China
Africa
Explore chapters and articles related to this topic
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).
Bronchus-associated lymphoid tissue and immune-mediated respiratory diseases
Published in Phillip D. Smith, Richard S. Blumberg, Thomas T. MacDonald, Principles of Mucosal Immunology, 2020
Dale T. Umetsu, Bart Lambrecht
Humanized anti-IL-5 mAbs were approved by the FDA for the treatment of severe asthma (mepolizumab, GSK, in 2015 for patients aged 12 years or older, and reslizumab, Teva, in 2016 for adults with severe asthma). An anti-IL-5 receptor (CD125) mAb (benralizumab, AstraZeneca) was approved for severe eosinophilic asthma. These antibodies significantly reduce the number of eosinophils in the periphery and in the lung, and target patients with an eosinophilic asthma phenotype, which can be identified by elevated levels of eosinophils in peripheral blood.
Biologics in allergic disease
Published in Richard F. Lockey, Dennis K. Ledford, Allergens and Allergen Immunotherapy, 2020
Tara V. Saco, Farnaz Tabatabaian
Eosinophils are an integral part of Th2 asthma. Elevated sputum and peripheral eosinophils correlate with increased asthma exacerbations and poorly controlled asthma [1,14,15]. IL-5 is necessary for eosinophil growth, differentiation, and migration into the airways [1,16]. Mepolizumab, reslizumab, and benralizumab are three monoclonal antibodies that target IL-5. Mepolizumab and reslizumab directly bind to the IL-5 cytokine and prevent its downstream binding to the IL-5 receptor [14,17–19]. Benralizumab binds to the alpha (α) chain of IL-5 receptor, thus enhancing the antibody-dependent cell-mediated cytotoxicity causing apoptosis of eosinophils, basophils, and eosinophil progenitor cells [20]. Mepolizumab is the first IL-5 inhibitor approved by the FDA as an add-on therapy for severe persistent asthma in the 12 years and older age group. It is administered as a 100 mg subcutaneous injection every 4 weeks [21]. Mepolizumab shows improvement in the quality-of-life scores with decreased emergency room (ER) visits and hospitalizations, a 53% decrease in asthma exacerbation, an improvement of 100 mL in FEV1, and 50% reduced oral glucocorticoid use in phase 3 studies [22,23]. Subjects with higher levels of peripheral eosinophilia experience greatest benefit. Mepolizumab, 300 mg sub-Q, is FDA approved for eosinophilic granulomatosis with polyangiitis [22].
Current and emerging pharmacotherapy for pediatric allergic rhinitis
Published in Expert Opinion on Pharmacotherapy, 2021
Peter Valentin Tomazic, Doris Lang-Loidolt
Currently, biologicals/biologics, human monoclonal antibodies, targeting IgE, Interleukin 5 and Interleukin 4 and 13 are largely used or in Phase III trials. Omalizumab targeting IgE has been developed and used longest [81]. Mepolizumab and Reslizumab target IL-5 directly whereas Benralizumab targets the IL-5 receptor. Dupilumab is the most recent targeting IL-4 and 13 and thus, eosinophils and IgE antibody production. Up-stream mechanisms influencing the epithelial cytokine production are targeted by monoclonal antibodies against TSLP (Tezepelumab) and IL-33 as well as IL-25 are currently under development or tested [75]. Omalizumab and Dupilumab are currently studies for AR where the latter is not approved in all countries yet. Both show positive effects in children. Omalizumab shows a good correlation in response according to levels of IgE [82]. Dupilumab shows excellent results in comorbid asthma (reduction of severe asthma exacerbation rates, FEV1, improvement in 5-item Asthma Control Questionnaire, improved rhinoconjunctivitis-specific health-related quality of life, and type 2 inflammatory biomarkers) [83]. To date, the biggest issues are costs and adherence/effect of standard treatment. Okayama et al. showed that an improved cost/benefit ratio is reached with omalizumab if eight or more hospitalizations would be needed without the biologic treatment [82]. Apart from ethical considerations, this will be largely determined by health care systems of respecitve countries and development of costs for long-term biologic treatment in the future.
Effect of benralizumab on asthma exacerbation rates in patients with severe asthma: Systematic review and meta-analysis
Published in Canadian Journal of Respiratory, Critical Care, and Sleep Medicine, 2020
Masoud Mahdavian, Sarah A. Mallay, Shabnam Asghari, Nha Voduc, Jordan C. Pike
Asthma is a heterogeneous inflammatory airway disease; some patients with asthma are not adequately controlled despite taking low-dose inhaled corticosteroid and long-acting beta agonist inhaler. These patients with severe asthma require step 4 or 5 GINA guidelines medications or oral corticosteroid for ≥50% of the previous year to maintain control, or still remain inadequately controlled despite this.1 Many inflammatory pathways are involved in asthma; one such pathway involves the type 2 (Th2) immune response, which involves a number of immune cells including eosinophils, basophils and cytokines.2 Interleukin-5 (IL-5) is a key cytokine involved in eosinophil maturation, survival and apoptosis3 giving a potential target for biologic treatment of severe asthma. The IL-5 receptor (IL-5R) is expressed on eosinophils, basophils and their precursors in bone marrow,3 and IL-5 activation of these cells is dependent on expression of the IL-5R alpha chain (IL-5Rα).4 Targeting of the IL-5 receptor alpha chain (IL-5Rα) leads to decreases in eosinophil levels.5 For this reason, the IL-5Rα presents itself as a potential target for asthma management. Benralizumab, formerly MEDI-563, is an afucosylated, humanized, monoclonal antibody that targets the IL-5Rα expressed on eosinophils and basophils.5 It not only blocks the IL-5Rα but also induces anti-body-dependent cellular toxicity and directly involves Eosinophilic apoptosis that has been shown to diminish blood eosinophil levels in asthmatic patients.6–13
A drug safety review of treating eosinophilic asthma with monoclonal antibodies
Published in Expert Opinion on Drug Safety, 2019
Patrick Mitchell, Richard Leigh
Benralizumab is a targeted, humanized afucosylated, monoclonal antibody (IgG1, kappa) that binds to the alpha subunit of the human interleukin-5 receptor (IL-5Rα). The IL-5 receptor is expressed on the surface of eosinophils and basophils. The results of in vitro studies have also shown that the absence of fucose in the Fc domain of benralizumab results in much higher affinity binding for FcɣRIII receptors, which are expressed on immune effectors cells such as natural killer cells. This feature, unique to benralizumab in the anti IL-5 mAb class, induces apoptosis of eosinophils and basophils through enhanced antibody-dependent cell-mediated cytotoxicity (ADCC). Benralizumab reduces eosinophilic inflammation through both effective depletion of IL-5 binding sites and enhanced ADCC. However, the exact mechanism of benralizumab action in asthma has not been definitively established.