Biologics in severe asthma: the overlap endotype - opportunities and challenges

Rovina

2021

IJMS

Severe asthma greatly affects patients’ quality of life. Major advances have occurred in the management of severe eosinophilic asthma the past few years due to the new targeted biological therapies. There are three anti-IL-5 mAbs, mepolizumab, reslizumab and benralizumab. Despite the different mechanism of blocking IL-5 the clinical effects are quite similar as randomized controlled trials and real-life studies have shown. Moreover, there are reports of responding to one after failing to respond to another anti-IL-5 therapy. Accordingly, it is challenging to explore the possible differences in the response to anti-IL-5 treatments. This might help us not only understand possible mechanisms that contribute to the resistance to treatment in this particular asthma endotype, but also to phenotype within severe eosinophilic asthma in order to treat our patients more efficiently.

Section: Randomized Control Trials Targeting Il-5 and Il-5rmentioning

confidence: 99%

Section: Differential Response To Anti-il5s: Observations and Possible Explanationsmentioning

confidence: 99%

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Treatment Challenges in Severe Eosinophilic Asthma: Differential Response to Anti-IL-5 and Anti-IL-5R Therapy

Rovina

2021

IJMS

Clin Experimental Allergy

“…[14][15][16] The identification of molecular targets and a more precise understanding of patient characteristics that would benefit the most from a specific biologic would be helpful. 17 The choice of the most appropriate biologic therapy is even more difficult in the clinical scenario of a patient in whom clinical characteristics overlap between different endotypes, allowing the selection of more than one biologic agent. Thus, a physician's first therapeutic decision, no matter how carefully has been made, may often result in suboptimal clinical response and drug discontinuation.…”

Section: The D Iffi Cult Y Of Choos Ing the B E S T B I Olog I C Trmentioning

confidence: 99%

“…As no head‐to‐head comparisons between these biologics have been attempted, assertions of superiority of one biologic agent over the other made by indirect treatment comparisons using meta‐regression and matching‐adjusted analysis may be invalid or deceptive 14‐16 . The identification of molecular targets and a more precise understanding of patient characteristics that would benefit the most from a specific biologic would be helpful 17 …”

Section: The Difficulty Of Choosing the Best Biologic Treatment For Amentioning

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

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

The Journal of Allergy and Clinical Immunology: In Practice

Effective Management of Severe Asthma with Biologic Medications in Adult Patients: A Literature Review and International Expert Opinion

Buhl¹,

Bel

Bourdin

et al. 2022

Severe asthma often remains uncontrolled despite effective treatments and evidence-based guidelines. A group of global experts in asthma and biologic medications from 9 countries considered the most relevant clinical variables to manage severe asthma in adult patients and guide treatment choice. The resulting recommendations address the investigation of biomarker levels (blood eosinophil count along with fractional concentration of exhaled nitric oxide [FeNO]), clinical features (oral corticosteroid [OCS] dependence, specific comorbid disease entities associated with severe type 2 asthma), and safety considerations. Current evidence suggests that biomarkers, including both blood or sputum eosinophil counts as well as FeNO, add prognostic and predictive value and should be measured in all patients with severe asthma. OCS use is an