The potential of biologics for the treatment of asthma (original) (raw)
Holgate, S. T. et al. A new look at the pathogenesis of asthma. Clin. Sci.118, 439–450 (2010). CAS Google Scholar
Anderson, G. P. Endotyping asthma: new insights into key pathogenetic mechanisms in a complex, heterogeneous disease. Lancet372, 1107–1119 (2008). PubMed Google Scholar
Global Initiative for Asthma (GINA). Global strategy for asthma management and prevention. GINA[online], (2005).
Bateman, E. D. et al. Can guideline-defined asthma control be achieved? The Gaining Optimal Asthma ControL (GOAL) study. Am. J. Respir. Crit. Care Med.170, 836–844 (2004). PubMed Google Scholar
Fanta, C. H. Drug therapy: asthma. N. Engl. J. Med.360, 1002–1014 (2009). CASPubMed Google Scholar
Boulet, L. P. Influence of comorbid conditions on asthma. Eur. Respir. J.33, 897–906 (2009). PubMed Google Scholar
Serra-Batlles, J., Plaza, V., Morejon, E., Comella, A. & Brugues, J. Costs of asthma according to the degree of severity. Eur. Respir. J.12, 1322–1326 (1998). CASPubMed Google Scholar
Heaney, L. G. et al. Predictors of therapy resistant asthma: outcome of a systematic evaluation protocol. Thorax58, 561–566 (2003). CASPubMedPubMed Central Google Scholar
Dolan, C. M. et al. Design of baseline characteristics of the epidemiology and natural history of asthma: outcomes and treatment regimens (TENOR) study: a large cohort of patients with severe or difficult-to-treat asthma. Ann. Allergy Asthma Immunol.92, 32–39 (2004). PubMed Google Scholar
Haselkorn, T., Borish, L., Miller, D. P., Weiss, S. T. & Wong, D. A. High prevalence of skin test positivity in severe or difficult-to-treat asthma. J. Asthma43, 745–752 (2006). CASPubMed Google Scholar
Gould, H. J. & Sutton, B. J. IgE in allergy and asthma today. Nature Rev. Immunol.8, 205–217 (2008). CAS Google Scholar
Barnes, P. J. The cytokine network in asthma and chronic obstructive pulmonary disease. J. Clin. Invest.118, 3546–3556 (2008). CASPubMedPubMed Central Google Scholar
Al-Ramly, W. et al. TH17-associated cytokines (IL-17A and IL-17F) in severe asthma. J. Allergy Clin. Immunol.123, 1185–1187 (2009). Google Scholar
Walsh, G. M. Novel cytokine-directed therapies for asthma. Discov. Med.11, 283–291 (2011). PubMed Google Scholar
Gruenberg, D. & Busse, W. Biologic therapies for asthma. Curr. Opin. Pulm. Med.16, 19–24 (2010). PubMed Google Scholar
Rodrigo, G. J., Neffen, H. & Castro-Rodriguez, J. A. Efficacy and safety of subcutaneous omalizumab versus placebo as add-on therapy to corticosteroids for children and adults with asthma: a systematic review. Chest139, 28–35 (2011). CASPubMed Google Scholar
Hansbro, P. M., Kaiko, G. E. & Foster, P. S. Cytokine/anti-cytokine therapy — novel treatments for asthma? Br. J. Pharmacol.163, 81–95 (2011). CASPubMedPubMed Central Google Scholar
Bouzigon, E. et al. Effect of 17q21 variants and smoking exposure in early-onset asthma. N. Engl. J. Med.359, 1985–1994 (2008). CASPubMed Google Scholar
Wenzel, S. E. Asthma phenotypes: the evolution from clinical to molecular approaches. Nature Med.18, 716–725 (2012). CASPubMed Google Scholar
Moore, W. C. et al. Characterization of the severe asthma phenotype by the National Heart, Lung, and Blood Institute's Severe Asthma Research Program. J. Allergy Clin. Immunol.119, 405–413 (2007). PubMedPubMed Central Google Scholar
Phelan, P. D., Robertson, C. F. & Olinsky, A. The Melbourne Asthma Study: 1964–1999. J. Allergy Clin. Immunol.109, 89–94 (2002). Google Scholar
Wenzel, S. Severe asthma: from characteristics to phenotypes to endotypes. Clin. Exp. Allergy42, 650–658 (2012). CASPubMed Google Scholar
Barrett, N. A. & Austen, K. F. Innate cells and T helper 2 cell immunity in airway inflammation. Immunity31, 425–437 (2009). CASPubMedPubMed Central Google Scholar
Woodruff, P. G. et al. Th2-driven inflammation defines major sub-phenotypes of asthma. Am. J. Respir. Crit. Care Med.180, 388–395 (2009). This study is a cornerstone in the efforts aimed at characterizing the various asthma phenotypes and the different underlying mechanisms. CASPubMedPubMed Central Google Scholar
Corren, J. et al. Lebrikizumab treatment in adults with asthma. N. Engl. J. Med.365, 1088–1098 (2011). This important study suggests that it is possible to use the IL-13-specific monoclonal antibody lebrikizumab for the treatment of patients with specific asthma phenotypes, who are selected on the basis of the expression of appropriate biomarkers such as periostin. CASPubMed Google Scholar
Sokol, C. L., Barton, G. M., Farr, A. G. & Medzhitov, R. A mechanism for the initiation of allergen-induced T helper type 2 responses. Nature Immunol.9, 310–318 (2008). CAS Google Scholar
Ying, S. et al. Thymic stromal lymphopoietin expression is increased in asthmatic airways and correlates with expression of Th2-attracting chemokines and disease severity. J. Immunol.174, 8183–8190 (2005). CASPubMed Google Scholar
Nguyen, K. D., Vanichsarn, C. & Nadeau, K.C. TSLP directly impairs pulmonary Treg function: association with aberrant tolerogenic immunity in asthmatic airway. Allergy Asthma Clin. Immunol.6, 4 (2010). CASPubMedPubMed Central Google Scholar
Hamid, Q. & Tulic, M. Immunobiology of asthma. Annu. Rev. Physiol.71, 489–507 (2009). CASPubMed Google Scholar
Collins, P. D., Marleau, S., Griffiths-Johnson, D. A., Jose, P. J. & Williams, T. J. Cooperation between interleukin-5 and the chemokine eotaxin to induce eosinophil accumulation in vivo. J. Exp. Med.182, 1169–1174 (1995). CASPubMed Google Scholar
Zietkowski, Z., Tomasiak, M. M., Skiepko, R. & Bodzenta-Lukaszyk, A. RANTES in exhaled breath condensate of stable and unstable asthma patients. Respir. Med.102, 1198–2202 (2008). CASPubMed Google Scholar
Finkelman, F. et al. IL-4 is required to generate and sustain in vivo IgE responses. J. Immunol.141, 2335–2341 (1988). CASPubMed Google Scholar
Grunig, G. et al. Requirement for IL-13 independently of IL-4 in experimental asthma. Science282, 2261–2263 (1998). CASPubMedPubMed Central Google Scholar
Veldohen, M. et al. Transforming growth factor-β 'reprograms' the differentiation of T helper 2 cells and promotes an interleukin 9-producing subset. Nature Immunol.9, 1341–1346 (2008). Google Scholar
Chang, H. C. et al. The transcription factor PU.1 is required for the development of IL-9-producing T cells and allergic inflammation. Nature Immunol.11, 527–534 (2010). CAS Google Scholar
The ENFUMOSA Study Group. The ENFUMOSA cross-sectional European multicentre study of the clinical phenotype of chronic severe asthma. Eur. Respir. J.22, 470–477 (2003).
Zhao, Y., Yang, J., Gao, Y. D. & Guo, W. Th17 immunity in patients with allergic asthma. Int. Arch. Allergy Immunol.151, 297–307 (2010). CASPubMed Google Scholar
Lukacs, N. W., Strieter, R. M., Chensue, S. W., Widmer, M. & Kunkel, S. L. TNF-α mediates recruitment of neutrophils and eosinophils during airway inflammation. J. Immunol.154, 5411–5417 (1995). CASPubMed Google Scholar
Amrani, Y., Panettieri, R. A. Jr., Frossard, N. & Bronner, C. Activation of the TNF-α-p55 receptor induces myocyte proliferation and modulates agonist-evoked calcium transients in cultured human tracheal smooth muscle cells. Am. J. Respir. Cell. Mol. Biol.15, 55–63 (1996). CASPubMed Google Scholar
ten Brinke, A. et al. Risk factors of frequent exacerbations in difficult-to-treat asthma. Eur. Respir. J.26, 812–818 (2005). CASPubMed Google Scholar
Contoli, M. & et al. Role of deficient type III interferon-λ production in asthma exacerbations. Nature Med.12, 1023–1026 (2006). CASPubMed Google Scholar
Matsumoto, K. et al. Frequency of Foxp3+CD4+CD25+ T cells is associated with the phenotypes of allergic asthma. Respirology14, 187–194 (2009). PubMed Google Scholar
Provoost, S. et al. Decreased FOXP3 protein expression in patients with asthma. Allergy64, 1539–1546 (2009). CASPubMed Google Scholar
Abdulamir, A. S. et al. Severity of asthma: the role of CD25+, CD30+, NF-κB, and apoptotic markers. J. Investig. Allergol. Clin. Immunol.19, 218–224 (2009). CASPubMed Google Scholar
Turato, G. et al. Nonatopic children with multitrigger wheezing have airway pathology comparable to atopic asthma. Am. J. Respir. Crit. Care Med.178, 476–482 (2008). PubMed Google Scholar
Jeffery, P. K. Remodeling in asthma and chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med.164, S28–S38 (2001). CASPubMed Google Scholar
Tliba, O. & Panettieri, R. A. Jr. Noncontractile functions of airway smooth muscle in asthma. Annu. Rev. Physiol.71, 509–535 (2009). CASPubMed Google Scholar
Payne, D. N. et al. Early thickening of the reticular basement membrane in children with difficult asthma. Am. J. Respir. Crit. Care Med.167, 78–82 (2003). PubMed Google Scholar
Saglani, S. et al. Early detection of airway wall remodeling and eosinophilic inflammation in preschool wheezers. Am. J. Respir. Crit. Care Med.176, 858–864 (2007). PubMed Google Scholar
Ebina, M., Takahashi, T., Chiba, T. & Motomiya, M. Cellular hypertrophy and hyperplasia of airway smooth muscle underlying bronchial asthma. A 3D morphometric study. Am. Rev. Respir. Dis.148, 720–726 (1993). CASPubMed Google Scholar
Bai, T. R., Cooper, J., Koelmeyer, T., Pare, P. D. & Weir, T. D. The effect of age and duration of disease on airway structure in fatal asthma. Am. J. Respir. Crit. Care Med.162, 663–669 (2000). CASPubMed Google Scholar
Salvato, G. Quantitative and morphological analysis of the vascular bed in bronchial biopsy specimens from asthmatic and non-asthmatic subjects. Thorax56, 902–906 (2001). CASPubMedPubMed Central Google Scholar
Hoshino, M., Takahashi, M. & Aoike, N. Expression of vascular endothelial growth factor, basic fibroblast growth factor, and angiogenin immunoreactivity in asthmatic airways and its relationship to angiogenesis. J. Allergy Clin. Immunol.107, 295–301 (2001). CASPubMed Google Scholar
Hastie, A. T. et al. Asthmatic epithelial cell proliferation and stimulation of collagen production: human asthmatic epithelial cells stimulate collagen type III production by human lung fibroblasts after segmental allergen challenge. Am. J. Respir. Crit. Care Med.165, 266–272 (2002). PubMed Google Scholar
Hackett, T. L. et al. Induction of epithelial-mesenchymal transition in primary airway epithelial cells from patients with asthma by transforming growth factor-β1. Am. J. Respir. Crit. Care Med.180, 122–133 (2009). CASPubMed Google Scholar
Heijink, I. H., Postma, D. S., Noordhoek, J. A., Broekma, M. & Kapus, A. House dust mite-promoted epithelial-to-mesenchymal transition in human bronchial epithelium. Am. J. Respir. Cell. Mol. Biol.42, 69–79 (2010). CASPubMed Google Scholar
Vignola, A. M. et al. Transforming growth factor-β expression in mucosal biopsies in asthma and chronic bronchitis. Am. J. Respir. Crit. Care Med.156, 591–599 (1997). CASPubMed Google Scholar
Doherty, T. & Broide, D. Cytokines and growth factors in airway remodeling in asthma. Curr. Opin. Immunol.19, 676–680 (2007). CASPubMed Google Scholar
Pascual, R. M. & Peters, S. P. Airway remodeling contributes to the progressive loss of lung function in asthma: an overview. J. Allergy Clin. Immunol.116, 477–486 (2005). PubMed Google Scholar
Ishizaka, K. & Ishizaka, T. Identification of γE antibodies as a carrier of reaginic activity. J. Immunol.99, 1187–1198 (1967). CASPubMed Google Scholar
Pelaia, G., Renda, T., Romeo, P., Busceti, M. T. & Maselli, R. Omalizumab in the treatment of severe asthma: efficacy and current problems. Ther. Adv. Respir. Res.2, 409–421 (2008). Google Scholar
Presta, L. G. et al. Humanization of an antibody directed against IgE. J. Immunol.151, 2623–2632 (1993). CASPubMed Google Scholar
Rivera, J. & Gilfillan, A. M. Molecular regulation of mast cell activation. J. Allergy Clin. Immunol.117, 1214–1225 (2006). CASPubMed Google Scholar
Galli, S. J. & Tsai, M. IgE and mast cells in allergic disease. Nature Med.18, 693–704 (2012). CASPubMed Google Scholar
Shields, R. L. et al. Inhibition of allergic reactions with antibodies to IgE. Int. Arch. Allergy Immunol.107, 308–312 (1995). CASPubMed Google Scholar
Holgate, S. et al. The anti-inflammatory effects of omalizumab confirm the central role of IgE in allergic inflammation. J. Allergy Clin. Immunol.115, 459–465 (2005). CASPubMed Google Scholar
Novak, N. et al. Evidence for a differential expression of the FcɛRIγ chain in dendritic cells of atopic and non atopic donors. J. Clin. Invest.111, 1047–1056 (2003). CASPubMedPubMed Central Google Scholar
Campbell, A. M. et al. Expression of the high-affinity receptor for IgE on bronchial epithelial cells of asthmatics. Am. J. Respir. Cell. Mol. Biol.19, 92–97 (1998). CASPubMed Google Scholar
Gounni, A. S. et al. Human airway smooth muscle cells express the high affinity receptor for IgE (FcɛRI): a critical role of FcɛRI in human airway smooth muscle function. J. Immunol.175, 2613–2621 (2005). CASPubMed Google Scholar
Huang, Y. C., Leyko, B. & Frier, M. Effects of omalizumab and budesonide on markers of inflammation in human bronchial epithelial cells. Ann. Allergy Asthma Immunol.95, 443–451 (2005). CASPubMed Google Scholar
Zietkowski, Z., Skiepko, R., Tomasiak-Lozowska, M. M. & Bodzenta-Lukaszyk, A. Anti-IgE therapy with omalizumab decreases endothelin-1 in exhaled breath condensate of patients with severe persistent allergic asthma. Respiration80, 534–542 (2010). CASPubMed Google Scholar
Hoshino, M. & Ohtawa, J. Effects of adding omalizumab, an anti-immunoglobulin E antibody, on airway wall thickening in asthma. Respiration83, 520–528 (2012). CASPubMed Google Scholar
Riccio, A. M. et al. Omalizumab modulates bronchial reticular basement membrane thickness and eosinophil infiltration in severe persistent allergic asthma patients. Int. J. Immunopathol. Pharmacol.25, 475–484 (2012). This very interesting study, carried out in patients with severe persistent allergic asthma, shows that the use of omalizumab as an add-on treatment for 1 year can modulate airway remodelling by reducing the thickness of the airway RBM. CASPubMed Google Scholar
Stirling, R. G., van Rensen, E. I., Barnes, P. J. & Chung, K. F. Interleukin-5 induces CD34+ eosinophil progenitor mobilization and eosinophil CCR3 expression in asthma. Am. J. Respir. Crit. Care Med.164, 1403–1409 (2001). CASPubMed Google Scholar
Garlisi, C. G. et al. Effects of chronic anti-interleukin-5 monoclonal antibody treatment in a murine model of pulmonary inflammation. Am. J. Respir. Cell. Mol. Biol.20, 248–255 (1999). CASPubMed Google Scholar
Mauser, P. et al. Effects of an antibody to interleukin-5 in a monkey model of asthma. Am. J. Respir. Crit. Care Med.152, 467–472 (1995). CASPubMed Google Scholar
Molfino, N. A., Gossage, D., Kolbeck, R., Parker, J. M. & Geba, G. P. Molecular and clinical rationale for therapeutic targeting of interleukin-5 and its receptor. Clin. Exp. Allergy42, 712–737 (2012). CASPubMed Google Scholar
Leckie, M. et al. Effects of an interleukin-5 blocking monoclonal antibody on eosinophils, airway hyperresponsiveness, and the late asthmatic response. Lancet356, 2144–2148 (2000). CASPubMed Google Scholar
Food-Page, P. et al. A study to evaluate safety and efficacy of mepolizumab in patients with moderate persistent asthma. Am. J. Respir. Crit. Care Med.176, 1062–1071 (2007). Google Scholar
Haldar, P. et al. Mepolizumab and exacerbations of refractory eosinophilic asthma. N. Engl. J. Med.360, 973–984 (2009). CASPubMedPubMed Central Google Scholar
Nair, P. et al. Mepolizumab for prednisone-dependent asthma with sputum eosinophilia. N. Engl. J. Med.360, 985–993 (2009). These two studies demonstrated for the first time that the IL-5-targeted monoclonal antibody mepolizumab can decrease the frequency of asthma exacerbations and corticosteroid use in small selected groups of patients with severe eosinophilic steroid-dependent asthma, who were recruited to the study on the basis of having high eosinophil levels in induced sputum. CASPubMed Google Scholar
Pavord, I. D. et al. Mepolizumab for severe eosinophilic asthma (DREAM): a multicentre, double-blind, placebo-controlled trial. Lancet380, 651–659 (2012). This large clinical study showed that mepolizumab decreased the frequency of asthma exacerbations, even at low doses, in a large number of patients with severe asthma who had sputum and blood eosinophilia as well as elevated levels of easily measurable exhaled nitric oxide. CASPubMed Google Scholar
Castro, M. et al. Reslizumab for poorly controlled, eosinophilic asthma: a randomized, placebo-controlled study. Am. J. Respir. Crit. Care Med.184, 1125–1132 (2011). CASPubMed Google Scholar
Busse, W. W. et al. Safety profile, pharmacokinetics and biologic activity of MEDI-563, an anti-IL-5 receptor α antibody, in a phase I study of subjects with mild asthma. J. Allergy Clin. Immunol.125, 1237–1244 (2010). CASPubMed Google Scholar
Ghazi, A., Trikha, A. & Calhoun, W. J. Benralizumab — a humanized mAb to IL-5Rα with enhanced antibody-dependent cell-mediated cytotoxicity — a novel approach for the treatment of asthma. Expert Opin. Biol. Ther.12, 113–118 (2012). CASPubMed Google Scholar
Zhou, C. Y., Crocker, I. C., Koenig, G., Romero, F. A. & Townley, R. G. Anti-interleukin-4 inhibits immunoglobulin E production in a murine model of atopic asthma. J. Asthma34, 195–201 (1997). CASPubMed Google Scholar
Corry, D. B. et al. Interleukin-4, but not interleukin-5 or eosinophils, is required in a murine model of acute airway hyperreactivity. J. Exp. Med.183, 109–117 (1996). CASPubMed Google Scholar
Hart, T. K. et al. Preclinical efficacy and safety of pascolizumab (SB 240683): a humanized anti-interleukin-4 antibody with therapeutic potential in asthma. Clin. Exp. Immunol.130, 93–100 (2002). CASPubMedPubMed Central Google Scholar
Shames, R. S. et al. The safety and pharmacokinetics of SB240683 (anti-interleukin-4 humanized monoclonal antibody) in patients with mild to moderate asthma. J. Allergy Clin. Immunol.163, A523 (2001). Google Scholar
Henderson, W. R. Jr., Chi, E. Y. & Maliszewski, W. J. Soluble IL-4 receptor inhibits airway inflammation following allergen challenge in a mouse model of asthma. J. Immunol.164, 1086–1095 (2000). CASPubMed Google Scholar
Borish, L. C. et al. IL-4 receptor in moderate atopic asthma. A phase I/II randomized, placebo-controlled trial. Am. J. Respir. Crit. Care Med.160, 1816–1823 (1999). CASPubMed Google Scholar
Borish, L. C. et al. IL-4R Asthma Study Group. Efficacy of soluble IL-4 receptor for the treatment of adults with asthma. J. Allergy Clin. Immunol.107, 963–970 (2001). CASPubMed Google Scholar
Steinke, J. W. Anti-interleukin-4 therapy. Immunol. Allergy Clin. North Am.24, 599–614 (2004). PubMed Google Scholar
Blanchet, M. R., Gold, M. J. & McNagny, K. M. Mouse models to evaluate the function of genes associated with allergic airway disease. Curr. Opin. Allergy Clin. Immunol.12, 467–474 (2012). CASPubMed Google Scholar
Reddy, A. T., Lakshmi, S. P. & Reddy, R. C. Murine model of allergen induced asthma. J. Vis. Exp.63, e3771 (2012). Google Scholar
Tomkinson, A. et al. A murine IL-4 receptor antagonist that inhibits IL-4- and IL-13-induced responses prevents antigen-induced airway eosinophilia and airway hyperresponsiveness. J. Immunol.166, 5792–5800 (2001). CASPubMed Google Scholar
Tomkinson, A. et al. Inhaled versus subcutaneous effects of a dual IL-4/IL-13 antagonist in a monkey model of asthma. Allergy65, 69–77 (2010). CASPubMed Google Scholar
Burmeister Getz, E., Fisher, D. M. & Fuller, R. Human pharmacokinetics/pharmacodynamics of an interleukin-4 and interleukin-13 dual antagonist in asthma. J. Clin. Pharmacol.49, 1025–1036 (2009). PubMed Google Scholar
Wenzel, S. et al. Effect of an interleukin-4 variant on late phase asthmatic response to allergen challenge in asthmatic patients: results of two phase 2a studies. Lancet370, 1422–1431 (2007). CASPubMed Google Scholar
Wenzel, S. E. et al. Inhaled pitrakinra, an IL-4/IL-13 antagonist, reduced exacerbations in patients with eosinophilic asthma. Eur. Respir. J.36, P3980 (2010). Google Scholar
Slager, R. E. et al. IL-4 receptor polymorphisms predict reduction in asthma exacerbations during response to an anti-IL-4 receptor α antagonist. J. Allergy Clin. Immunol.130, 516–522 (2012). This is the first large pharmacogenetic analysis showing that a therapeutic asthma strategy based on IL-4 and IL-13 antagonism can be effective in lowering the frequency of asthma exacerbations in selected patients who have specific polymorphisms in the gene encoding the α-chain of the IL-4 receptor. CASPubMedPubMed Central Google Scholar
Perkins, C., Wills-Karp, M. & Finkelman, F. D. IL-4 induces IL-13-independent allergic airway inflammation. J. Allergy Clin. Immunol.118, 410–419 (2006). CASPubMed Google Scholar
Maes, T., Joos, G. F. & Brusselle, G. G. Targeting interleukin-4 in asthma: lost in translation? Am. J. Respir. Cell. Mol. Biol.47, 261–270 (2012). CASPubMed Google Scholar
Kakkar, T. et al. Population PK and IgE pharmacodynamic analysis of a fully human monoclonal antibody against IL-4 receptor. Pharm. Res.28, 2530–2542 (2011). CASPubMed Google Scholar
Corren, J. et al. A randomized, controlled, phase 2 study of AMG 317, an IL-4Rα antagonist. Am. J. Respir. Crit. Care Med.181, 788–796 (2010). CASPubMed Google Scholar
McCusker, C. T. et al. Inhibition of experimental allergic airways disease by local application of a cell-penetrating dominant-negative STAT6 peptide. J. Immunol.179, 2556–2564 (2007). CASPubMed Google Scholar
Chiba, Y., Todoroki, M., Nishida, Y., Tanabe, M. & Misawa, M. A novel STAT6 inhibitor AS1517499 ameliorates antigen-induced bronchial hypercontractility in mice. Am. J. Respir. Cell. Mol. Biol.41, 516–524 (2009). CASPubMed Google Scholar
Wills-Karp, M. Interleukin-13 in asthma pathogenesis. Immunol. Rev.202, 175–190 (2004). CASPubMed Google Scholar
Yang, G. et al. Anti-IL-13 monoclonal antibody inhibits airway hyperresponsiveness, inflammation and airway remodeling. Cytokine28, 224–232 (2004). CASPubMed Google Scholar
Blanchard, C. et al. Inhibition of human interleukin-13-induced respiratory and oesophageal inflammation by anti-human interleukin-13 antibody (CAT-354). Clin. Exp. Allergy35, 1096–1103 (2005). CASPubMed Google Scholar
Singh, D. et al. A phase 1 study evaluating the pharmacokinetics, safety and tolerability of repeat dosing with a human IL-13 antibody (CAT-354) in subjects with asthma. BMC Pulm. Med.10, 3 (2010). PubMedPubMed Central Google Scholar
Gauvreau, G. M. et al. Effects of interleukin-13 blockade on allergen-induced airway responses in mild atopic asthma. Am. J. Respir. Crit. Care Med.183, 1007–1014 (2011). CASPubMed Google Scholar
Cheng, G. et al. Anti-interleukin-9 antibody treatment inhibits airway inflammation and hyperreactivity in mouse asthma model. Am. J. Respir. Crit. Care Med.166, 409–416 (2002). PubMed Google Scholar
White, B., Leon, F., White, W. & Robbie, G. Two first-in-human, open-label, phase I dose-escalation safety trials of MEDI-528, a monoclonal antibody against interleukin-9, in healthy volunteers. Clin. Ther.31, 728–740 (2009). CASPubMed Google Scholar
Parker, J. M. et al. Safety profile and clinical activity of multiple subcutaneous doses of MEDI-528, a humanized anti-interleukin-9 monoclonal antibody, in two randomized phase 2a studies in subjects with asthma. BMC Pulm. Med.11, 14 (2011). CASPubMedPubMed Central Google Scholar
Yamashita, N. et al. Attenuation of airway hyperresponsiveness in a murine asthma model by neutralization of granulocyte-macrophage colony stimulating factor (GM-CSF). Cell. Immunol.219, 92–97 (2002). CASPubMed Google Scholar
Krinner, E. M. et al. A human monoclonal IgG1 potently neutralizing the pro-inflammatory cytokine GM-CSF. Mol. Immunol.44, 916–925 (2007). CASPubMed Google Scholar
Lukacs, N. W. et al. TNF-α mediates recruitment of neutrophils and eosinophils during airway inflammation. J. Immunol.154, S411–S417 (1995). Google Scholar
Howarth, P. H. et al. Tumour necrosis factor-α (TNF-α) as a novel therapeutic target in symptomatic corticosteroid dependent asthma. Thorax60, 1012–1018 (2005). CASPubMedPubMed Central Google Scholar
Berry, M. A. et al. Evidence of a role of tumor necrosis factor-α in refractory asthma. N. Engl. J. Med.354, 697–708 (2006). CASPubMed Google Scholar
Holgate, S. T. et al. Efficacy and safety of etanercept in moderate-to-severe asthma: a randomised, controlled trial. Eur. Respir. J.37, 1352–1359 (2011). CASPubMed Google Scholar
Erin, E. M. et al. The effects of a monoclonal antibody directed against tumor necrosis factor-α in asthma. Am. J. Respir. Crit. Care Med.174, 753–762 (2006). CASPubMed Google Scholar
Wenzel, S. E. et al. A randomized, double-blind, placebo-controlled study of tumor necrosis factor-α blockade in severe persistent asthma. Am. J. Respir. Crit. Care Med.179, 549–558 (2009). This paper reports the results of a large clinical trial in patients with severe persistent asthma, which showed that the TNFα-targeted monoclonal antibody golimumab has an unfavourable risk-benefit profile, suggesting that such a therapeutic strategy may not be suitable for all patients with severe asthma. CASPubMed Google Scholar
Hellings, P. W. et al. Interleukin-17 orchestrates the granulocyte influx into airways after allergen inhalation in a mouse model of allergic asthma. Am. J. Respir. Cell. Mol. Biol.28, 42–50 (2003). CASPubMed Google Scholar
Wakashing, H. et al. IL-23 and Th17 cells enhance Th2-cell-mediated eosinophilic airway inflammation in mice. Am. J. Respir. Crit. Care Med.178, 1023–1032 (2008). Google Scholar
Li, Y. et al. Silencing IL-23 expression by a small hairpin RNA protects against asthma in mice. Exp. Mol. Med.43, 197–204 (2011). PubMedPubMed Central Google Scholar
Park, S. J. & Lee, Y. C. Interleukin-17 regulation: an attractive therapeutic approach for asthma. Respir. Res.11, 78 (2010). PubMedPubMed Central Google Scholar
Tamachi, T. et al. IL-25 enhances allergic airway inflammation by amplifying a TH2 cell-dependent pathway in mice. J. Allergy Clin. Immunol.118, 606–614 (2006). CASPubMed Google Scholar
Kearley, J., Buckland, K. F., Mathie, S. A. & Lloyd, C. M. Resolution of allergic inflammation and airway hyperreactivity is dependent upon disruption of the T1/ST2-IL-33 pathway. Am. J. Respir. Crit. Care Med.179, 772–781 (2009). CASPubMedPubMed Central Google Scholar
Fujita, J. et al. Interleukin-33 induces interleukin-17F in bronchial epithelial cells. Allergy67, 744–750 (2012). This very interesting study, in human bronchial epithelial cells, showed that mouse antibodies directed against the ST2 receptor of the innate cytokine IL-33 are able to inhibit IL-33-induced expression of IL-17F. Therefore, these findings suggest that the IL-33–IL-17F axis is involved in allergic airway inflammation and can be considered as a novel therapeutic target. CASPubMed Google Scholar
Shi, L. et al. Local blockade of TSLP receptor alleviated allergic disease by regulating airway dendritic cells. Clin. Immunol.129, 202–210 (2008). CASPubMed Google Scholar
Li, J. J. et al. IL-27/IFN-γ induce MyD88-dependent steroid-resistant airway hyperresponsiveness by inhibiting glucocorticoid signaling in macrophages. J. Immunol.185, 4401–4409 (2010). CASPubMed Google Scholar
Masuda, E. S. & Schmitz, J. Syk inhibitors as treatment for allergic rhinitis. Pulm. Pharmacol. Ther.21, 461–467 (2008). CASPubMed Google Scholar
Stenton, G. R. et al. Inhibition of allergic inflammation in the airways using aerosolized antisense to Syk kinase. J. Immunol.169, 1028–1036 (2002). CASPubMed Google Scholar
Meltzer, E. O., Berkowitz, R. B. & Grossbard, E. B. An intranasal Syk-kinase inhibitor (R112) improves the symptoms of seasonal allergic rhinitis in a park environment. J. Allergy Clin. Immunol.115, 791–796 (2005). CASPubMed Google Scholar
Massanari, M. et al. Effect of omalizumab on peripheral blood eosinophilia in allergic asthma. Respir. Med.104, 188–196 (2010). CASPubMed Google Scholar
Terracciano, R. et al. Peptidome profiling of induced sputum by mesoporous silica beads and MALDI-TOF MS for non-invasive biomarker discovery of chronic inflammatory lung diseases. Proteomics11, 3402–3414 (2011). CASPubMed Google Scholar
von Mutius, E. & Drazen, J. M. Choosing asthma step-up care. N. Engl. J. Med.362, 1042–1043 (2010). CASPubMed Google Scholar
Busse, W. et al. Omalizumab, anti-IgE recombinant humanized monoclonal antibody for the treatment of severe allergic asthma. J. Allergy Clin. Immunol.108, 184–190 (2001). CASPubMed Google Scholar
Solér, M. et al. The anti-IgE antibody omalizumab reduces exacerbations and steroid requirement in allergic asthmatics. Eur. Respir. J.18, 254–261 (2001). PubMed Google Scholar
Holgate, S. T. et al. Efficacy and tolerability of a recombinant anti-immunoglobulin E antibody (omalizumab) in severe allergic asthma. Clin. Exp. Allergy34, 632–638 (2004). CASPubMed Google Scholar
Vignola, A. M. et al. Efficacy and tolerability of anti-immunoglobulin E therapy with omalizumab in patients with concomitant allergic asthma and persistent allergic rhinitis: SOLAR. Allergy59, 709–717 (2004). CASPubMed Google Scholar
Ayres, J. G. et al. Efficacy and tolerability of anti-immunoglobulin E therapy with omalizumab in patients with poorly controlled (moderate-to-severe) allergic asthma. Allergy59, 701–708 (2004). CASPubMed Google Scholar
Humbert, M. et al. Benefits of omalizumab as add-on therapy in patients with severe persistent asthma who are inadequately controlled despite best available therapy (GINA 2002 step 4 treatment): INNOVATE. Allergy60, 309–316 (2005). This is one of the most important pre-marketing trials showing that an add-on treatment with omalizumab improves the control of inadequately controlled allergic asthma, thus reducing the occurrence of disease exacerbations, emergency hospital visits and hospitalizations. CASPubMed Google Scholar
Pelaia, G. et al. Omalizumab decreases exacerbation frequency, oral intake of corticosteroids and peripheral blood eosinophils in atopic patients with uncontrolled asthma. Int. J. Clin. Pharmacol. Ther.49, 713–721 (2011). CASPubMed Google Scholar
Molimard, M. de Blay, F., Didier, A. & Le Gros, V. Effectiveness of omalizumab (Xolair) in the first patients treated in real-life practice in France. Respir. Med.102, 71–76 (2008). PubMed Google Scholar
Cazzola, M. et al. Italian real-life experience of omalizumab. Respir. Med.104, 1410–1416 (2010). This is a post-marketing study that, in addition to corroborating the findings of pre-marketing clinical trials, highlights the ability of omalizumab to reduce the use of other asthma drugs such as corticosteroids, leukotriene inhibitors and theophylline. CASPubMed Google Scholar
Miller, C. W. T., Krishnaswamy, N., Johnston, C. & Krishnaswamy, G. Severe asthma and the omalizumab option. Clin. Mol. Allergy6, 4 (2008). PubMedPubMed Central Google Scholar
Busse, W. et al. Omalizumab and the risk of malignancy: results from a pooled analysis. J. Allergy Clin. Immunol.129, 983–989 (2012). CASPubMed Google Scholar
Cox, L. et al. American Academy of Allergy, Asthma & Immunology/American College of Allergy, Asthma and Immunology Joint Task Force report on omalizumab-associated anaphylaxis. J. Allergy Clin. Immunol.120, 1373–1377 (2007). CASPubMed Google Scholar
US Food and Drug Adminisration (FDA). Early communication about an ongoing safety review of omalizumab (marketed as Xolair). FDA website[online], (2009).