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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
Reslizumab is also a humanized anti-IL-5 monoclonal antibody approved by the FDA as add-on therapy for patients 18 years or older with severe eosinophilic asthma. It is administered intravenously (IV) at 3 mg/kg over 20–50 minutes every 4 weeks [24]. Castro and colleagues reported a decrease in asthma exacerbations and significant improvement in FEV1 in subjects with peripheral eosinophil count 400 cell/μL or greater [17]. Reslizumab seems to elicit the greatest improvement in FEV1 when compared to other IL-5 blocking agents that may be, in part, related to weight dosing.
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
Reslizumab is also an anti-IL-5 IgG4 rat anti-human monoclonal antibody that binds with high affinity to the alpha subunit of IL-5, thus halting its interaction with eosinophils. It was approved by the FDA in March 2016 for patients above 18 years of age. The real difference of reslizumab is that its dosing regime is weight adjusted unlike mepolizumab, and that it is injected intravenously every 4 weeks [20]. Two duplicate phase III studies were conducted, which randomized 953 patients in total to receive either reslizumab IV or placebo. All of the patients included had severe asthma with at least one exacerbation recorded in the previous year that required OCS and blood eosinophil levels >400 cells/mL. The frequency of exacerbations was reduced almost to half in the group receiving reslizumab at the end of the 52-week treatment period [21].
A drug safety review of treating eosinophilic asthma with monoclonal antibodies
Published in Expert Opinion on Drug Safety, 2019
Patrick Mitchell, Richard Leigh
Reslizumab is an interleukin-5 (IL-5) antagonist (IgG4, kappa) that binds to IL-5 (with a dissociation constant of 81 pM), preventing IL-5 from binding to the alpha chain of the IL-5 receptor complex expressed on the eosinophil cell surface, thereby reducing the production and survival of eosinophils. Reslizumab, as an add-on therapy, is recommended in the UK as an option for the treatment of severe eosinophilic asthma that is inadequately controlled in adults despite maintenance therapy with high-dose inhaled corticosteroids plus another controller medication, only if the blood eosinophil count has been recorded as 400 cells per microliter or more; the person has had 3 or more severe asthma exacerbations needing systemic corticosteroids in the past 12 months [68]. Criteria differs slightly from country to country where it has been approved.
Primary care of asthma: new options for severe eosinophilic asthma
Published in Current Medical Research and Opinion, 2019
Neil S. Skolnik, Sean P. Carnahan
Reslizumab85 is indicated for add-on maintenance treatment of patients with severe asthma ≥18 years of age and with an eosinophilic phenotype. The safety and efficacy of reslizumab was investigated in two identical phase 3 randomized, double-blind, placebo-controlled trials that enrolled patients with evidence of eosinophilic inflammation and a history of exacerbations requiring treatment with an OCS burst while taking medium-dose ICS with or without an additional controller69. Another phase 3 trial enrolled patients with eosinophilic asthma taking medium-dose ICS with or without an additional controller70, and a different phase 3 trial enrolled patients taking medium-dose ICS with or without an additional controller regardless of eosinophil count86.