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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 -
BMJ (Clinical Research Ed.) Mar 2024
Topics: Humans; Omalizumab; Food Hypersensitivity; Desensitization, Immunologic
PubMed: 38453181
DOI: 10.1136/bmj.q547 -
Allergy and Asthma Proceedings Mar 2024Omalizumab is approved for the treatment of chronic spontaneous urticaria (CSU) that is refractory to antihistamines. Total immunoglobulin E (IgE) levels have emerged... (Meta-Analysis)
Meta-Analysis
Omalizumab is approved for the treatment of chronic spontaneous urticaria (CSU) that is refractory to antihistamines. Total immunoglobulin E (IgE) levels have emerged as a possible biomarker to predict response to omalizumab. However, the existing literature is heterogenous, with conflicting conclusions with regard to the role of total IgE levels. We sought to clarify the role of evaluating total IgE levels in patients with CSU by performing a meta-analysis on the existing literature to determine if meaningful changes exist between responders and nonresponders to omalizumab. A total of 68 unique citations were returned and screened by two independent reviewers. Editorials, reviews, and case reports were excluded, and a total of 33 original articles were identified and underwent secondary evaluation. Studies that present mean ± standard deviation total IgE levels and/or 95% confidence intervals (CI) were included, whereas studies with < 25 subjects were excluded. Three studies ultimately met these criteria. We found a mean difference in total IgE levels between those who responded to omalizumab versus those without a response of 49.76 (95% CI, 7.13-92.38; p = 0.02), which demonstrated higher mean IgE values in responders compared with nonresponders. This study presents additional evidence that supports evaluation of total IgE levels as it pertains to response to omalizumab therapy in CSU. When considering the current evidence, it seems reasonable to consider the baseline total IgE level as a biomarker to predict the treatment response to omalizumab. Based on the existing literature, we cannot conclude at what threshold nonresponse is more likely to occur.
Topics: Humans; Omalizumab; Chronic Urticaria; Biomarkers; Immunologic Tests; Immunoglobulin E
PubMed: 38449010
DOI: 10.2500/aap.2024.45.230092 -
Respiratory Medicine 2024In asthma, inflammation affects both the proximal and distal airways and can cause significant hyperinflation, which is thought to be a major cause of dyspnea. (Observational Study)
Observational Study
BACKGROUND
In asthma, inflammation affects both the proximal and distal airways and can cause significant hyperinflation, which is thought to be a major cause of dyspnea.
METHODS
This is a retrospective observational study evaluating the effect of three months of treatment with different biologic drugs (benralizumab, dupilumab and omalizumab) on pulmonary hyperinflation in a cohort of patients with severe asthma already receiving regular triple inhaled therapy. Changes in RV, RV/TLC ratio, FRC and FRC/TLC ratio were the primary efficacy measures. Secondary outcomes included FEV, FVC, FEV/FVC ratio, IC, IC/TLC ratio, asthma control test, the percentage of eosinophils in the blood and fractional F.
RESULTS
Benralizumab led to significant changes (p < 0.001) in RV, RV/TLC, FRC, and FRC/TLC. Dupilumab demonstrated a notable reduction in RV (p = 0.017) and RV/TLC (p = 0.002), but the decreases in FRC and FRC/TLC were merely numerical and not as pronounced as those induced by benralizumab. Omalizumab's positive impact on RV (p = 0.057) and RV/TLC (p = 0.085), as well as FRC (p = 0.202) and FRC/TLC (p = 0.096), was also predominantly numerical, with a tendency towards efficacy, albeit excluding the effect on FRC. Treatment with biologics resulted in improvements in all other lung function parameters assessed and a decrease in F levels.
CONCLUSION
This study, although limited by small sample size, lack of a placebo control, and unbalanced group sizes, suggests that biological agents are effective in reducing lung hyperinflation even after a relatively short treatment.
Topics: Humans; Biological Products; Omalizumab; Forced Expiratory Volume; Asthma; Lung
PubMed: 38431058
DOI: 10.1016/j.rmed.2024.107578 -
Molecular Pharmaceutics Apr 2024In the clinical application of freeze-dried highly concentrated omalizumab formulations, extensive visible bubbles (VBs) can be generated and remain for a long period of...
In the clinical application of freeze-dried highly concentrated omalizumab formulations, extensive visible bubbles (VBs) can be generated and remain for a long period of time in the reconstitution process, which greatly reduces the clinical use efficiency. It is necessary to understand the forming and breaking mechanism of VBs in the reconstitution process, which is a key factor for efficient and safe administration of biopharmaceutical injection. The effects of different thermal treatments on the volume of VBs and stability of omalizumab, mAb-1, and mAb-2 were investigated. The internal microvoids of the cake were characterized by scanning electron microscopy and mercury intrusion porosimetry. Electron paramagnetic resonance was applied to obtain the molecular mobility of the protein during annealing. A large number of VBs were generated in the reconstitution process of unannealed omalizumab and remained for a long period of time. When annealing steps were added, the volume of VBs was dramatically reduced. When annealed at an aggressive temperature (i.e., -6 °C), although the volume of VBs decreased, the aggregation and acidic species increased significantly. Thus, our observations highlight the importance of setting an additional annealing step with a suitable temperature, which contributes to reducing the VBs while maintaining the stability of the high concentration freeze-dried protein formulation.
Topics: Omalizumab; Temperature; Proteins; Freeze Drying; Drug Stability
PubMed: 38430187
DOI: 10.1021/acs.molpharmaceut.3c00991 -
Dermatologie (Heidelberg, Germany) Apr 2024International guidelines for the treatment of chronic spontaneous urticaria support the updosing of second-generation antihistamines to four times of the approved dose... (Review)
Review
International guidelines for the treatment of chronic spontaneous urticaria support the updosing of second-generation antihistamines to four times of the approved dose when adequate symptom control cannot be achieved with the standard dosage. However, this recommendation is primarily based on expert opinions, and there is a lack of large, well-designed, double-blind clinical trials. Most the existing trials provide insufficient data, and due to the heterogeneity of the conducted trials on antihistamine effects (definition of control, design, quality, lack of an active comparator, no placebo arm, small sample size, outcomes) and their short duration, comparative analysis is challenging. However, it can be concluded that the use of modern second-generation antihistamines is both effective and safe based on the available data and our own long-term experiences in the specialized outpatient clinic of a university dermatology department, even though increased dosages (up to fourfold as per the current international guidelines) may be necessary for symptom control. Another therapeutic option for refractory symptoms in chronic spontaneous urticaria is subcutaneous administration of omalizumab at a dosage of 300 mg at 4‑week intervals as a very safe and effective treatment.
Topics: Humans; Chronic Disease; Urticaria; Omalizumab; Histamine H1 Antagonists; Chronic Urticaria; Histamine H1 Antagonists, Non-Sedating; Pruritus; Randomized Controlled Trials as Topic
PubMed: 38427051
DOI: 10.1007/s00105-024-05315-w -
The Journal of Allergy and Clinical... Jun 2024Biologic modifiers targeting type 2 (T2) airway inflammation are effective in reducing asthma exacerbation. However, real-world and comparative effectiveness studies... (Comparative Study)
Comparative Study
BACKGROUND
Biologic modifiers targeting type 2 (T2) airway inflammation are effective in reducing asthma exacerbation. However, real-world and comparative effectiveness studies remain limited.
OBJECTIVE
To examine and compare the real-world impact of anti-T2 asthma biologics.
METHODS
In this retrospective, new user cohort study, we used the MarketScan, a Commercial Claims and Encounters Database, to identify adult patients with asthma who began to receive an anti-T2 biologic agent (anti-IL-5s, dupilumab, or omalizumab). We examined the influence of the biologic class on asthma exacerbation by comparing the average number of asthma exacerbation 1 year before and after biologic initiation. We conducted multivariable regression analyses to compare the effectiveness of these asthma biologics on reducing the incidence of asthma exacerbations within 18 months of the initial administration of biologics while controlling for demographic variables, comorbidities, and asthma severity.
RESULTS
We identified 5,538 asthma patients who were new to taking an anti-T2 biologic [mean age [±SD], 45.6 (12.78) years; 65.8% female). Asthma biologics reduced asthma exacerbation by 11% to 47%, particularly among patients with two or more asthma exacerbations in the year preceding biologic initiation (31% to 65% reduction). Biologics were especially effective in reducing asthma-related hospitalizations (44.6% to 60%). After adjusting for baseline demographics, asthma medication, and comorbidities, dupilumab was associated with a lower estimated mean number of asthma exacerbation per year and lower adjusted odds ratio for developing an asthma exacerbation relative to other biologics (50% to 80% less likely).
CONCLUSIONS
Anti-T2 asthma biologics reduced asthma exacerbation in real-word settings. Evidence supports growing literature reporting that dupilumab might have a more favorable impact on asthma exacerbation relative to other asthma biologics.
Topics: Humans; Asthma; Female; Male; Middle Aged; Adult; Biological Products; Anti-Asthmatic Agents; United States; Retrospective Studies; Antibodies, Monoclonal, Humanized; Omalizumab; Disease Progression
PubMed: 38423294
DOI: 10.1016/j.jaip.2024.02.029 -
Nature Mar 2024
Topics: Humans; Asthma; Food Hypersensitivity; Injections; Omalizumab
PubMed: 38409406
DOI: 10.1038/d41586-024-00586-8