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Current Allergy and Asthma Reports Dec 2023Chronic spontaneous urticaria and chronic inducible urticaria (CSU/CindU) are caused by mast cell and basophil activation leading to degranulation and the release of... (Review)
Review
PURPOSEOF REVIEW
Chronic spontaneous urticaria and chronic inducible urticaria (CSU/CindU) are caused by mast cell and basophil activation leading to degranulation and the release of histamine and several other mediators. Three kinds of factors can trigger mast cells in CSU: (1) activation of stimulating receptor(s) on the mast cell membrane, (2) upregulation of certain receptor(s), and (3) intracellular dysregulation in signaling with overexpression of the spleen tyrosine kinase (SYK) or reduced activation of the inhibitory Src homology 2 (SH2)-containing inositol phosphatases (SHIP)-related pathways. In CSU, two major endotypes exist based on the primary receptor activating mechanism: type I hypersensitivity (IgE-mediated, directed against auto-allergens) and type IIb (autoimmune, via IgG autoantibodies directed against IgE or the IgE-receptor). Their treatment responses vary. We discuss in vitro and in vivo biomarkers.
RECENT FINDINGS
Patients with auto-allergic CSU have clinical characteristics that can distinguish them partly from those with autoimmune CSU. Most importantly, their disease generally presents a less aggressive course, a better response to second generation (up-dosed) antihistamines and a good response to omalizumab, if necessary. Meanwhile, autoimmune CSU/CindU patients fare less well and often need immunosuppressive drugs. Biomarkers that might help endotype CSU/CindU patients and select the most appropriate treatment, dose, and duration, e.g., for autoallergic CSU, high total IgE and IgE against auto-allergens; for autoimmune CSU, low IgE, basopenia, and IgG against autoantigens like thyroid peroxidase and a positive autologous serum skin test (but sometimes also positive in autoallergy). Some biomarkers are easily accessible but of low specificity; others are highly specific but more futuristic.
Topics: Humans; Urticaria; Immunoglobulin E; Chronic Urticaria; Biomarkers; Omalizumab; Allergens; Chronic Inducible Urticaria; Immunoglobulin G; Chronic Disease
PubMed: 38064133
DOI: 10.1007/s11882-023-01117-7 -
Expert Opinion on Investigational Drugs Mar 2022Across the globe, chronic urticaria (CU), i.e. chronic spontaneous urticaria (CSU) and chronic inducible urticaria (CINDU), is common, long-persisting and difficult to... (Review)
Review
INTRODUCTION
Across the globe, chronic urticaria (CU), i.e. chronic spontaneous urticaria (CSU) and chronic inducible urticaria (CINDU), is common, long-persisting and difficult to manage. Still, at least one-fifth is not sufficiently controlled by guideline-recommended treatment with H1-antihistamines and add-on therapy with the anti-IgE monoclonal antibody omalizumab.
AREAS COVERED
Using PubMed, ClinicalTrials.gov, Congress websites, and websites of the manufacturers, this review explored the pipeline, namely anti-IgE-, anti-cytokine-, anti-receptor biologics, and small molecules, in clinical development for CU.
EXPERT OPINION
The CU pipeline is promising. While three omalizumab biosimilars are investigated, the assumed early approval of ligelizumab will expand the effective and safe anti-IgE approach observed with omalizumab. For other anti-IgEs like UB-221, the development is behind. Data are too limited so far to clearly define the role of anti-cytokine and anti-cytokine receptor biologics such as dupilumab, tezepelumab, mepolizumab, benralizumab, and CDX-0159, of which only dupilumab is actually investigated in phase 3. Among three selective oral BTK inhibitors, remibrutinib, rilzabrutinib, and fenebrutinib, the development of remibrutinib is most advanced (phase 3). As the pipeline addresses different targets, study results will give deeper insights into the pathomechanisms of CU. Hopefully, in the next future additional approved and also more targeted approaches will be available.
Topics: Anti-Allergic Agents; Biosimilar Pharmaceuticals; Chronic Disease; Chronic Urticaria; Humans; Omalizumab; Urticaria
PubMed: 35166638
DOI: 10.1080/13543784.2022.2042513 -
Current Opinion in Allergy and Clinical... Jun 2023A better understanding of the most recent scientific literature in the use of biological therapy in the treatment of patients with IgE-mediated food allergy. (Meta-Analysis)
Meta-Analysis
PURPOSE OF REVIEW
A better understanding of the most recent scientific literature in the use of biological therapy in the treatment of patients with IgE-mediated food allergy.
RECENT FINDINGS
A systematic review and meta-analysis demonstrated safety and effectiveness of omalizumab in the treatment of food allergy. The findings support the potential use of omalizumab as a monotherapy or as an adjunct to oral immunotherapy in IgE-mediated cow's milk allergy. The potential use of other biologics in the management of food allergy is subject of speculation.
SUMMARY
Different biological therapies are under evaluation for food allergic patients. The advance in literature will guide for a personalized treatment in the near future. However, additional research is needed to better understand the best candidate for each treatment, the optimal dose and timing.
Topics: Animals; Female; Cattle; Humans; Omalizumab; Biological Products; Immunoglobulin E; Food Hypersensitivity; Milk Hypersensitivity; Desensitization, Immunologic
PubMed: 37185824
DOI: 10.1097/ACI.0000000000000900 -
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 -
Frontiers in Immunology 2023Bullous pemphigoid (BP) is the most common autoimmune subepidermal bullous disease. Topical or systemic corticosteroids are often used as the first-line treatment....
BACKGROUND
Bullous pemphigoid (BP) is the most common autoimmune subepidermal bullous disease. Topical or systemic corticosteroids are often used as the first-line treatment. However, long-term corticosteroid use may lead to significant side effects. Therefore, various adjuvant immunosuppressant therapies are used as steroid-sparing agents, with accumulating reports of biological treatments for severely recalcitrant BP.
OBJECTIVE
To describe the clinical and immunological features of a series of patients with recalcitrant BP treated with immunobiological therapies. To assess the efficacy and safety of their therapies.
METHODS
Patients receiving biological treatment for BP from two centers were assessed. Here, we described the clinical, immunopathological, and immunofluorescence findings of adult patients with BP and analyzed the clinical response and adverse events associated with various biological therapies.
RESULTS
We identified nine eligible patients treated with rituximab (seven), omalizumab (three), or dupilumab (one). The mean age at diagnosis was 60.4 years, the average BP duration before biologic initiation was 1.9 years, and the average previous treatment failure was 2.11 therapies. The mean follow-up period from the first biological treatment to the last visit was 29.3 months. Satisfactory response, defined as clinical improvement, was achieved in 78% (7) of the patients, and total BP clearance was achieved in 55% (5) of the patients at the last follow-up visit. Additional rituximab courses improved the disease outcomes. No adverse events were reported.
CONCLUSIONS
Efficient and safe novel therapies can be considered in recalcitrant steroid-dependent BP non-responsive to conventional immunosuppressant therapies.
Topics: Adult; Humans; Pemphigoid, Bullous; Rituximab; Immunosuppressive Agents; Omalizumab; Skin Diseases, Vesiculobullous
PubMed: 37180101
DOI: 10.3389/fimmu.2023.1157250 -
Journal of Medical Economics 2022To compare the efficacy of tezepelumab with other approved biologics indirect treatment comparisons (ITCs) in patients aged ≥ 12 years with severe uncontrolled asthma. (Meta-Analysis)
Meta-Analysis
AIMS
To compare the efficacy of tezepelumab with other approved biologics indirect treatment comparisons (ITCs) in patients aged ≥ 12 years with severe uncontrolled asthma.
MATERIALS AND METHODS
Data from randomized controlled trials (RCTs) identified from a systematic literature review were synthesized using two different ITC approaches: network meta-analysis (NMA) and simulated treatment comparison (STC). Outcomes of interest were annualized asthma exacerbation rate (AAER) and AAER for exacerbations leading to hospitalization. To address potential heterogeneity between study populations, various subgroup analyses were performed for the NMA (based on blood eosinophil count, fractional exhaled nitric oxide level, and presence of allergic asthma), and for the STC, models were adjusted for potential treatment effect modifiers. Sensitivity analyses were performed to assess the impact of study design (exclusion of non-placebo-controlled studies and non-phase 3 or 4 studies). Results were reported as rate ratios (RRs) with 95% credible/confidence intervals and ranking statistics were computed for the NMAs.
RESULTS
Sixteen RCTs were included in at least one of the ITCs. All biologics (tezepelumab, dupilumab, benralizumab, mepolizumab, reslizumab, and omalizumab) had similar efficacy, with no statistically significant RRs for either exacerbation outcome; however, tezepelumab was favorably associated with numerically lower AAERs and was ranked first in the network for both types of exacerbation outcome. This trend was consistent in the subgroup and sensitivity analyses. As with the primary NMA, the STC results did not demonstrate any significant differences between biologics, but point estimates were favorable towards tezepelumab.
LIMITATIONS
Heterogeneity between trials was observed among eligibility criteria and clinically important patient characteristics; however, the impact on findings is expected to be low, based on consistency across analyses.
CONCLUSIONS
Findings from both ITCs (NMA and STC) support the use of tezepelumab in a broad patient population of severe uncontrolled asthma of any phenotype.
Topics: Anti-Asthmatic Agents; Antibodies, Monoclonal, Humanized; Asthma; Biological Products; Eosinophils; Humans; Omalizumab
PubMed: 35570578
DOI: 10.1080/13696998.2022.2074195 -
The British Journal of Dermatology Jan 2024
Topics: Humans; Omalizumab; Pemphigoid, Bullous; Retrospective Studies; Anti-Allergic Agents; Immunoglobulin E
PubMed: 37939788
DOI: 10.1093/bjd/ljad432 -
Actas Dermo-sifiliograficas 2023
Topics: Humans; Omalizumab; Antibodies, Monoclonal, Humanized; Fatty Liver; Treatment Outcome; Anti-Asthmatic Agents
PubMed: 37301476
DOI: 10.1016/j.ad.2021.10.029 -
Actas Dermo-sifiliograficas 2023
Topics: Humans; Omalizumab; Antibodies, Monoclonal, Humanized; Fatty Liver; Treatment Outcome; Anti-Asthmatic Agents
PubMed: 36243139
DOI: 10.1016/j.ad.2021.10.023 -
Current Opinion in Allergy and Clinical... Jun 2024The aim is to update the information currently available for the use of biologics in severe asthma in children, in order to facilitate their prescription as far as... (Review)
Review
PURPOSE OF REVIEW
The aim is to update the information currently available for the use of biologics in severe asthma in children, in order to facilitate their prescription as far as possible.
RECENT FINDINGS
The appearance of biologics for the treatment of severe asthma has meant a revolutionary change in the therapeutic approach to this disease. Currently, five biologics have been approved for severe asthma in children and/or adolescents by the regulatory agencies: omalizumab, mepolizumab, benralizumab, dupilumab and tezepelumab. But despite their positive results in terms of efficacy, there are still relevant points of debate that should induce caution when selecting the most appropriate biologic in a child with severe asthma. Indeed, safety is essential and, for several of the existing treatments, the availability of medium-term to long-term data in this regard is scarce.
SUMMARY
The use of biologics can facilitate the therapeutic paradigm shift from pleiotropic treatments to personalized medicine. However, the choice of the most appropriate biologics remains a pending issue. On the other hand, to the extent that several of the biologics have been available for a relatively short time, the most robust evidence in terms of efficacy and safety in children is that of omalizumab.
Topics: Humans; Asthma; Child; Anti-Asthmatic Agents; Biological Products; Adolescent; Omalizumab; Antibodies, Monoclonal, Humanized; Precision Medicine
PubMed: 38567842
DOI: 10.1097/ACI.0000000000000987