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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 Journal of Allergy and Clinical... Mar 2019Cells that express FcεRI, including mast cells, basophils, and plasmacytoid dendritic cells (pDCs), are regulated by IgE binding to FcεRI. Omalizumab binds IgE and...
Cells that express FcεRI, including mast cells, basophils, and plasmacytoid dendritic cells (pDCs), are regulated by IgE binding to FcεRI. Omalizumab binds IgE and prevents its engagement with FcεRI, thereby downregulating its expression and modulating cell function. Because these cells are implicated in the pathobiology of many allergic and immunologic diseases, as well as host defense mechanisms, it is unsurprising that omalizumab studies continue yielding biologic insights and treatment break-throughs for many diseases. Several recent updates in the biology and use of omalizumab will be presented here, and others will be summarized in Table I, highlighting available biomarker-based personalized approaches.
Topics: Anti-Allergic Agents; Anti-Asthmatic Agents; Antiviral Agents; Eosinophils; Humans; Omalizumab; Urticaria; Virus Diseases
PubMed: 30690050
DOI: 10.1016/j.jaci.2019.01.016 -
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 -
Human Vaccines & Immunotherapeutics Oct 2017Oral immunotherapy (OIT) is used regularly for young children with cow's milk (CM) allergy and has been shown to be effective in several studies. However, adverse events... (Review)
Review
Oral immunotherapy (OIT) is used regularly for young children with cow's milk (CM) allergy and has been shown to be effective in several studies. However, adverse events occur frequently during OIT. Furthermore, there are only 5 randomized controlled trial studies of CM-OIT and these are low-powered single center trials. Therefore, evidence levels are also low and sometimes frequent and severe allergic events occur during the OIT. Furthermore, there are no standardized protocols in pediatric allergy guidelines from several countries and studies with long-term follow-up observations and clinical tolerance defined as sustained unresponsiveness are rare. Additionally, clinical tolerance by OIT is generally not well defined and obscure. Thus, several problems remain to be resolved, however we hope OIT in combination with omalizumab and less allergenic heated CM products will resolve these problems in the future.
Topics: Administration, Oral; Adolescent; Animals; Cattle; Child; Child, Preschool; Clinical Trials as Topic; Desensitization, Immunologic; Female; Humans; Immune Tolerance; Male; Microwaves; Milk; Milk Hypersensitivity; Omalizumab
PubMed: 28825866
DOI: 10.1080/21645515.2017.1353845 -
Journal of Immunology (Baltimore, Md. :... Dec 2016IgE is the least abundant Ig isotype, yet it plays a critical role in allergic reactions and host protection from helminth infection. Although IgE was discovered 50... (Review)
Review
IgE is the least abundant Ig isotype, yet it plays a critical role in allergic reactions and host protection from helminth infection. Although IgE was discovered 50 years ago, the ultimate evidence for its role in human allergic diseases was obtained by the efficacy of anti-IgE therapy in many clinical trials on asthma and other allergic diseases. Beginning from the discovery of IgE 50 y ago, followed by studies of IgE receptors and activation mechanisms, this review provides a historic perspective of allergy research that has led to the development of anti-IgE therapy and other strategies targeting IgE and its receptors. Current IgE studies toward future precision medicine are also reviewed.
Topics: Asthma; Clinical Trials as Topic; Humans; Immunoglobulin E; Omalizumab
PubMed: 27864548
DOI: 10.4049/jimmunol.1601476 -
Clinical Reviews in Allergy & Immunology Jun 2018Non-hereditary angioedema (AE) with normal C1 esterase inhibitor (C1INH) can be presumably bradykinin- or mast cell-mediated, or of unknown cause. In this systematic... (Review)
Review
Non-hereditary angioedema (AE) with normal C1 esterase inhibitor (C1INH) can be presumably bradykinin- or mast cell-mediated, or of unknown cause. In this systematic review, we searched PubMed, EMBASE, and Scopus to provide an overview of the efficacy of different treatment options for the abovementioned subtypes of refractory non-hereditary AE with or without wheals and with normal C1INH. After study selection and risk of bias assessment, 61 articles were included for data extraction and analysis. Therapies were described for angiotensin-converting enzyme inhibitor-induced AE (ACEi-AE), for idiopathic AE, and for AE with wheals. Described treatments consisted of ecallantide, icatibant, C1INH, fresh frozen plasma (FFP), tranexamic acid (TA), and omalizumab. Additionally, individual studies for anti-vitamin K, progestin, and methotrexate were found. Safety information was available in 26 articles. Most therapies were used off-label and in few patients. There is a need for additional studies with a high level of evidence. In conclusion, in acute attacks of ACEi-AE and idiopathic AE, treatment with icatibant, C1INH, TA, and FFP often leads to symptom relief within 2 h, with limited side effects. For prophylactic treatment of idiopathic AE and AE with wheals, omalizumab, TA, and C1INH were effective and safe in the majority of patients.
Topics: Angioedema; Angiotensin-Converting Enzyme Inhibitors; Bradykinin; Humans; Omalizumab; Progestins; Tranexamic Acid; Treatment Outcome
PubMed: 27672078
DOI: 10.1007/s12016-016-8585-0 -
Clinical and Translational Science Aug 2023Allergic conditions, such as asthma, chronic urticaria, atopic dermatitis (AD), and eosinophilic esophagitis, have long been treated with oral and topical steroids which... (Review)
Review
Allergic conditions, such as asthma, chronic urticaria, atopic dermatitis (AD), and eosinophilic esophagitis, have long been treated with oral and topical steroids which resulted in negative off-target effects. However, newer biologic medications are increasingly being developed and approved for treatment of these conditions. These medications have a variety of mechanisms of action to target pathophysiology specific to these diseases. As biologics become more targeted, fewer off-target effects are seen improving tolerability for patients as well as expanded options for treatment of these conditions. This review discusses monoclonal antibody therapies (omalizumab, mepolizumab, reslizumab, benralizumab, dupilumab, tezepelumab, and tralokinumab) including their safety and use in asthma, chronic urticaria, AD, and eosinophilic esophagitis.
Topics: Humans; Eosinophilic Esophagitis; Omalizumab; Asthma; Immunotherapy; Dermatitis, Atopic; Chronic Urticaria
PubMed: 37170653
DOI: 10.1111/cts.13546 -
Journal of Immunology Research 2016IgE is an immunoglobulin that plays a central role in acute allergic reactions and chronic inflammatory allergic diseases. The development of a drug able to neutralize... (Review)
Review
IgE is an immunoglobulin that plays a central role in acute allergic reactions and chronic inflammatory allergic diseases. The development of a drug able to neutralize this antibody represents a breakthrough in the treatment of inflammatory pathologies with a probable allergic basis. This review focuses on IgE-related chronic diseases, such as allergic asthma and chronic urticaria (CU), and on the role of the anti-IgE monoclonal antibody, omalizumab, in their treatment. We also assess the off-label use of omalizumab for other pathologies associated with IgE and report the latest findings concerning this drug and other new related drugs. To date, omalizumab has only been approved for severe allergic asthma and unresponsive chronic urticaria treatments. In allergic asthma, omalizumab has demonstrated its efficacy in reducing the dose of inhaled corticosteroids required by patients, decreasing the number of asthma exacerbations, and limiting the effect on airway remodeling. In CU, omalizumab treatment rapidly improves symptoms and in some cases achieves complete disease remission. In systemic mastocytosis, omalizumab also improves symptoms and its prophylactic use to prevent anaphylactic reactions has also been discussed. In other pathologies such as atopic dermatitis, food allergy, allergic rhinitis, nasal polyposis, and keratoconjunctivitis, omalizumab significantly improves clinical manifestations. Omalizumab acts in two ways: by sequestering free IgE and by accelerating the dissociation of the IgE-Fc receptor I complex.
Topics: Anaphylaxis; Anti-Allergic Agents; Anti-Asthmatic Agents; Antibodies, Anti-Idiotypic; Antibodies, Monoclonal; Asthma; Humans; Immunoglobulin E; Off-Label Use; Omalizumab; Receptors, IgE; Urticaria
PubMed: 28097159
DOI: 10.1155/2016/8163803