Therapeutic Potential of Targeting Interleukin 5 in Asthma
- Garry M. Walsh
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It is recognised that airway inflammation is key to asthma pathogenesis. Biopharmaceutical approaches have identified new therapies that target key cells and mediators that drive the inflammatory responses in the asthmatic lung. Such an approach resulted in the development of biologics targeted at inhibition of interleukin (IL)-4, IL-5 and IL-13. However, early clinical trials with these biologics in patients with asthma were, for the most part, disappointing even though they were highly effective in animal models of asthma. It is becoming apparent that significant clinical effects with anti-cytokine-based therapies are more likely in carefully selected patient populations that take asthma phenotypes into account. The development of discriminatory biomarkers and genetic profiling may aid identification of such patients with asthma. This review summarises the current evidence, demonstrating the effectiveness or otherwise of the targeting of IL-5 in patients with asthma.
- Anandan C, Nurmatov U, van Schayck OC, Sheikh A. Is the prevalence of asthma declining? Systematic review of epidemiological studies. Allergy. 2010;65:152–67. CrossRef
- Barnes PJ. Pathophysiology of allergic inflammation. Immunol Rev. 2011;242:31–50. CrossRef
- Holgate ST. A look at the pathogenesis of asthma: the need for a change in direction. Discov Med. 2010;9:439–47.
- Pelaia G, Vatrella A, Maselli R. The potential of biologics for the treatment of asthma. Nat Rev Drug Discov. 2012;11:958–72. CrossRef
- Barnes PJ, Adcock IM, Ito K. Histone acetylation and deacetylation: importance in inflammatory lung diseases. Eur Respir J. 2005;25:552–63. CrossRef
- Holtzman MJ. Drug development for asthma. Am J Resp Cell Mol Biol. 2003;29:163–71. CrossRef
- Berger WE. New approaches to managing asthma: a US perspective. Ther Clin Risk Manag. 2008;4:363–79.
- Anderson GP. Endotyping asthma: new insights into key pathogenic mechanisms in a complex, heterogeneous disease. Lancet. 2008;372:1107–19. CrossRef
- Turner S, Paton J, Higgins B, Douglas G. British guidelines on the management of asthma: what’s new for 2011? Thorax. 2011;66:1104–5. CrossRef
- Bousquet J, Chanez P, Lacoste JY, Barneon G, Ghavanian N, Enander I, Venge P, Ahlstedt S, Simony-Lafontaine J, Godard P, et al. Eosinophilic inflammation in asthma. N Engl J Med. 1990;323:1033–9. CrossRef
- Nissim Ben Efraim AH, Levi-Schaffer F. Tissue remodeling and angiogenesis in asthma: the role of the eosinophil. Ther Adv Respir Dis. 2008;2:163–71. CrossRef
- Walsh GM. Advances in the immunobiology of eosinophils and their role in disease. Crit Rev Clin Lab Sci. 1999;36:453–96. CrossRef
- O’Byrne PM. The demise of anti-IL-5 for asthma, or not. Am J Respir Crit Care Med. 2007;176:1059–60. CrossRef
- Corren J. Inhibition of interleukin-5 for the treatment of eosinophilic diseases. Discovery Med. 2012;13:305–12.
- Flood-Page PT, Menzies-Gow AN, Kay AB, Robinson D. Eosinophil’s role remains uncertain as anti-interleukin-5 only partially depletes numbers in asthmatic airway. Am J Respir Crit Care Med. 2003;167:199. CrossRef
- Leckie MJ, ten Brinke A, Khan J, Diamant Z, O’Conner BJ, Walls CM, Mathur AK, Cowley HC, Chung KF, Djukanovic R, Hansel TT, Holgate ST, Sterk PJ, Barnes PJ. Effects of an interleukin-5 blocking monoclonal antibody on eosinophils, airway hyper-responsiveness and the late asthmatic response. Lancet. 2000;356:2144–8. CrossRef
- Flood-Page P, Swenson C, Faiferman I, Matthews J, Williams M, Brannick L, Robinson D, Wenzel S, Busse W, Hansel TT, Barnes NC, International Mepolizumab Study Group. A study to evaluate safety and efficacy of mepolizumab in patients with moderate persistent asthma. Am J Respir Crit Care Med. 2007;176:1062–71. CrossRef
- Walsh GM. Mepolizumab and eosinophil-mediated disease. Curr Med Chem. 2009;16:4774–8. CrossRef
- Haldar P, Brightling CE, Hargadon B, Gupta S, Monteiro W, Sousa A, Marshall RP, Bradding P, Green RH, Wardlaw AJ, Pavord ID. Mepolizumab and exacerbations of refractory eosinophilic asthma. N Engl J Med. 2009;360:973–84. CrossRef
- Nair P, Pizzichini MM, Kjarsgaard M, Inman MD, Efthimiadis A, Pizzichini E, Hargreave FE, O’Byrne PM. Mepolizumab for prednisone-dependent asthma with sputum eosinophilia. N Engl J Med. 2009;360:985–93. CrossRef
- Pavord ID, Korn S, Howarth P, Bleecker ER, Buhl R, Keene ON, Ortega H, Chanez P. Mepolizumab for severe eosinophilic asthma (DREAM): a multicentre, double-blind, placebo-controlled trial. Lancet. 2012;380:651–9. CrossRef
- Cook WJ, Walter LJ, Murgolo NJ, Chou CC, Petro M, Zavodny PJ, Narula SK, Ramanathan L, Trotta PP, Nagabhushan TL. Structure and humanization of a rat monoclonal Fab to human interleukin-5. Protein Eng. 1995;97:623–8.
- Egan RW, Athwal D, Bodmer MW, Carter JM, Chapman RW, Chou CC, Cox MA, Emtage JS, Fernandez X, Genatt N, Indelicato SR, Jenh CH, Kreutner W, Kung TT, Mauser PJ, Minnicozzi M, Murgolo NJ, Narula SK, Petro ME, Schilling A, Sehring S, Stelts D, Stephens S, Taremi SS, Zurcher J. Effect of Sch 55700, a humanized monoclonal antibody to human interleukin-5, on eosinophilic responses and bronchial hyperreactivity. Arzneimittelforschung. 1999;49(9):779–90.
- Walsh GM. Reslizumab, a humanized monoclonal anti-IL-5 antibody for the treatment of eosinophil-mediated inflammatory conditions. Curr Opin Mol Ther. 2009;11:329–36.
- Kips JC, O’Conner BJ, Langley SJ, Woodcock A, Kerstjens HAM, Postma DS, Danzig M, Cuss F, Pauwels RA. Effect of SCH55700, a humanised anti-human interleukin-5 antibody in severe persistent asthma: a pilot study. Am J Resp Crit Care Med. 2003;167:1655–9. CrossRef
- Bateman ND, Shahi A, Feeley KM, Woolford TJ. Activated eosinophils in nasal polyps: a comparison of asthmatic and non-asthmatic patients. Clin Otolaryngol. 2005;30:221–5. CrossRef
- Castro M, Mathur S, Hargreave F, Boulet LP, Xie F, Young J, Wilkins HJ, Henkel T, Nair P, for the Res-5-0010 Study Group. Reslizumab for poorly controlled, eosinophilic asthma: a randomized, placebo-controlled study. Am J Respir Crit Care Med. 2011;184:1125–32. CrossRef
- Wechsler ME, Fulkerson PC, Bochner BS, Gauvreau GM, Gleich GJ, Henkel T, Kolbeck R, Mathur SK, Ortega H, Patel J, Prussin C, Renzi P, Rothenberg ME, Roufosse F, Simon D, Simon HU, Wardlaw A, Weller PF, Klion AD. Novel targeted therapies for eosinophilic disorders. J Allergy Clin Immunol. 2012;130:563–71. CrossRef
- Walsh GM. Profile of reslizumab in eosinophilic disease and its potential in the treatment of poorly controlled eosinophilic asthma. Biologics. 2013;7:7–11.
- Kolbeck R, Kozhich A, Koike M, Peng L, Andersson CK, Damschroder MM, Reed JL, Woods R, Dall’acqua WW, Stephens GL, Erjefalt JS, Bjermer L, Humbles AA, Gossage D, Wu H, Kiener PA, Spitalny GL, Mackay CR, Molfino NA, Coyle AJ. MEDI-563, a humanized anti-IL-5 receptor alpha mAb with enhanced antibody-dependent cell-mediated cytotoxicity function. J Allergy Clin Immunol. 2010;125:1344–53. CrossRef
- Walsh GM. Eosinophil apoptosis and clearance in asthma. J Cell Death. 2013;6:17–25. CrossRef
- Busse WW, Katial R, Gossage D, Sari S, Wang B, Kolbeck R, Coyle AJ, Koike M, Spitalny GL, Kiener PA, Geba GP, Molfino NA. Safety profile, pharmacokinetics, and biologic activity of MEDI-563, an anti-IL-5 receptor antibody, in a phase I study of subjects with mild asthma. J Allergy Clin Immunol. 2010;125:1237–44. CrossRef
- Robinson DS. Mepolizumab for severe eosinophilic asthma. Expert Rev Respir Med. 2013;7:13–7. CrossRef
- Holgate ST. Innate and adaptive immune responses in asthma. Nat Med. 2012;18:673–83. CrossRef
- Therapeutic Potential of Targeting Interleukin 5 in Asthma
Volume 27, Issue 6 , pp 559-563
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- Garry M. Walsh (1)
- Author Affiliations
- 1. Section of Immunology and Infection, Division of Applied Medicine, School of Medicine and Dentistry, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen, AB25 2ZD, Scotland, UK