Principles of Treatment for Arthropod Bites, Stings, and Other Exposure
Gail Miriam Moraru, Jerome Goddard in The Goddard Guide to Arthropods of Medical Importance, Seventh Edition, 2019
In certain arthropod-related allergies (including asthma), such as dust mite or cockroach allergies, inhaled steroids, leukotriene antagonists, or cromolyn sodium may sometimes be used. For severe asthma, research has shown that anti-IgE products such as omalizumab can significantly reduce the number of days with asthma and allow reduction of inhaled steroid use.8,9 Other monoclonal antibodies such as benralizumab which targets an interleukin-5 receptor have shown benefit for persons with severe asthma.10 Cromolyn stabilizes mast cells against degranulation, thus preventing release of histamine, leukotrienes, and other pharmacological mediators. The use of epinephrine in severe or systemic hypersensitivity reactions acts to suppress (stabilize) mediator release from mast cells and basophils and reverses many of the end-organ responses to the pharmacological mediators of anaphylaxis, resulting in bronchodilation and relaxation of smooth muscle. The prompt use of epinephrine can often lead to complete resolution of the clinical manifestations of anaphylaxis within minutes.11
The Pharmacotherapy of Rhinitis and Asthma
Pudupakkam K Vedanthan, Harold S Nelson, Shripad N Agashe, PA Mahesh, Rohit Katial in Textbook of Allergy for the Clinician, 2021
Since 2015, there have been three anti-IL-5 therapies (mepolizumab, reslizumab and benralizumab) approved for add-on maintenance treatment for patients with severe eosinophilic asthma. Mepolizumab is a recombinant, humanized IgG1κ monoclonal antibody against IL-5 that inhibits IL-5 from binding to the α-subunit of the IL-5 receptor complex expressed on the eosinophil cell surface. There is a small risk for hypersensitivity reactions and herpes zoster infections with mepolizumab. Reslizumab is a humanized IgG4κ monoclonal anti-IL-5 antibody that also inhibits binding of IL-5 to its receptor. As opposed to mepolizumab that is given subcutaneously, reslizumab is given intravenously. There are small risks for developing anaphylaxis and elevated creatinine phosphokinase levels with reslizumab. Both mepolizumab and reslizumab inhibit the growth, differentiation, recruitment, activation and survival of eosinophils. Benralizumab is a humanized afucosylated recombinant IgG1κ monoclonal antibody that binds with high affinity to the α-subunit of the IL-5 receptor. By doing so, benralizumab inhibits the proliferation and activation of eosinophils by blocking the same IL-5-mediated eosinophil properties that are blocked by mepolizumab and reslizumab. In addition, the Fc portion of benralizumab binds to Fc receptors on immune effector cells, such as natural killer cells, which then deplete existing eosinophils and precursors in the bone marrow by inducing apoptosis through antibody-dependent cell-mediated cytotoxicity (Assaf and Hanania 2019, Katial et al. 2017).
Examples from Actual Clinical Trials in Choosing and Specifying Estimands
Craig Mallinckrodt, Geert Molenberghs, Ilya Lipkovich, Bohdana Ratitch in Estimands, Estimators and Sensitivity Analysis in Clinical Trials, 2019
The SIROCCO trial was a randomized, placebo-controlled Phase 3 study of patients with severe asthma uncontrolled with high-dosage ICSs and LABAs. Patients were randomly assigned to one of the three treatment groups: subcutaneous benralizumab 30 mg either every 4 weeks (Q4W) or every 8 weeks (Q8W), or matching placebo. Patients received study drug injections at clinical centers every 4 weeks for the duration of 48 weeks. Planned assessment times included the randomization visit (Week 0) and visits at 4-week intervals during the treatment period (Weeks 4, 8, 12, …, 48). The primary endpoint was the number of asthma exacerbations evaluated over 48 weeks. A key secondary endpoint was the change from baseline to Week 48 in the prebronchodilator FEV1. The study sample was drawn from an enriched population of patients with blood eosinophil counts of at least 300 cells per microliter at baseline. The objective was to assess the effect of benralizumab as an add-on treatment; therefore, patients continued taking their background asthma controller treatments with a stable prestudy dosage and regimen during the study treatment period. The allowed rescue therapy, discouraged/disallowed medications, and management of exacerbation events were similar to the typical setting of an add-on treatment trial for severe asthma patients described above.
Hypereosinophilic syndromes in the precision medicine era: clinical, molecular aspects and therapeutic approaches (targeted therapies)
Published in Expert Review of Hematology, 2019
Alessandra Iurlo, Daniele Cattaneo, Umberto Gianelli
Benralizumab is a humanized anti-IL-5Rα monoclonal antibody which was approved by FDA in November 2017 for the treatment of severe asthma in patients age 12 and over. Upon binding to IL-5R, eosinophils become a target for destruction by NK cells via antibody-dependent cell-mediated cytotoxicity [99]. In the phase 3 SIROCCO trial, in the benralizumab group subjects with severe eosinophilic asthma had drastically reduced AECs by week 4 of treatment, whereas in the placebo group this parameter remained unchanged. This reduction was maintained at week 48 [100]. The CALIMA trial showed similar results on PB AECs over 56 weeks of therapy [101]. Another phase 3 trial (the ZONDA trial) demonstrated comparable results in patients with severe CS-dependent asthma, with subjects in the benralizumab treatment groups showing a dramatically AECs reduction at week 12 from initiating treatment [102]. Subjects in the benralizumab arms also achieved a median reduction in their oral CS doses by 75%, compared to a 25% reduction in the placebo group [102].
Impact of benralizumab on asthma exacerbation-related medical healthcare resource utilization and medical costs: results from the ZEPHYR 2 study
Published in Journal of Medical Economics, 2023
Yen Chung, Diego J. Maselli, Fan Mu, Erin E. Cook, Danni Yang, Joshua A. Young, Keith A. Betts, Eduardo Genofre, Donna Carstens
Benralizumab is a biologic medication that targets the alpha subunit of the interleukin 5 receptor (IL-5Rα), which leads to the destruction of eosinophils and prevents production of eosinophils, and is indicated as an add-on treatment for patients aged ≥12 years with severe eosinophilic asthma13. The recommended dose of benralizumab is 30 mg once every 4 weeks for the first 3 doses followed by one every 8 weeks thereafter. Real-world studies have shown that benralizumab significantly decreases the rate of asthma exacerbations and systemic CS use and improves lung function in patients with severe eosinophilic asthma14–18. Importantly, the demonstrated clinical improvements associated with benralizumab have translated into substantial cost savings. In the ZEPHYR1 study, patients with severe eosinophilic asthma in the US who received benralizumab had fewer exacerbations and reduced oral CS dependence, accompanied by lower HRU and medical costs, compared with the 12-month period before treatment initiation16.
Targeted management of severe asthma: Developing a Canadian approach
Published in Canadian Journal of Respiratory, Critical Care, and Sleep Medicine, 2020
Kenneth R. Chapman, Erika Penz, J. Mark FitzGerald
Improved understanding of the pathophysiology of asthma in general, and severe asthma in particular, has enabled development of new therapeutic agents. Canadian clinicians and researchers have played a pivotal role in these developments. There are now several biologic therapies available for the treatment of severe asthma. Omalizumab, an anti-IgE therapy, is indicated for patients more than 6 years of age with moderate to severe persistent asthma, a positive skin test or in vitro reaction to a perennial aero-allergen, and inadequately controlled symptoms.17 Mepolizumab, reslizumab and benralizumab all disrupt interleukin (IL)-5-mediated activation of eosinophils. Mepolizumab and reslizumab interact with the IL-5 ligand directly, preventing binding with the receptor.18,19 Benralizumab binds to the IL-5Rα receptor, disrupting IL-5 interactions and recruiting immune effector cells to deplete eosinophils (as well basophils).20 For a more thorough review of postulated mechanisms and biomarkers, the reader is directed elsewhere.21,22
Related Knowledge Centers
- Asthma
- Clinical Endpoint
- Injection Site Reaction
- Monoclonal Antibody
- Orphan Drug
- Alpha Chain
- Interleukin-5 Receptor
- Interleukin 5 Receptor Alpha Subunit
- Eosinophilic Esophagitis