Combination biologic therapy for severe persistent asthma

Ortega, Gilbert; Tongchinsub, Pamela; Carr, Tara F.

doi:10.1016/j.anai.2019.06.013

Cited by 37 publications

(28 citation statements)

References 10 publications

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“…Moreover, in patients with severe asthma that is uncontrolled despite receiving add-on therapy with a biologic agent, the use of combination biological therapy could be considered. However, the efficacy and safety profile of such a combination therapy in patients eligible for multiple mAbs has not been carefully studied; relevant data originate mainly from case reports [79].…”

Section: Tablementioning

confidence: 99%

Severe Asthma and Biological Therapy: When, Which, and for Whom

et al. 2019

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Asthma is a heterogeneous chronic inflammatory disease of the airways that affects approximately 300 million people worldwide. About 5-10% of all asthmatics suffer from severe or uncontrolled asthma, associated with increased mortality and hospitalization, reduced quality of life, and increased health care costs. In recent years, new treatments have become available, and different asthma phenotypes characterized by specific biomarkers have been identified. Biological drugs are currently indicated for patients with severe asthma that is not controlled with recommended treatments. They are mostly directed against inflammatory molecules of the type 2 inflammatory pathway and are effective at reducing exacerbations, maintaining control over asthma symptoms, and reducing systemic steroid use, which is associated with well-known adverse events. Although biological drugs for severe asthma have had a major impact on the management of the disease, there is still a need for head-to-head comparison studies of biologics and to identify new biomarkers for asthma diagnosis, prognosis, and response to treatment. Identifying novel biomarkers could facilitate the development of therapeutic strategies that are precisely tailored to each patient's requirements.

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Section: Tablementioning

confidence: 99%

Severe Asthma and Biological Therapy: When, Which, and for Whom

et al. 2019

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“…Interestingly, clinical improvement together with improved control of comorbid conditions (i.e. urticaria) was achieved with the combination of different biologics 58 . Although these reported cases did not reveal any adverse events on patients receiving two different classes of biologics, it cannot be ensured that the co‐administration of two monoclonal antibodies would not result in increased risk of adverse events.…”

Section: Combining Different Biologics: the ‘Mix And Match’ Approachmentioning

confidence: 90%

“…Apart from the concerns of this ‘mix and match’ approach regarding the increased cost of therapy, it is also unclear whether safety issues could occur. Recently, Ortega et al 58 have reported 3 different cases of patients with refractory disease in whom clinical improvement was achieved using multiple combinations of different biologic agents. These patients received a combination of omalizumab with either mepolizumab, benralizumab or dupilumab, in different schemes and for different period of times.…”

Section: Combining Different Biologics: the ‘Mix And Match’ Approachmentioning

confidence: 99%

Switching between biologics in severe asthma patients. When the first choice is not proven to be the best

Papaioannou

Fouka

Papakosta

et al. 2020

Clin Experimental Allergy

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During the last decades, new treatments targeting disease mechanisms referred as biologics have been introduced in the therapy of asthma, resulting in a revolution in disease control and medical history. These treatments include monoclonal antibodies, recombinant cytokines and fusion proteins, with the former to be, at the moment, the only approved biological therapy for severe refractory asthma, also included in the disease recommendations. 1 To date, five monoclonal antibodies have been approved for the treatment of asthma. Omalizumab, the first biologic drug approved for the treatment of severe allergic asthma, is a recombinant humanized monoclonal antibody that selectively targets circulating IgE and blocks it from binding to its receptor found on mast cells and basophils. Omalizumab interrupts the IgE mediated asthma inflammatory cascade at an early stage 2 and thus, interrupts both early and late asthmatic responses. 3,4 Mepolizumab and reslizumab both target IL-5, which is a key component in eosinophil proliferation, activation and recruitment, preventing consequently its binding to the α-chain of the IL-5 receptor (IL-5α) on eosinophils. 5,6 Benralizumab targets directly IL-5Rα in all cells that express the receptor, such as eosinophils, basophils and mast cells, resulting not only in the blockade of IL-5 mediated survival of these cells but also in a direct eosinophil apoptosis augmentation, via antibody-dependant cell-mediated cytotoxity (ADCC) induced by the enhanced activation of the FcγRIIIa part of the IL-5Rα receptor of mature natural-killer (NK) cells and macrophages, leading in a near depletion of peripheral eosinophils. 7,8 All three

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“…Until now, limited data exist for the use of combination biologics upon the treatment of severe persistent asthma. Case reports have been published referring to the combination of biologic therapies with controversial results [ 122 , 123 ]. The eligible patients were subjects that, despite clinical improvement on one biologic agent during the first 6 months of treatment, still did not meet the goals of therapy and have too high of a risk to discontinue the initial agent before achieving steady-state concentrations of an alternate drug [ 123 ].…”

Section: Future Perspectives On Treatmentmentioning

confidence: 99%

Eosinophilic Asthma, Phenotypes-Endotypes and Current Biomarkers of Choice

Porpodis

Tsiouprou

Apostolopoulos

et al. 2022

JPM

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Asthma phenotyping and endotyping are constantly evolving. Currently, several biologic agents have been developed towards a personalized approach to asthma management. This review will focus on different eosinophilic phenotypes and Th2-associated endotypes with eosinophilic inflammation. Additionally, airway remodeling is analyzed as a key feature of asthmatic eosinophilic endotypes. In addition, evidence of biomarkers is examined with a predictive value to identify patients with severe, uncontrolled asthma who may benefit from new treatment options. Finally, there will be a discussion on the results from clinical trials regarding severe eosinophilic asthma and how the inhibition of the eosinophilic pathway by targeted treatments has led to the reduction of recurrent exacerbations.

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Combination biologic therapy for severe persistent asthma

Cited by 37 publications

References 10 publications

Severe Asthma and Biological Therapy: When, Which, and for Whom

Severe Asthma and Biological Therapy: When, Which, and for Whom

Switching between biologics in severe asthma patients. When the first choice is not proven to be the best

Eosinophilic Asthma, Phenotypes-Endotypes and Current Biomarkers of Choice

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