Therapeutical Targets in Allergic Inflammation

Liotta, Francesco; Annunziato, Francesco; Cosmi, Lorenzo

doi:10.3390/biomedicines10112874

Cited by 11 publications

(8 citation statements)

References 161 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Dupilumab, a monoclonal antibody targeting the shared IL-4 receptor a (IL-4Ra) that inhibits both IL-4 and IL-13, has demonstrated its efficacy and safety in clinical trials and realworld studies (5)(6)(7)(8)(9)(10)(11)(12). Currently, it is the first biologics approved for the treatment of moderate-to-severe AD in patients aged ≥6 months (13). However, due to the strict inclusion criteria of clinical trials, the actual conditions of dupilumab in the real world are not reflected in the studies.…”

Section: Introductionmentioning

confidence: 99%

High loading-dose of dupilumab resulted in rapid disease control in pediatric patients with atopic dermatitis

et al. 2023

View full text Add to dashboard Cite

BackgroundThe real-world experience of dupilumab in Chinese is limited, and the initial loading dose has not yet been deeply explored in patients aged <6 years.ObjectiveTo explore the efficacy and safety of dupilumab in Chinese patients with moderate-to-severe atopic dermatitis and investigate the effect of higher loading dose for disease control in patients aged <6 years.MethodsA total of 155 patients were divided into three groups according to age: <6 years, 6-11 years, and >11 years. Among patients aged <6 years, 37 patients received a high loading dose of 300 mg for body weight <15kg or 600 mg for body weight ≥15kg, and another 37 patients received a standard loading dose of 200 mg for body weight <15kg or 300 mg for body weight ≥15kg. Multiple physicians and patient-reported outcome measures were evaluated at baseline and 2, 4, 6, 8, 12, and 16 weeks after dupilumab treatment.ResultsThe proportion of patients showing an improvement of ≥75% in the Eczema Area and Severity Index was 68.0% (17/25), 76.9% (10/13), and 62.5% (25/40) in the aged <6, 6-11, and >11 years groups, respectively, at week 16. After increasing the loading dose, 69.6% (16/23) of patients aged <6 years achieved 4-point improvement in Pruritus Numerical Rating Scale at week 2, compared with 23.5% (8/34) of patients receiving standard loading dose (P < 0.001). Obesity (odds ratio=0.12, 95% confidence interval: 0.02-0.70) was predictive of a poor response to dupilumab treatment, while female (odds ratio=3.94, 95% confidence interval: 1.26-12.31) predicted good response at week 16. The change of serum C-C motif ligand 17(CCL17/TARC) could reflect the response to dupilumab (r = 0.53, P = 0.002 in EASI) among patients aged <18 years. No major adverse events were reported during the treatment.ConclusionsDupilumab was effective and well-tolerated in Chinese patients with atopic dermatitis. The increased loading dose helped achieve rapid pruritus control in patients aged <6 years.

show abstract

Section: Introductionmentioning

confidence: 99%

High loading-dose of dupilumab resulted in rapid disease control in pediatric patients with atopic dermatitis

et al. 2023

View full text Add to dashboard Cite

show abstract

“…Similarly, direct blockade of the effector cytokine IL-17A or its receptor IL-17RA has proven highly efficacious in psoriasis and other Th17 cell-mediated diseases [96]. Along with strategies targeting inducing, enhancing and effector cytokines of pathogenic Th cells, monoclonal antibodies targeting Th2 effector cytokines (IL-4Rα, IL-4, and IL-13) have also entered the clinic with great success in the treatment of atopic dermatitis and asthma [97,98]. IL-13, in particular, increases mucus production and goblet cell hyperplasia, stimulates the activity of bronchial smooth muscle cells and promotes the extracellular deposition of collagen, thus promoting airway remodeling in asthma [99].…”

Section: Th Cells In Tissuesmentioning

confidence: 99%

T helper cell subsets: diversification of the field

Zielinski

2023

Eur J Immunol

View full text Add to dashboard Cite

Polarized T helper cell (Th cell) responses are important determinants of host protection. Th cell subsets tailor their functional repertoire of cytokines to their cognate antigens to efficiently contribute to their clearance. In contrast, in settings of immune abrogation, these polarized cytokine patterns of Th cells can mediate tissue damage and pathology resulting in allergy or autoimmunity. Recent technological developments in single‐cell genomics and proteomics as well as advances in the high‐dimensional bioinformatic analysis of complex datasets have challenged the prevailing Th cell subset classification into Th1, Th2, Th17, and other subsets. Additionally, systems immunology approaches have revealed that instructive input from the peripheral tissue microenvironment can have differential effects on the overall phenotype and molecular wiring of Th cells depending on their spatial distribution. Th cells from the blood or secondary lymphoid organs are therefore expected to follow distinct rules of regulation. In this review, the functional heterogeneity of Th cell subsets will be reviewed in the context of new technological developments and T‐cell compartmentalization in tissue niches. This work will especially focus on challenges to the traditional boundaries of Th cell subsets and will discuss the underlying regulatory checkpoints, which could reveal new therapeutic strategies for various immune‐mediated diseases.

show abstract

“…7,9-12 Among them, omalizumab, an anti-IgE antibody, and dupilumab, an anti-IL-4Rα antibody, are most likely to target allergic inflammation, due to their modes of action and pleiotropic effects on allergic inflammation. 13 Current GINA guidelines recommend the use of an anti-IgE monoclonal antibody (omalizumab) in patients with allergic asthma. 1 It is worth noting that, in previous analyses of dupilumab asthma studies, including QUEST, dupilumab reduced the rate of severe exacerbations, improved lung function, and improved asthma control in patients with non-OCS-dependent, moderateto-severe asthma with or without evidence of allergic asthma.…”

Section: Introductionmentioning

confidence: 99%

“…Several biologic therapies are available for the treatment of asthma 7,9–12 . Among them, omalizumab, an anti‐IgE antibody, and dupilumab, an anti‐IL‐4Rα antibody, are most likely to target allergic inflammation, due to their modes of action and pleiotropic effects on allergic inflammation 13 . Current GINA guidelines recommend the use of an anti‐IgE monoclonal antibody (omalizumab) in patients with allergic asthma 1 .…”

Section: Introductionmentioning

confidence: 99%

Dupilumab improves long‐term outcomes in patients with uncontrolled, moderate‐to‐severe GINA‐based type 2 asthma, irrespective of allergic status

Rabe

Pavord

Busse

et al. 2023

Allergy

View full text Add to dashboard Cite

Background: Previous research has shown greater efficacy of dupilumab in patients with uncontrolled asthma and type 2 inflammation. We analyzed dupilumab's efficacy in patients from the TRAVERSE study with or without evidence of allergic asthma and type 2 inflammation per current GINA guidelines (≥150 eosinophils/μL or FeNO ≥20 ppb).Methods: All patients aged ≥12 years who rolled over from the placebo-controlled QUEST study (NCT02414854) to TRAVERSE (NCT02134028) received add-on dupilumab 300 mg every 2 weeks for up to 96 weeks. We assessed annualized severe asthma exacerbation rates (AERs) and changes from parent-study baseline (PSBL) in pre-bronchodilator FEV 1 and 5-item asthma control questionnaire (ACQ-5) score in patients with moderate-to-severe type 2 asthma with and without evidence of allergic asthma at PSBL. Results:In TRAVERSE, dupilumab consistently reduced AER across all subgroups.By Week 96, dupilumab increased pre-bronchodilator FEV 1 from PSBL by 0.35-0.41 L in patients receiving placebo during QUEST (placebo/dupilumab) and 0.34-0.44 L in those receiving dupilumab during QUEST (dupilumab/dupilumab) with an allergic phenotype at baseline. In patients without evidence of allergic asthma, prebronchodilator FEV 1 improved by 0.38-0.41 L and 0.33-0.37 L, respectively. By Week 48, ACQ-5 scores decreased from PSBL by 1.63-1.69 (placebo/dupilumab) and 1.74-1.81 (dupilumab/dupilumab) points across subgroups with allergic asthma, and 1.75-1.83 (placebo/dupilumab) and 1.78-1.86 (dupilumab/dupilumab) in those without. Conclusions:Long-term treatment with dupilumab reduced exacerbation rates and improved lung function and asthma control in patients with asthma with type 2 inflammation as per current GINA guidance and irrespective of evidence of allergic asthma.

show abstract

Therapeutical Targets in Allergic Inflammation

Cited by 11 publications

References 161 publications

High loading-dose of dupilumab resulted in rapid disease control in pediatric patients with atopic dermatitis

High loading-dose of dupilumab resulted in rapid disease control in pediatric patients with atopic dermatitis

T helper cell subsets: diversification of the field

Dupilumab improves long‐term outcomes in patients with uncontrolled, moderate‐to‐severe GINA‐based type 2 asthma, irrespective of allergic status

Contact Info

Product

Resources

About