the pathogenesis of AR and CRSwNP and a small comparison between the 2 diseases. More systemic studies should be done to elevate the understanding of these diseases and their treatment.
Topics: United States; Humans; Immunoglobulin E; Omalizumab; Rhinitis, Allergic; B-Lymphocytes; Inflammation
PubMed: 36848269
DOI: 10.1177/19458924221147770 -
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 -
Medicine May 2023Approximately 1-third of patients with severe asthma are candidates for both omalizumab and mepolizumab treatment. We aimed to compare the clinical, spirometric and... (Observational Study)
Observational Study
Comparison of omalizumab and mepolizumab treatment efficacy in patients with atopic and eosinophilic "Overlap" severe asthma: Biological agent preference in atopic-eosinophilic severe asthma.
Approximately 1-third of patients with severe asthma are candidates for both omalizumab and mepolizumab treatment. We aimed to compare the clinical, spirometric and inflammatory efficacy of these 2 biologics in atopic and eosinophilic "overlap" severe asthma patients. In our 3-center retrospective cross-sectional observational study, the data of patients who received omalizumab or mepolizumab for at least 16 weeks to treat severe asthma were examined. Atopic (perennial allergen sensitivity and total IgE level 30-1500 IU/mL) and eosinophilic (blood eosinophil counts ≥150 cells/µL in admission; or ≥300 cells/µL in the previous year) patients with asthma suitable for both biologics were included in the study. Post-treatment changes in the asthma control test (ACT) score, number of attacks, forced expiratory volume in 1 second (FEV1), and eosinophil count were compared. The rates of any biological responder patient were compared according to whether they had high eosinophil counts (≥500 cells/µL vs <500 cells/µL). Total of 181 patients data were evaluated, of the 74 atopic and eosinophilic overlap patients included in the study, 56 were receiving omalizumab and 18 were receiving mepolizumab. When omalizumab and mepolizumab treatment efficacies were compared, there was no difference in terms of the reduction in attacks and improvement in ACT. The decrease in eosinophil levels in patients in the mepolizumab arm was significantly higher than that in patients in the omalizumab arm (46.3% vs 87.8%; P < .001). The improvement in FEV1 was greater with mepolizumab treatment, although the difference was not significant (215 mL vs 380 mL; P = .053). It has been shown that having high eosinophil counts does not affect the clinical and spirometric responder patient rates for either biological condition. The success of omalizumab and mepolizumab treatment is similar in patients with atopic and eosinophilic overlap with severe asthma. However, because the baseline patient inclusion criteria are not compatible, head-to-head studies comparing both biological agents are required.
Topics: Humans; Omalizumab; Anti-Asthmatic Agents; Biological Factors; Retrospective Studies; Cross-Sectional Studies; Asthma; Pulmonary Eosinophilia; Treatment Outcome; Biological Products
PubMed: 37144999
DOI: 10.1097/MD.0000000000033660 -
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 -
The Journal of Allergy and Clinical... Nov 2021Higher asthma burden is more likely to be experienced by Black than White patients. In clinical research, underrepresentation of minority populations is observed.
BACKGROUND
Higher asthma burden is more likely to be experienced by Black than White patients. In clinical research, underrepresentation of minority populations is observed.
OBJECTIVE
To estimate response to omalizumab in Black and White patients in North America with moderate to severe asthma.
METHODS
Data from placebo-controlled (EXTRA) and single-armed (PROSPERO) omalizumab studies were used for this post hoc analysis. We used a Poisson regression model to examine exacerbation rates. An analysis of covariance model was used to estimate placebo-corrected change in FEV and Asthma Quality of Life Questionnaire (AQLQ) by racial group.
RESULTS
This analysis included 631 White and 176 Black patients from EXTRA and 567 White and 130 Black patients from PROSPERO. In EXTRA, placebo-corrected exacerbation rate reductions (relative rate change [95% confidence interval], 22.6% [2.0-38.9%] vs 22.0% [-18.0% to 48.4%]) and FEV improvements were similar for White and Black patients. There was a trend toward greater AQLQ improvements for Black versus White patients (least squares mean treatment differences: 0.0 vs 0.3, 0.6 vs 0.4, and 0.6 vs 0.2 at weeks 16, 32, and 48, respectively) throughout the study. In PROSPERO, on-study exacerbation rates (0.76 [0.65-0.88] vs 0.77 [0.56-1.10]) and AQLQ improvements (least squares mean change from baseline: 1.2 vs 1.2 and 1.3 vs 1.2 at month 6 and end of study, respectively) were similar for White versus Black patients. A trend toward greater FEV improvement was observed in White versus Black patients throughout the study.
CONCLUSIONS
This analysis of EXTRA and PROSPERO suggests that Black and White patients with moderate to severe asthma experience similar improvements in exacerbations, FEV, and AQLQ with omalizumab.
Topics: Anti-Asthmatic Agents; Asthma; Humans; Omalizumab; Quality of Life; Treatment Outcome
PubMed: 34303017
DOI: 10.1016/j.jaip.2021.07.013 -
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 -
The Yale Journal of Biology and Medicine Jun 2022: Omalizumab has been demonstrated to be effective in treating chronic spontaneous urticaria (CSU) and was FDA approved for this indication in 2014. Previous work has...
: Omalizumab has been demonstrated to be effective in treating chronic spontaneous urticaria (CSU) and was FDA approved for this indication in 2014. Previous work has shown that access to injectable biologics varies across US counties. In the present study we evaluate geographic and temporal trends in the utilization of omalizumab in the Medicare population by dermatologists, with its use by allergists and pulmonologists as comparators. : We analyzed year-over-year trends in omalizumab utilization across geographic regions using the Medicare Provider Utilization and Payment Data: Part D files. : Utilization of omalizumab by dermatologists increased rapidly after its FDA approval, from 0.08 claims/100,000 enrollees totaling $209/100,000 enrollees in 2014 to 1.45 claims/100,000 enrollees totaling $3115/100,000 enrollees in 2017. Nonetheless, prescribing dermatologists were present in only 2.8% (95% Confidence Interval (CI): 2.0%-3.9%) and 0.2% (95% CI: 0.0%-0.5%) of metropolitan and non-metropolitan counties, respectively, in 2017, demonstrating limited availability, especially in non-metropolitan counties. Similarly, prescribers of any specialty were available in 32.9% (95% CI: 30.2%-35.6%) and 3.8% (95% CI: 3.1%-4.8%) of metropolitan and non-metropolitan counties, respectively, in 2017. : Our data suggest that despite increasing omalizumab utilization, there remains a lack of access across many counties, particularly in non-metropolitan regions. Efforts to expand omalizumab prescriber accessibility in these counties may improve outcomes for patients with CSU.
Topics: Aged; Biological Products; Drug Costs; Humans; Medicare; Omalizumab; United States; Urticaria
PubMed: 35782473
DOI: No ID Found -
Actas Dermo-sifiliograficas Jun 2023Recent guideline on the management of urticaria recommends second-generation H1-antihistamine as the first-line therapy, with dose increases of up to fourfold if... (Review)
Review
Recent guideline on the management of urticaria recommends second-generation H1-antihistamine as the first-line therapy, with dose increases of up to fourfold if inadequately controlled. However, the treatment of chronic spontaneous urticaria (CSU) is often disappointing, so additional adjuvant therapies are needed to increase the effectiveness of first-line therapy, especially in patients who are refractory to the increase of antihistamine doses. Recent studies recommend various adjuvant therapy modalities for CSU, such as biological agents, immunosuppressants, leukotriene receptor antagonists, H2-antihistamine, sulfones, autologous serum therapy, phototherapy, vitaminD, antioxidants, and probiotics. This literature review was made to determine the effectiveness of various adjuvant therapies in managing CSU.
Topics: Humans; Chronic Disease; Chronic Urticaria; Urticaria; Histamine H1 Antagonists; Combined Modality Therapy; Omalizumab
PubMed: 37172893
DOI: 10.1016/j.ad.2023.05.008