- Successful Treatment of Corticosteroid-Refractory Hypereosinophilia With Reslizumab. [Journal Article]
- JIJ Investig Allergol Clin Immunol 2019; 29(3):241-242
- Monoclonal antibodies for severe asthma: Pharmacokinetic profiles. [Review]
- RMRespir Med 2019; 153:3-13
- Several monoclonal antibodies (mAbs) (omalizumab, mepolizumab, reslizumab, benralizumab, and dupilumab) are currently approved for the treatment of severe asthma. They have complex pharmacokinetic pr…
Several monoclonal antibodies (mAbs) (omalizumab, mepolizumab, reslizumab, benralizumab, and dupilumab) are currently approved for the treatment of severe asthma. They have complex pharmacokinetic profiles. These profiles are unique in that they are dependent on their structure as well as can be markedly influenced by the biology of their target antigen, but their general behaviour can still be considered a class property, similar to their endogenous IgG counterpart. They cannot be administered by oral route, have a slow distribution into tissue, are metabolized to peptides and amino acids in several tissues but are protected from degradation by binding to protective receptors (the FcRn), which explains their long elimination half-lives. Their clearance is nonlinear because of the saturation of the target-mediated elimination. Also anti-drug antibody (ADA) response and off-target binding, as well as their glycosylation pattern, can influence the pharmacokinetics of mAbs.
- Reslizumab in an invasively ventilated patient with acute respiratory failure. [Journal Article]
- JAJ Allergy Clin Immunol Pract 2019 May 25
- Monoclonal antibodies in severe asthma: is it worth it? [Meta-Analysis]
- EOExpert Opin Drug Metab Toxicol 2019; 15(6):517-520
- CONCLUSIONS: Further extensive meta-analyses are needed to identify the factors influencing the efficacy profile of mAbs in severe asthma. This may also permit to identify the profile of patients that are specifically responsive to either anti-IgE, anti-IL-4Rα, anti-IL-5, or anti-IL-5Rα mAbs.
- New Targeted Therapies for Uncontrolled Asthma. [Review]
- JAJ Allergy Clin Immunol Pract 2019 May - Jun; 7(5):1394-1403
- Mechanistic studies have improved our understanding of molecular and cellular components involved in asthma and our ability to treat severe patients. An mAb directed against IgE (omalizumab) has beco…
Mechanistic studies have improved our understanding of molecular and cellular components involved in asthma and our ability to treat severe patients. An mAb directed against IgE (omalizumab) has become an established add-on therapy for patients with uncontrolled allergic asthma and mAbs specific for IL-5 (reslizumab, mepolizumab), IL-5R (benralizumab), and IL-4R (dupilumab) have been approved as add-on treatments for uncontrolled eosinophilic (type 2) asthma. While these medications have proven highly effective, some patients with severe allergic and/or eosinophilic asthma, as well as most patients with severe non-type-2 disease, have poorly controlled disease. Agents that have recently been evaluated in clinical trials include an antibody directed against thymic stromal lymphopoietin, small molecule antagonists to the chemoattractant receptor-homologous molecule expressed on TH2 cells (CRTH2) and the receptor for stem cell factor on mast cells (KIT), and a DNA enzyme directed at GATA3. Antibodies to IL-33 and its receptor, ST2, are being evaluated in ongoing clinical studies. In addition, a number of antagonists directed against other potential targets are under consideration for future trials, including IL-25, IL-6, TNF-like ligand 1A, CD6, and activated cell adhesion molecule (ALCAM). Clinical data from ongoing and future trials will be important in determining whether these new medications will offer benefits in place of or in addition to existing therapies for asthma.
- Therapeutic Antibodies for Nasal Polyposis Treatment: Where Are We Headed? [Review]
- CRClin Rev Allergy Immunol 2019 May 10
- This review article aims to outline what is known in the pathophysiology of chronic rhinosinusitis with nasal polyposis (CRSwNP) and describe the mechanism of the biologic agents being investigated f…
This review article aims to outline what is known in the pathophysiology of chronic rhinosinusitis with nasal polyposis (CRSwNP) and describe the mechanism of the biologic agents being investigated for this disease. Chronic rhinosinusitis with nasal polyposis is an inflammatory disease of the nasal and paranasal mucosa, which causes symptoms of nasal obstruction, hyposmia, and rhinorrhea. Conventional therapy for CRSwNP includes intranasal corticosteroids (INCS) and polypectomy, but INCS offer only modest benefits, and recurrence after surgery is common. Therefore, effective pharmacologic therapies for CRSwNP are being actively sought. Monoclonal antibodies have been successful in other chronic diseases involving eosinophilic inflammation, such as chronic urticaria and asthma. Thus, researchers have begun expanding their scope and investigating the efficacy of these drugs in the treatment of nasal polyposis. The monoclonal antibodies under investigation (omalizumab (anti IgE), dupilumab (anti IL-4/IL-13), and reslizumab and mepolizumab (both anti IL-5), benralizumab (anti IL-5Rα), and etokimab (anti IL-33)) target key players in the pathophysiology of nasal polyposis (NP). Dupilumab has just completed phase III trials for CRSwNP with positive results, while omalizumab, mepolizumab, and benralizumab are currently in phase III trials for this indication. At this time, while there are no FDA-approved biologics for use in NP, research has highlighted the contributions of IL-4, IL-5, IL-13, and IgE as disease mediators in the pathogenesis of NP. The current FDA-approved treatment of intranasal steroids does not provide significant relief for many patients; therefore, these phase III trials of monoclonal antibodies bring hope for an exciting new treatment option.
- Comparison of Monoclonal Antibodies for Treatment of Uncontrolled Eosinophilic Asthma. [Journal Article]
- JPJ Pharm Pract 2019 May 02; :897190019840597
- CONCLUSIONS: Five monoclonal antibodies are available for uncontrolled eosinophilic asthma. Choice depends on patient factors. Future studies should focus on cost-effectiveness of treatment, drug-drug comparisons, and long-term efficacy and safety.
- Efficacy and steroid-sparing effect of benralizumab: has it an advantage over its competitors? [Review]
- DCDrugs Context 2019; 8:212580
- Severe refractory asthma is characterized by a higher risk of asthma-related symptoms, morbidities, and exacerbations. This disease also determines much greater healthcare costs and deterioration in …
Severe refractory asthma is characterized by a higher risk of asthma-related symptoms, morbidities, and exacerbations. This disease also determines much greater healthcare costs and deterioration in health-related quality of life (HR-QoL). Another concern, which is currently much discussed, is the high percentage of patients needing regular use of oral corticosteroids (OCS), which can lead to several systemic side effects. Airway eosinophilia is present in the majority of asthmatic patients, and elevated levels of blood and sputum eosinophils are associated with worse control of asthma. Regarding severe refractory eosinophilic asthma, interleukin-5 (IL-5) plays a fundamental role in the inflammatory response, due to the profound effect on eosinophils biology. The advent of the biological therapies provided an effective strategy, even if the increased number of molecules with different targets raised the challenge of choosing the right therapy and avoid overlapping. When considering severe refractory eosinophilic asthma and anti-IL-5 treatments, it is not easy to define which drug to choose between mepolizumab, reslizumab, and benralizumab. In this article, we carried out an indirect comparison among literature data, especially between OCS reduction studies (ZONDA-SIRIUS) and pivotal studies (SIROCCO-MENSA), evaluating whether the clinical efficacy and the steroid-sparing effect of benralizumab may represent an advantage over other compounds. This data could help the clinician in the decision process of treatment choice, within the different available therapeutic options for eosinophilic refractory severe asthma.
- Benralizumab: A New Approach for the Treatment of Severe Eosinophilic Asthma. [Review]
- JIJ Investig Allergol Clin Immunol 2019; 29(2):84-93
- Eosinophilic asthma is the most common phenotype of severe asthma. It is characterized by abnormal production and release of type 2 cytokines from T helper type 2 (TH2) lymphocytes and type 2 innate …
Eosinophilic asthma is the most common phenotype of severe asthma. It is characterized by abnormal production and release of type 2 cytokines from T helper type 2 (TH2) lymphocytes and type 2 innate lymphoid cells, such as IL-5. This leads to a persistent increase and activation of eosinophils in blood and the airways despite treatment with high-dose inhaled corticosteroids. Eosinophil differentiation, survival, and activation are preferentially regulated by IL-5, a cytokine that binds to the IL-5 receptor (IL-5R), which is located on the surface of eosinophils or basophils and plays a critical role in the pathogenesis and severity of asthma. Benralizumab is a monoclonal antibody that binds to IL-5R via its Fab domain, blocking the binding of IL-5 to its receptor and resulting in inhibition of eosinophil differentiation and maturation in bone marrow. In addition, this antibody is able to bind through its afucosylated Fc domain to the RIIIa region of the Fcy receptor on NK cells, macrophages, and neutrophils, thus strongly inducing antibody-dependent, cell-mediated cytotoxicity in both circulating and tissue-resident eosinophils. This double function of benralizumab induces almost complete fast and maintained depletion of eosinophils that is much greater than that induced by other monoclonal antibodies targeting the IL-5 pathway, such as mepolizumab and reslizumab. This review focuses on benralizumab as an alternative to other agents targeting the IL-5 pathway in the treatment of eosinophilic asthma.
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- Correction to: Eosinophilic esophagitis. [Published Erratum]
- AAAllergy Asthma Clin Immunol 2019; 15:22
- [This corrects the article DOI: 10.1186/s13223-018-0287-0.].
[This corrects the article DOI: 10.1186/s13223-018-0287-0.].