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Revista Alergia Mexico (Tecamachalco,... Dec 2023Despite promising advancements in oral immunotherapy for food allergies, medical implementation faces limitations. Non-specific treatment options based on inhibiting the...
Despite promising advancements in oral immunotherapy for food allergies, medical implementation faces limitations. Non-specific treatment options based on inhibiting the type 2 inflammatory pathway, including monoclonal antibodies, are under investigation. TNX-901 and omalizumab have demonstrated increased reaction thresholds, reducing adverse events in peanut-allergic patients. Dupilumab, blocking the IL-4 receptor, shows positive results in both food allergies and eosinophilic esophagitis. Antibodies against alarmins and anti-IL-5, such as etokimab and mepolizumab, have proven efficacy in preclinical studies and clinical trials. While further studies are needed to establish their practical clinical use and determine suitability for different types of food allergies, these monoclonal antibodies present a promising horizon for the treatment of such conditions.
Topics: Humans; Biological Products; Antibodies, Monoclonal; Food Hypersensitivity; Immunotherapy; Omalizumab
PubMed: 38506875
DOI: 10.29262/ram.v70i4.1340 -
Revista Alergia Mexico (Tecamachalco,... Dec 2023Food allergy is a common chronic disorder that affects infants, children, adolescents, and adults. The prevalence of food allergy has increased in recent decades...
Food allergy is a common chronic disorder that affects infants, children, adolescents, and adults. The prevalence of food allergy has increased in recent decades throughout the world, not limited to Western countries. Since there is no treatment, this focuses on avoiding allergens, in addition to educating patients and caregivers in the emergency treatment of acute reactions, for example: application of epinephrine. Studies suggest that accidental reactions occur in about 45% of children with food allergies each year, although most reactions are mild or moderate in severity. Hospital admissions for food anaphylaxis vary from 4 to 20 per 100,000 inhabitants; Deaths are rare, with an estimated incidence of 0.03 to 0.3 per million people with food allergy. Death from food anaphylaxis is rare and appears to have remained stable, possibly due to increases in food allergen labeling, diagnostic services, rates of intramuscular epinephrine prescription, and awareness of food allergies. Omalizumab is a drug approved for several disorders (chronic hives or difficult asthma) and may help reduce symptoms associated with food allergy. The relative importance of alternative technologies, management strategies and policies for food allergy varies from one region to another, due to differences in the epidemiology, education, socioeconomic well-being, and cultural preferences of the population.
Topics: Adolescent; Adult; Child; Infant; Humans; Anaphylaxis; Food Hypersensitivity; Asthma; Epinephrine; Omalizumab
PubMed: 38506857
DOI: 10.29262/ram.v70i4.1308 -
BioDrugs : Clinical Immunotherapeutics,... May 2024The management of uncontrolled severe asthma has greatly improved since the advent of novel biologic therapies. Up to August 2022, five biologics have been approved for...
BACKGROUND
The management of uncontrolled severe asthma has greatly improved since the advent of novel biologic therapies. Up to August 2022, five biologics have been approved for the type 2 asthma phenotype: anti-IgE (omalizumab), anti-IL5 (mepolizumab, reslizumab, benralizumab), and anti-IL4 (dupilumab) monoclonal antibodies. These drugs are usually well tolerated, although long-term safety information is limited, and some adverse events have not yet been fully characterized. Spontaneous reporting systems represent the cornerstone for the detection of potential signals and evaluation of the real-world safety of all marketed drugs.
OBJECTIVE
The aim of this study was to provide an overview of safety data of biologics for severe asthma using VigiBase, the World Health Organization global pharmacovigilance database.
METHODS
We selected all de-duplicated individual case safety reports (ICSRs) attributed to five approved biologics for severe asthma in VigiBase, up to 31st August 2022 (omalizumab, mepolizumab, reslizumab, benralizumab and dupilumab). Descriptive frequency analyses of ICSRs were carried out both as a whole class and as individual products. Reporting odds ratios (ROR) with 95% confidence intervals (CIs) were used as the measure of disproportionality for suspected adverse drug reactions (ADRs) associated with the study drugs compared with either all other suspected drugs (Reference Group 1, RG1) or inhaled corticosteroids plus long-acting β-agonists (ICSs/LABAs) (Reference Group 2, RG2) or with oral corticosteroids (OCSs) (Reference Group 3, RG3).
RESULTS
Overall, 31,724,381 ICSRs were identified in VigiBase and 167,282 (0.5%) were related to study drugs; the remaining reports were considered as RG1. Stratifying all biologic-related ICSRs by therapeutic indication, around 29.4% (n = 48,440) concerned asthma use; omalizumab was mainly indicated as the suspected drug (n = 20,501), followed by dupilumab, mepolizumab, benralizumab and reslizumab. Most asthma ICSRs concerned adults (57%) and women (64.1%). Asthma biologics showed a higher frequency of serious suspected ADR reporting than RG1 (41.3% vs 32.3%). The most reported suspected ADRs included asthma, dyspnea, product use issue, drug ineffective, cough, headache, fatigue and wheezing. Asthma biologics were disproportionally associated with several unknown or less documented adverse events, such as malignancies, pulmonary embolism and deep vein thrombosis with omalizumab; alopecia and lichen planus with dupilumab; alopecia and herpes infections with mepolizumab; alopecia, herpes zoster and eosinophilic granulomatosis with polyangiitis related to benralizumab; and alopecia with reslizumab.
CONCLUSIONS
The most frequently reported suspected ADRs of asthma biologics in VigiBase confirmed the presence of well-known adverse effects such as general disorders, injection-site reactions, nasopharyngitis, headache and hypersensitivity, while some others (e.g. asthma reactivation or therapeutic failure) could be ascribed to the indication of use. Moreover, the analysis of signals of disproportionate reporting suggests the presence of malignancies, effects on the cardiovascular system, alopecia and autoimmune conditions, requiring further assessment and investigation.
Topics: Humans; Asthma; Pharmacovigilance; World Health Organization; Anti-Asthmatic Agents; Female; Male; Antibodies, Monoclonal, Humanized; Adverse Drug Reaction Reporting Systems; Databases, Factual; Adult; Biological Therapy; Middle Aged; Aged; Omalizumab; Biological Products
PubMed: 38489062
DOI: 10.1007/s40259-024-00653-6 -
Otolaryngology--head and Neck Surgery :... Jul 2024Provide clinicians with current evidence for biologic therapy in children with chronic rhinosinusitis with nasal polyposis (CRSwNP). (Review)
Review
OBJECTIVE
Provide clinicians with current evidence for biologic therapy in children with chronic rhinosinusitis with nasal polyposis (CRSwNP).
DATA SOURCES
PubMed, MEDLINE, Cochrane, and clinical trial registries.
REVIEW METHODS
Key search terms related to biologic therapy in pediatric CRSwNP were identified via a structured query of current medical literature and clinical trial databases.
CONCLUSIONS
There is a dearth of active clinical trials and research studies for biologics targeting pediatric CRSwNP. There is an ongoing compassionate-use clinical trial involving Dupilumab for children with nasal polyps as well as only 1 published work specifically focused on Dupilumab for pediatric CRSwNP in the setting of aspirin-exacerbated respiratory disease.
IMPLICATIONS FOR PRACTICE
For children with atopic dermatitis, asthma, and chronic idiopathic urticaria, biologic therapies such as Omalizumab, Dupilumab, and Mepolizumab have gained Food and Drug Administration approval. The role of biologic therapy in pediatric CRSwNP demonstrates significant promise in the comprehensive management of the unified airway. Additional Phase III trials are necessary to broaden clinical indications for children with comorbid conditions and complex sinonasal disease.
Topics: Humans; Sinusitis; Chronic Disease; Rhinitis; Child; Biological Therapy; Nasal Polyps; Omalizumab; Rhinosinusitis; Antibodies, Monoclonal, Humanized
PubMed: 38488239
DOI: 10.1002/ohn.717 -
Frontiers in Immunology 2024Hay fever, characterized by seasonal allergic reactions, poses a significant health challenge. Existing therapies encompass standard drug regimens, biological agents,...
BACKGROUND
Hay fever, characterized by seasonal allergic reactions, poses a significant health challenge. Existing therapies encompass standard drug regimens, biological agents, and specific immunotherapy. This study aims to assess and compare the effectiveness of anti-IgE (omalizumab), medication therapy, and subcutaneous immunotherapy (SCIT) for hay fever.
METHODS
Conducted as a retrospective cohort study, this research involved 98 outpatient hay fever patients who underwent routine medication, omalizumab treatment, or SCIT before the onset of the spring pollen season. A follow-up was performed one month after the start of the pollen season. The comprehensive symptoms and drug scores were used to evaluate patients with different intervention methods, facilitating a comparative analysis of therapeutic outcomes.
RESULTS
Compared with before treatment, the symptoms of patients treated with the three methods were all significantly relieved, and the medication score were significantly reduced. Patients treated with omalizumab demonstrated higher symptoms and medication scores than SCIT group before treatment, but similar scores after treatment, which were both lower than medicine treatment group. After treatment with omalizumab or SCIT, patients in both groups had significantly lower medication scores than the medication group and were close to no longer using medication for symptom relief. The mountain juniper-sIgE was significantly higher after treatment than before treatment in both medicine treatment group and omalizumab treatment group.
CONCLUSION
Omalizumab and SCIT offer superior effects than medication therapy in hay fever patients.
Topics: Humans; Omalizumab; Rhinitis, Allergic, Seasonal; Retrospective Studies; Immunosuppressive Agents; Immunotherapy; Antibodies, Anti-Idiotypic
PubMed: 38482006
DOI: 10.3389/fimmu.2024.1363034 -
Annals of Allergy, Asthma & Immunology... May 2024
Topics: Humans; Omalizumab; Food Hypersensitivity; Anti-Allergic Agents; Immunoglobulin E
PubMed: 38479711
DOI: 10.1016/j.anai.2024.03.006 -
Journal of Immunological Methods May 2024Development of assays to reliably identify and characterize anti-drug antibodies (ADAs) depends on positive control anti-idiotype (anti-id) reagents, which are used to...
Development of assays to reliably identify and characterize anti-drug antibodies (ADAs) depends on positive control anti-idiotype (anti-id) reagents, which are used to demonstrate that the standards recommended by regulatory authorities are met. This work employs a set of therapeutic antibodies under clinical development and their corresponding anti-ids to investigate how different positive control reagent properties impact ADA assay development. Positive controls exhibited different response profiles and apparent assay analytical sensitivity values depending on assay format. Neither anti-id affinity for drug, nor sensitivity in direct immunoassays related to sensitivity in ADA assays. Anti-ids were differentially able to detect damage to drug conjugates used in bridging assays and were differentially drug tolerant. These parameters also failed to relate to assay sensitivity, further complicating selection of anti-ids for use in ADA assay development based on functional characteristics. Given this variability among anti-ids, alternative controls that could be employed across multiple antibody drugs were investigated as a more uniform means to define ADA detection sensitivity across drug products and assay protocols, which could help better relate assay results to clinical risks of ADA responses. Overall, this study highlights the importance of positive control selection to reliable detection and clinical interpretation of the presence and magnitude of ADA responses.
Topics: Antibodies, Monoclonal; Immunoassay; Antigens
PubMed: 38479453
DOI: 10.1016/j.jim.2024.113657 -
International Journal of Molecular... Mar 2024The basis of our current understanding of allergies begins with the discovery of IgE in the mid-1960s. The whole theory of the physiology and pathophysiology of allergic... (Review)
Review
The basis of our current understanding of allergies begins with the discovery of IgE in the mid-1960s. The whole theory of the physiology and pathophysiology of allergic diseases, including rhinitis and asthma, dates from that period. Among the key regions of IgE identified were the FAB (fragment antigen binding) portion that has the ability to capture allergens, and the Cε3 domain, through which IgE binds to its membrane receptor. It was then postulated that blocking IgE at the level of the Cε3 domain would prevent it from binding to its receptor and thus set in motion the allergic cascade. This was the beginning of the development of omalizumab, a monoclonal antibody with an anti-IgE effect. In this article, we review the pathophysiology of allergic disease and trace the clinical development of omalizumab. We also review the benefits of omalizumab treatment that are apparently unrelated to allergies, such as its effect on immunity and bronchial remodeling.
Topics: Humans; Omalizumab; Antibodies, Monoclonal, Humanized; Asthma; Hypersensitivity; Immunoglobulin E
PubMed: 38474304
DOI: 10.3390/ijms25053056 -
HNO Jul 2024Chronic rhinosinusitis with nasal polyps (CRSwNP) is a type‑2 inflammatory disease of the upper airways, with severe impairment of quality of life. Persons affected...
BACKGROUND
Chronic rhinosinusitis with nasal polyps (CRSwNP) is a type‑2 inflammatory disease of the upper airways, with severe impairment of quality of life. Persons affected by NSAID-exacerbated respiratory disease (NERD) usually present with highly dynamic recurrence of polyps and disease despite prior treatment with sinus surgeries, oral corticosteroids, and aspirin desensitization (ATAD). Biologic therapy has fundamentally changed the choice of therapeutic concept; however, limited data exist on subgroups such as NERD patients. The aim of the current article is to report on a multicenter retrospective study on add-on therapy with dupilumab, omalizumab, and mepolizumab in patients with NERD.
METHODS
This is a retrospective cohort study of patients (NERD+, status after ATAD) in three reference centers in Germany (Munich, Mainz, Berlin). Subjective and objective parameters were collected at 4, 8, and 12 months after biologic therapy initiation in accordance with current EPOS/EUFOREA (European Position Paper on Rhinosinusitis and Nasal Polyps/European Forum for Research and Education in Allergy and Airway Diseases) guidelines. Biologic agents were chosen depending on availability and patient characteristics.
RESULTS
Treatment was commenced in 122 patients meeting the criteria for CRSwNP and NERD. The endoscopic polyp score, SNOT-22 questionnaire score, visual analogue scoring of total symptoms/severity of disease, and sense of smell (psychophysical testing with Sniffin'Sticks/Brief Smell Identification Test, B‑SIT; Sensonics, Inc., Haddon Heights, NJ, USA) improved significantly after 4 and 12 months of add-on therapy (p < 0.0001). All three biologic agents significantly improved one or more disease parameter. Adverse events were not life threatening but led to change of biologic agent in 4 cases. Patients rated biologic therapy significantly better than ATAD, with improved long-term disease control.
CONCLUSION
Add-on biologic therapy is effective, safe, and widely accepted among CRSwNP + NERD patients. Future studies might allow for personalized algorithms with sequential surgery, ATAD, and/or biologic therapy.
Topics: Humans; Female; Male; Middle Aged; Anti-Inflammatory Agents, Non-Steroidal; Germany; Retrospective Studies; Aspirin; Treatment Outcome; Desensitization, Immunologic; Sinusitis; Adult; Nasal Polyps; Asthma, Aspirin-Induced; Antibodies, Monoclonal, Humanized; Biological Therapy; Rhinitis; Omalizumab; Cohort Studies; Aged; Chronic Disease
PubMed: 38466409
DOI: 10.1007/s00106-024-01433-y -
Allergologia Et Immunopathologia 2024Morbihan syndrome (MS) is characterized by solid facial edema, usually related to rosacea or acne vulgaris. The facial edema deforms the patient's features, can impair... (Review)
Review
Morbihan syndrome (MS) is characterized by solid facial edema, usually related to rosacea or acne vulgaris. The facial edema deforms the patient's features, can impair peripheral vision, and affects quality of life. Its pathophysiology remains unclear. The disease usually has a slow and chronic course. MS most commonly affects middle-aged Caucasian men with rosacea and is rare in people below 20 years of age. MS is a diagnosis of exclusion. There is no standard treatment for MS, though systemic isotretinoin and antihistamines are mainly used. We present the case of an adolescent girl with MS nonresponding to 19 months of isotretinoin treatment with add-on antihistamines. Therapy with monthly administration of omalizumab (anti-IgE) for 6 months was an effective therapeutic option, improving the quality of life. Our case is the second description of omalizumab use in Morbihan syndrome, the first in an adolescent.
Topics: Male; Middle Aged; Female; Humans; Adolescent; Isotretinoin; Omalizumab; Quality of Life; Rosacea; Angioedema; Syndrome; Edema; Histamine Antagonists
PubMed: 38459887
DOI: 10.15586/aei.v52i2.978