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Bronchus-associated lymphoid tissue and immune-mediated respiratory diseases
Published in Phillip D. Smith, Richard S. Blumberg, Thomas T. MacDonald, Principles of Mucosal Immunology, 2020
Dale T. Umetsu, Bart Lambrecht
Several monoclonal antibodies against IL-13 (lebrikizumab, Dermira and tralokinumab, AstraZeneca) are being studied for the treatment of atopic diseases, including asthma and atopic dermatitis. IL-13 has been shown to be an important effector molecule in asthma and allergic disease.
IgE-mediated (immediate) hypersensitivity
Published in Gabriel Virella, Medical Immunology, 2019
Albert F. Finn, Gabriel Virella
In patients with atopic dermatitis, anti-IL-31 monoclonal antibodies (nemolizumab, tralokinumab) and dupilumab, a monoclonal antibody that blocks the IL-4Rα receptor subunit shared by the receptor of both IL-4 and IL-13, are currently being evaluated with preliminary encouraging results.
Management of idiopathic pulmonary fibrosis
Published in Muhunthan Thillai, David R Moller, Keith C Meyer, Clinical Handbook of Interstitial Lung Disease, 2017
Damian AD Bruce-Hickman, Helen Garthwaite, Melissa Heightman, Bibek Gooptu
The cytokine, IL-13, correlates inversely with FVC in IPF patients (150) and may be important in those who experience rapid progression (151). Inhibition of IL-13 in humanized models of IPF results in reduced extracellular matrix deposition and reduced epithelial cell apoptosis. Monoclonal antibodies directed against IL-13 (lebrikizumab, tralokinumab) have been used in phase 2 trials. The trial of tralokinumab for IPF (ClinicalTrials.gov NCT01629667) was halted early due to lack of efficacy. The lebrikizumab trial will assess the effects of the drug compared with placebo, both alone and in combination with pirfenidone (ClinicalTrials.gov NCT01872689). An additional agent, SAR156597, that targets both IL-4 and IL-13 is also in phase 2 studies (ESTAIR, ClinicalTrials.gov NCT02345070).
Investigational anti IL-13 asthma treatments: a 2023 update
Published in Expert Opinion on Investigational Drugs, 2023
Maria Gabriella Matera, Josuel Ora, Luigino Calzetta, Paola Rogliani, Mario Cazzola
Tralokinumab was then assessed in a phase IIb study with 452 patients with severe asthma to determine whether it might reduce the number of exacerbations [38]. Tralokinumab was administered subcutaneously for 52 weeks at 300 mg every two weeks or 300 mg every two weeks for 12 weeks, followed by 300 mg every four weeks; the latter dosing regimen proved ineffective. Both regimens did not affect the overall exacerbation rate. Nevertheless, in the high dipeptidyl peptidase-4 and high periostin subgroups, individuals receiving tralokinumab every 2 weeks reported non-significant decreases in annualized asthma exacerbation rate (AAER) compared to placebo (−34% and −27%, respectively) at week 52. Furthermore, FEV1 improvement was largest in those patients given tralokinumab every two weeks, especially if they had a combination of elevated biomarker concentration, post-bronchodilator reversibility, and absence of long-term oral corticosteroids (OCS).
Shedding light on key pharmacological knowledge and strategies for pediatric atopic dermatitis
Published in Expert Review of Clinical Pharmacology, 2023
Ariana Moreno, Yael Renert-Yuval, Emma Guttman-Yassky
Tralokinumab is an IL-13 antagonist human IgG4 monoclonal antibody that functions by blocking IL-13Rα1 and IL-13Rα2 from binding to IL-13, inhibiting downstream effects of this Th2 cytokine [121,122]. Tralokinumab is currently only approved for the treatment of moderate-to-severe AD in adults. However, a phase III clinical trial analyzing the efficacy and safety of tralokinumab in patients aged 12–17 found that at week 16 more patients receiving either 150 mg or 300 mg every 2 weeks reported IGA 0/1 and EASI-75 compared to placebo [123]. Additionally, at week 16, patients receiving tralokinumab reported an NRS improvement >4 points. The tralokinumab group also reported greater improvements in SOCRAD and quality-of-life measures compared to placebo at week 16 [123]. Its efficacy in children is to comparable to that in adults. The most common reported adverse effects with tralokinumab use reported in adults include conjunctivitis, upper respiratory infections, and headaches [124–126].
Biological agents targeting interleukin-13 for atopic dermatitis
Published in Expert Opinion on Biological Therapy, 2022
Andrea Chiricozzi, Niccolò Gori, Martina Maurelli, Paolo Gisondi, Giacomo Caldarola, Clara De Simone, Ketty Peris, Giampiero Girolomoni
Pre-clinical evidence has clarified the tralokinumab spectrum-of-action [56,57]. In particular, an in vitro cell culture-based study revealed the inhibitory activity of tralokinumab against IL-13 [57]. Primary human epidermal keratinocytes and human dermal fibroblasts stimulated with IL-13 showed altered expression of a subset of genes related to type-2 inflammation and skin-barrier formation [57]. IL-13 upregulated genes related to type-2 inflammation (i.e. CCL2, CCL17, CCL22, and CCL26) and downregulated genes related to terminal keratinocyte differentiation (i.e. filaggrin and loricrin). These expression levels were fully normalized by treatment with tralokinumab, but not an isotype control antibody, suggesting that tralokinumab can restore skin-barrier alterations and suppress skin inflammation [57]. The clinical benefits associated with tralokinumab use have been described in both phase II and phase III trials, confirming these pre-clinical findings.