Effects of Anti-IL-13 (Novartis QAX576) on Inflammatory Responses Following Nasal Allergen Challenge (NAC).

Abstract

Introduction: IL−13 is a Th2 cytokine that has a potential pivotal role in allergic and asthmatic responses, including airway remodelling. Our objective was to evaluate the effects of anti−IL−13 on the inflammatory response following repetitive NAC in seasonal allergic rhinitis. Study design: A parallel group double−blind placebo−controlled study (n=16 and 15) with an open label group given topical nasal corticosteroids (n=5). Subjects received intranasal Timothy grass pollen (Phleum P5 allergen), and serial samples were taken using Synthetic Absorptive Matrix (Accuwik Ultra) and by nasal lavage. NAC was performed at screening and on days 5, 6 and 7 following infusion of anti−IL−13 or placebo. Results: Anti−IL−13 was found to profoundly inhibit levels of IL−13, and to a lesser extent eotaxin in SAM eluates during the late phase after NAC. However, there were no apparent effects on levels of nasal lavage eosinophils nor nasal symptom scores. In contrast, topical nasal corticosteroid caused pronounced suppression of IL−13, IL−5 and eotaxin in the late phase, inhibited the levels of lavage eosinophils, and decreased symptom scores in the late phase. Conclusions: Anti−IL−13 has specific pharmacodynamic target action, causing profound inhibition of nasal IL−13 responses. However, failure to inhibit nasal symptoms and eosinophils, suggests anti−IL−13 is not critical to the acute nasal allergic response. Further studies are now required to assess the effects of anti−IL−13 in asthma; and especially to elucidate effects on the airways in terms of inflammation, hyperreactivity and remodelling. This abstract is funded by: Novartis Pharmaceuticals.

Integrating mechanisms of pulmonary fibrosis

“…IL-1 ( Ingram et al, 2004 ), TGF-β1 ( Lee et al, 2001 ), adenosine ( Blackburn et al, 2003 ), chitinase family members ( Zhu et al, 2004 ; Lee et al, 2009 ), chemokines ( Belperio et al, 2002a ; Zhu et al, 2002 ; Ma et al, 2004 ), matrix metalloproteinases ( Lanone et al, 2002 ; Madala et al, 2010 ) and various fibroblast subsets ( Chiaramonte et al, 1999a ; Murray et al, 2008 ; Shao et al, 2008 ) are emerging as important targets of profibrotic IL-13. Together, these studies support recent efforts investigating the therapeutic potential of IL-13 antagonists in IPF and other chronic lung diseases ( Hariyawasam et al, 2009 ).…”

Let-7 microRNA–mediated regulation of IL-13 and allergic airway inflammation

“…Because of its wellestablished role in modulating T H 2 immune responses, including asthma, efforts are being made to therapeutically modulate IL-13 function. For instance, the anti-IL-13 antibodies, such as QAX576, were under clinical trials for the treatment of IL-13-related disorders 32 ; the human anti-IL-13 IgG 4 mAb CAT-354 has shown a significant reduction in airway eosinophilia and airway reactivity in a murine model of airway and esophageal inflammation. 33 The aim of this study was to explore the molecular events underlying posttranscriptional regulation of IL-13 in patients with asthma and related disorders.…”

Investigational therapeutics targeting the IL-4/IL-13/STAT-6 pathway for the treatment of asthma

“…Evidence from animal models supported the use of a number of pharmaceutical IL-13 neutralising antibodies (table 2) KARIYAWASAM et al [62] studied the effects of the anti-IL-13 monoclonal antibody, QAX576, on inflammatory responses following nasal allergen challenges in patients with seasonal allergic rhinitis. This was a parallel-group, double-blind, placebo-controlled study (n516), with an open-label phase (n55) of topical nasal corticosteroids being administered.…”