A Possible Explanation for Non-responders, Responders and Super-responders to Biologics in Severe Asthma

Hyland, Michael E.; Masoli, Matthew; Lanario, Joseph W.; Jones, Rupert

doi:10.14218/erhm.2019.00008

Cited by 3 publications

(2 citation statements)

References 23 publications

(20 reference statements)

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“…This number is in line with the results of large randomized, controlled trials because the response rate ranged between 76% and 83% in those trials. 23 However, although biological therapies are effective, more than 50% of our patients still took OCS either daily (25.2%) or at least three times a year as short-course therapy (25.6%) in our study. In the PONENTE trial, which assessed the rate of OCS elimination after introducing benralizumab for patients receiving long-term oral steroids, 37.12% were still given oral steroids at 1 year.…”

Section: Discussionmentioning

confidence: 65%

Improvement in severe asthma patients receiving biologics and factors associated with persistent insufficient control: a real-life national study

Guilleminault,

Camus,

Raherison-Semjen

et al. 2023

Ther Adv Respir Dis

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Background: Biological therapies have revolutionized the treatment of severe asthma with type 2 inflammation. Although such treatments are very effective in reducing exacerbation and the dose of oral steroids, little is known about the persistence of symptoms in severe asthma patients treated with biologics. Purpose: We aim to describe asthma control and healthcare consumption of severe asthma patients treated with biologics. Design: The Second Souffle study is a real-life prospective observational study endorsed by the Clinical Research Initiative in Severe Asthma: a Lever for Innovation & Science Network. Methods: Adults with a confirmed diagnosis of severe asthma for at least 12 months’ duration were enrolled in the study. A self-administered questionnaire including the Asthma Control Questionnaire (ACQ), Asthma Quality of Life Questionnaire (AQLQ) and a compliance evaluation test was given to the patients. Healthcare consumption within 12 months prior to enrolment was documented. In patients receiving biologics, doctors indicated whether the patients were biologic responders or non-responders. Results: The characteristics of 431 patients with severe asthma were analysed. Among them, 409 patients (94.9%) presented asthma with type 2 inflammation (T2 high) profile, and 297 (72.6%) patients with a T2 high phenotype were treated with a biologic. Physicians estimated that 88.2% of patients receiving biologics were responders. However, asthma control was only achieved in 25.3% of those patients (ACQ > 0.75). A high proportion of patients (77.8%) identified as responders to biologics were not controlled according to the ACQ score. About 50% of patients continue to use oral corticosteroids either daily (25.2%) or more than three times a year for at least three consecutive days (25.6%). Gastro-oesophageal Reflux Disease (GERD) and Obstructive Sleep Apnoea syndrome (OSA) were identified as independent factors associated with uncontrolled asthma. Conclusion: Although a high proportion of severe asthma patients respond to biologics, only 25.3% have controlled asthma. GERD and OSA are independent factors of uncontrolled asthma.

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Section: Discussionmentioning

confidence: 65%

Improvement in severe asthma patients receiving biologics and factors associated with persistent insufficient control: a real-life national study

Guilleminault,

Camus,

Raherison-Semjen

et al. 2023

Ther Adv Respir Dis

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“…A new theoretical model for the action of biologics shows that the target molecule is part of a causal network of different inflammatory and non-inflammatory markers that influence reciprocally. 62 Therefore, many factors may contribute to mAbs response or non-response in patients with severe eosinophilic asthma, but with the studies currently available, there are still pitfalls that need further investigations to find out whether patients will receive more or less benefits from the biological therapy.…”

Section: Discussionmentioning

confidence: 99%

Treating severe asthma: Targeting the IL‐5 pathway

Principe

Porsbjerg

Ditlev

et al. 2021

Clin Experimental Allergy

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Severe asthma is a heterogeneous disease with different phenotypes based on clinical, functional or inflammatory parameters. In particular, the eosinophilic phenotype is associated with type 2 inflammation and increased levels of interleukin (IL)‐4, IL‐5 and IL‐13). Monoclonal antibodies that target the eosinophilic inflammatory pathways (IL‐5R and IL‐5), namely mepolizumab, reslizumab, and benralizumab, are effective and safe for severe eosinophilic asthma. Eosinophils threshold represents the most indicative biomarker for response to treatment with all three monoclonal antibodies. Improvement in asthma symptoms scores, lung function, the number of exacerbations, history of late‐onset asthma, chronic rhinosinusitis with nasal polyposis, low oral corticosteroids use and low body mass index represent predictive clinical markers of response. Novel Omics studies are emerging with proteomics data and exhaled breath analyses. These may prove useful as biomarkers of response and non‐response biologics. Moreover, future biomarker studies need to be undertaken in paediatric patients affected by severe asthma. The choice of appropriate biologic therapy for severe asthma remains challenging. The importance of finding biomarkers that can predict response continuous an open issue that needs to be further explored. This review describes the clinical effects of targeting the IL‐5 pathway in severe asthma in adult and paediatric patients, focusing on predictors of response and non‐response.

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Monoclonal antibodies in the management of asthma: Dead ends, current status and future perspectives

et al. 2022

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Patients with moderate-to-severe asthma may now be treated using a variety of monoclonal antibodies that target key inflammatory cytokines involved in disease pathogenesis. Existing clinical data on anti-IgE, anti-IL-5 and other immunological pathways indicate these therapies to offer reduced exacerbation rates, improved lung function, greater asthma control and better quality of life. However, as several patients still do not achieve satisfactory clinical response with the antibodies available, many more biologics, aiming different immunological pathways, are under evaluation. This review summarizes recent data on existing and potential monoclonal antibodies in asthma. Recent advances have resulted in the registration of a new antibody targeting TSLP (tezepelumab), with others being under development. Some of the researched monoclonal antibodies (e.g. anti-IL-13 tralokinumab and lebrikizumab or anti-IL-17A secukinumab) have shown optimistic results in preliminary research; however, these have been discontinued in asthma clinical research. In addition, as available monoclonal antibody treatments have shown little benefit among patients with T2-low asthma, research continues in this area, with several antibodies in development. This article summarizes the available pre-clinical and clinical data on new and emerging drugs for treating severe asthma, discusses discontinued treatments and outlines future directions in this area.

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A Possible Explanation for Non-responders, Responders and Super-responders to Biologics in Severe Asthma

Cited by 3 publications

References 23 publications

Improvement in severe asthma patients receiving biologics and factors associated with persistent insufficient control: a real-life national study

Improvement in severe asthma patients receiving biologics and factors associated with persistent insufficient control: a real-life national study

Treating severe asthma: Targeting the IL‐5 pathway

Monoclonal antibodies in the management of asthma: Dead ends, current status and future perspectives

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