Baseline serum CXCL10 and IL-12 levels may predict severe asthmatics' responsiveness to omalizumab

Suzukawa, Maho; Matsumoto, Hisako; Ohshima, Nobuharu; Tashimo, Hiroyuki; Asari, Isao; Tajiri, Tomoko; Niimi, Akio; Nagase, Hiroyuki; Matsui, Hirotoshi; Kobayashi, Nobuyuki; Shoji, Shunsuke; Ohta, Ken

doi:10.1016/j.rmed.2017.12.002

Cited by 19 publications

(18 citation statements)

References 30 publications

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“…25 For instance, when data from patients only treated with omalizumab were considered in the Study of Omalizumab (Xolair) in Subjects with Moderate to Severe Persistent Asthma (EXTRA), no substantial difference in exacerbation frequency between the high and low EoS and FeNO subgroups were observed, suggesting that all patients can benefit from omalizumab treatment irrespective of biomarker status. 25 Literature has reported that other biomarkers, such as IgE, 35e37 periostin, 38 C-X-C motif chemokine 10, 39 and interleukin-12, 39 may also be of importance for patients treated with omalizumab.…”

Section: Discussionmentioning

confidence: 99%

Retrospective Study on the Association of Biomarkers With Real-world Outcomes of Omalizumab-treated Patients With Allergic Asthma

Kavati

Zhdanava

Ortiz

et al. 2019

Clinical Therapeutics

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Purpose: Biomarkers, including blood eosinophils (EoS) and fractional exhaled nitric oxide (FeNO), may affect omalizumab outcomes in allergic asthma, but evidence in the literature remains mixed. This study assessed omalizumab outcomes in real-world patients with allergic asthma stratified by pretreatment biomarker levels. Methods: Patients with allergic asthma aged 12 years initiated on omalizumab with 12 months of data after index were identified in the Allergy Partners electronic medical records (2007e2018). Patients with 1 diagnosis of chronic obstructive pulmonary disease in combination with 10 pack-years of smoking, cystic fibrosis, Alpha-1 antitrypsin deficiency, bronchiectasis, interstitial lung disease, and sarcoidosis in the 12 months before or after index were excluded. Patients were stratified by pretreatment EoS (/<300 cells/mL) and FeNO (/<25 parts per billion). Outcomes, including Asthma Control Test (ACT) scores, forced expiratory volume in 1 second (FEV 1), and FEV 1 as a percentage of predicted value (FEV 1 % predicted), were compared using generalized estimating equations at 6 and 12 months after versus before index date in stratified patients with outcome measures available at both time periods. Findings: A total of 77 and 86 patients were stratified into the high and low EoS strata, respectively, and 56 patients into each of the intermediate-high and low FeNO strata. Compared with 6 months before index, mean difference (MD) in ACT scores at 6 months after index reached the minimally important difference of 3 points in high (MD ¼ 3.75; 95% CI, 2.05e5.45) and

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Section: Discussionmentioning

confidence: 99%

Retrospective Study on the Association of Biomarkers With Real-world Outcomes of Omalizumab-treated Patients With Allergic Asthma

Kavati

Zhdanava

Ortiz

et al. 2019

Clinical Therapeutics

View full text Add to dashboard Cite

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“…Clinical markers, including IgE levels, blood eosinophil count and exhaled nitric oxide (Fe NO ) [7], are often a predictor of response and an indicator to which specific biological should be administered; however, a more complete profile is necessary to increase accuracy. For example, for omalizumab, the first approved biological targeting IgE, it was recently shown that a high baseline level of serum CXCL10 and IL-12 is predictive of a response to the treatment in severe asthma [8]. This not only predicts which patient groups benefit the most but also highlights the existence of different endotypes in allergy and asthma and the need for a more personalized approach in treating them.…”

Section: Biologicals Targeting Th2-type Immune Responses: Successful Translation From Bench To Bedsidementioning

confidence: 99%

Modulating local airway immune responses to treat allergic asthma: lessons from experimental models and human studies

et al. 2020

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With asthma affecting over 300 million individuals world-wide and estimated to affect 400 million by 2025, developing effective, long-lasting therapeutics is essential. Allergic asthma, where Th2-type immunity plays a central role, represents 90% of child and 50% of adult asthma cases. Research based largely on animal models of allergic disease have led to the generation of a novel class of drugs, so-called biologicals, that target essential components of Th2-type inflammation. Although highly efficient in subclasses of patients, these biologicals and other existing medication only target the symptomatic stage of asthma and when therapy is ceased, a flare-up of the disease is often observed. Therefore, it is suggested to target earlier stages in the inflammatory cascade underlying allergic airway inflammation and to focus on changing and redirecting the initiation of type 2 inflammatory responses against allergens and certain viral agents. This focus on upstream aspects of innate immunity that drive development of Th2-type immunity is expected to have longer-lasting and disease-modifying effects, and may potentially lead to a cure for asthma. This review highlights the current understanding of the contribution of local innate immune elements in the development and maintenance of inflammatory airway responses and discusses available leads for successful targeting of those pathways for future therapeutics.

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“…More recently, a humanized anti-IgE antibody, omalizumab, has been developed to prevent binding of circulating IgE to FcεRI and the downstream effects of cross-linking ( 218 , 219 ). Omalizumab is a common and preferred treatment for chronic urticaria ( 220 , 221 ) and shows efficacy for the treatment of asthma ( 218 , 219 ); however, like many drugs, there appear to be responders and non-responders ( 222 ). These drugs represent both progress toward suppressing mast cell function and shortcomings supporting further development.…”

Section: Therapeutics Targeting Mast Cellsmentioning

confidence: 99%

Controlling Mast Cell Activation and Homeostasis: Work Influenced by Bill Paul That Continues Today

et al. 2018

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Mast cells are tissue resident, innate immune cells with heterogenous phenotypes tuned by cytokines and other microenvironmental stimuli. Playing a protective role in parasitic, bacterial, and viral infections, mast cells are also known for their role in the pathogenesis of allergy, asthma, and autoimmune diseases. Here, we review factors controlling mast cell activation, with a focus on receptor signaling and potential therapies for allergic disease. Specifically, we will discuss our work with FcεRI and FγR signaling, IL-4, IL-10, and TGF-β1 treatment, and Stat5. We conclude with potential therapeutics for allergic disease. Much of these efforts have been influenced by the work of Bill Paul. With many mechanistic targets for mast cell activation and different classes of therapeutics being studied, there is reason to be hopeful for continued clinical progress in this area.

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Baseline serum CXCL10 and IL-12 levels may predict severe asthmatics' responsiveness to omalizumab

Abstract: High baseline serum CXCL10 and IL-12 levels may be useful in predicting a good omalizumab response in severe asthmatics.

Cited by 19 publications

References 30 publications

Retrospective Study on the Association of Biomarkers With Real-world Outcomes of Omalizumab-treated Patients With Allergic Asthma

Retrospective Study on the Association of Biomarkers With Real-world Outcomes of Omalizumab-treated Patients With Allergic Asthma

Modulating local airway immune responses to treat allergic asthma: lessons from experimental models and human studies

Controlling Mast Cell Activation and Homeostasis: Work Influenced by Bill Paul That Continues Today

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