Increase in systemic IL-5 is associated with mepolizumab treatment failure in patients with severe asthma

Škrgat, Sabina; Sušanj, Petra Girandon; Stojković, Urška Bidovec; Korošec, Peter

doi:10.1183/13993003.congress-2018.pa1132

Cited by 5 publications

(9 citation statements)

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“…We found a statistically significant increase in IL-5 after the initiation of treatment compared with the baseline values in nonresponders and responders. This has also been observed in previous studies [40][41][42]. Possible causes of elevated IL-5 levels during anti-IL5 treatment are the formation of immune complexes between IL-5 and anti-IL-5 antibodies (monoclonal antibodies bind IL-5 and prevent degradation of IL-5), increased IL-5 receptor expression, and/or increased T helper cells that produce intracellular IL-5.…”

Section: Discussionsupporting

confidence: 83%

Heterogeneous Response of Airway Eosinophilia to Anti-IL-5 Biologics in Severe Asthma Patients

Šokić

Rijavec

Korošec

et al. 2022

JPM

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Many questions concerning responders (R) and nonresponders (NR) in severe eosinophilic asthma (SEA) after blocking the IL-5 (interleukin 5) pathway are still not clear, especially regarding the early parameters of response to biologics in personalized treatment strategies. We evaluated 17 SEA patients treated with anti-IL-5 biologics (16 patients mepolizumab, one patient benralizumab) before the introduction of biologics, and at a week 16 follow-up. Clinical, cellular and immunological parameters in peripheral blood were measured in R and NR. Sputum induction with the measurement of cellular and immunological parameters was performed at 16 weeks only. There were 12 R and 5 NR to biologics. After 16 weeks, there was a significant improvement in percentages of FEV1 (p = 0.001), and asthma control test (ACT) (p = 0.001) in the R group, but not in NR. After 16 weeks, the eosinophils in induced sputum were 27.0% in NR and 4.5% in R (p = 0.05), with no difference in IL-5 concentrations (p = 0.743). Peripheral eosinophilia decreased significantly in NR (p = 0.032) and R (p = 0.002). In patients with SEA on anti-IL-5 therapy, there was a marked difference in airway eosinophilic inflammation between R and NR already at 16 weeks, after anti-IL-5 introduction.

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Section: Discussionsupporting

confidence: 83%

Heterogeneous Response of Airway Eosinophilia to Anti-IL-5 Biologics in Severe Asthma Patients

Šokić

Rijavec

Korošec

et al. 2022

JPM

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“…70 The serum IL-5 detected during treatment with mepolizumab may be part of a bound immunoglobulin complex that prolongs the half-life of IL-5, leading to detection of increased levels. 71 One major limitation of this study is that the casecontrol design captured clinical and mechanistic data from only a single visit, without any longitudinal data available to gauge each patient's response to mepolizumab. Therefore, the treatment-related immunologic differences seen in this study are presumed to be directly mediated by mepolizumab, but without repeat measures, this cannot be fully confirmed.…”

Section: Discussionmentioning

confidence: 99%

Mepolizumab targets multiple immune cells in aspirin-exacerbated respiratory disease

Buchheit

Lewis

Gakpo

et al. 2021

Journal of Allergy and Clinical Immunology

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“…A small study in 5 patients found that non-responders, according to OCS-use and exacerbation frequency, had an increase in IL-5 concentrations at 12 weeks, but these results need to be confirmed in larger studies. [85] Siglec-8, a transmembrane receptor on eosinophils, may act as a surrogate parameter, since it is regulated by IL-5. In a study in 12 patients, it was found that patients with low serum Siglec-8 had a trend towards better FEV1 and AQLQ improvements, but no correlation with serum eosinophil counts was found.…”

Section: Mepolizumab: Baseline Characteristics To Predict Medium and Long Term Treatment Responsementioning

confidence: 99%

Prediction of response to biological treatment with monoclonal antibodies in severe asthma

Kroes

Zielhuis

Roon

et al. 2020

Biochemical Pharmacology

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In recent years, major developments have occurred in severe asthma management. Different asthma phenotypes and subgroups have been identified and new treatment options have become available. A total of five monoclonal antibodies are currently approved in severe asthma treatment: omalizumab, mepolizumab, reslizumab, benralizumab and dupilumab. These drugs have been shown to reduce exacerbations and to have an oral corticosteroid-sparing effect in many severe asthma patients. However, biological treatment is not successful in all patients and should be discontinued in non-responsive patients. Treating the right patient with the right biologic, and therefore biologic response prediction, has become a major point of interest in severe asthma management. A variety of response outcomes is utilized in the different clinical trials, as well as a huge range of potential predicting factors. Also, regarding the timing of the response evaluation, there are considerable differences between studies. This review summarizes the results from studies on predicting responses and responders to biological treatment in severe asthma, taking into account clinical, functional and inflammatory parameters assessed prior to the start of treatment as well as following a few months of therapy. In addition, future perspectives are discussed, highlighting the need for more research to improve patient identification and treatment responses in the field of biological treatment in severe asthma.

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Increase in systemic IL-5 is associated with mepolizumab treatment failure in patients with severe asthma

Cited by 5 publications

References 0 publications

Heterogeneous Response of Airway Eosinophilia to Anti-IL-5 Biologics in Severe Asthma Patients

Heterogeneous Response of Airway Eosinophilia to Anti-IL-5 Biologics in Severe Asthma Patients

Mepolizumab targets multiple immune cells in aspirin-exacerbated respiratory disease

Prediction of response to biological treatment with monoclonal antibodies in severe asthma

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