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Pulmonary – Treatable traits
Published in Vibeke Backer, Peter G. Gibson, Ian D. Pavord, The Asthmas, 2023
Vibeke Backer, Peter G. Gibson, Ian D. Pavord
Mepolizumab and Reslizumab bind to and inactivate IL-5 thereby reducing the peripheral blood eosinophil count to low levels (typically <100 cells/mcL). Benralizumab does this by binding to the IL-5 receptor-alpha and, as a result of augmentation of eosinophil apoptosis via antibody-dependent cell-mediated cytotoxicity, does so more completely and quickly than biological agents targeting the cytokine. Mepolizumab is administered as a subcutaneous injection every 4 weeks, Benralizumab a subcutaneous injection every 8 weeks after monthly injections for 3 months and Reslizumab via a weight-based IV injection every 4 weeks.
The Pharmacotherapy of Rhinitis and Asthma
Published in Pudupakkam K Vedanthan, Harold S Nelson, Shripad N Agashe, PA Mahesh, Rohit Katial, Textbook of Allergy for the Clinician, 2021
Amanda Grippen Goddard, Harold S. Nelson, Rohit Katial, Flavia Hoyte
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).
Biologics in allergic disease
Published in Richard F. Lockey, Dennis K. Ledford, Allergens and Allergen Immunotherapy, 2020
Tara V. Saco, Farnaz Tabatabaian
Benralizumab, a monoclonal antibody that targets the alpha (α) IL-5 receptor, was FDA approved in 2017 as add-on therapy for moderate to severe eosinophilic asthma in the 12 years or older age group. Thirty milligrams sub-Q are injected for the first three doses at 4-week intervals and subsequently, every 8 weeks [20]. Its direct effect on eosinophils is attractive as these cells can subsequently enter the tissue independent of IL-5. Benralizumab does decrease asthma exacerbations, improve the FEV1, and in asthma improve quality-of-life scores. The greatest effect occurs in subjects with eosinophil count ≥300 cells/μL [18,25–27].
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.
Chronic obstructive pulmonary disease
Published in Canadian Journal of Respiratory, Critical Care, and Sleep Medicine, 2021
Erika Penz, Michael K. Stickland, Brandie Walker
Criner et al.10 published an analysis of 2 trials that studied the use of benralizumab in COPD. The GALATHEA and TERRANOVA trials were negative,11 demonstrating no effect of benralizumab on the annualized exacerbation rate in the study population consisting of moderate to very severe COPD patients with recent history of exacerbation. This prespecified exploratory analysis of the data from the 2 studies sought to determine if there are any characteristics (such as blood eosinophil level plus post bronchodilator FEV1, post-bronchodilator response or number of prior exacerbations) that may help identify patients who benefit from these medications. In turn, this information may be used to spark future research. Covariates that were strongly influential in both studies were included in the structured analysis. In the group of patients with blood eosinophils over 220 cells per uL and who were treated with 100 ug of Benralizumab every 8 weeks the group of characteristics that most strongly predicted a response was a history of 3 or more exacerbations within the last 12 months, post bronchodilator FEV1 of <40% and a bronchodilator response of >15%. This hypothesis generating study has identified some easily identifiable traits for further research that may help open up another treatment modality for this symptomatic and at risk population.
Biologics in severe asthma: the overlap endotype - opportunities and challenges
Published in Expert Opinion on Biological Therapy, 2020
A Bakakos, S Loukides, O S Usmani, P Bakakos
Two phase III trials were published in 2016 which produced similar results, the reduction of annual exacerbation rates and improvement of asthma control and FEV1. In the SIROCO study benralizumab was administered to patients with eosinophil blood count >300/mL every four or eight weeks. The group which received treatment every four weeks showed a reduction of 45% in exacerbation rates while the group that received benralizumab every eight weeks demonstrated a 51% reduction compared to placebo, during the 48 week period of the trial. The eight week group also showed larger improvements in lung function, with an average of +159 mL FEV1 compared to placebo. These findings can pave the way for benralizumab since it can drastically reduce healthcare costs by treating patients with an eight week interval instead of monthly treatment [25]. The CALIMA study was published at the same year and had a similar design with SIROCO. The annual exacerbation rates were reduced by up to 36% in the four week group and the FEV1 improvement was almost similar (125–120 mL) in the two dosing scheme groups when compared to placebo. In both studies the patients randomized to benralizumab had no severe side effects [26].