期刊论文详细信息
World Allergy Organization Journal
Anti-IL5 therapy for asthma and beyond
Parameswaran Nair1  Roma Sehmi1  Manali Mukherjee1 
[1] St Joseph’s Healthcare & Department of Medicine, Firestone Institute for Respiratory Health, McMaster University, 50 Charlton Avenue East, Hamilton, Ontario L8N 4A6, Canada
关键词: Benralizumab;    Reslizumab;    Mepolizumab;    Chronic obstructive pulmonary disorder (COPD);    Eosinophilic granulamatosis and polyangitis (EGPA);    Chronic bronchitis;    Churg-strauss syndrome;    Hypereosinophilic syndrome (HES);    Eosinophilic asthma;    IL-5;    Eosinophil;   
Others  :  1145470
DOI  :  10.1186/1939-4551-7-32
 received in 2014-07-02, accepted in 2014-09-30,  发布年份 2014
PDF
【 摘 要 】

Airway inflammation is considered to be the primary component contributing to the heterogeneity and severity of airway disorders. Therapeutic efficacies of diverse novel biologics targeting the inflammatory pathways are under investigation. One such target is IL-5, a type-1 cytokine that is central to the initiation and sustenance of eosinophilic airway inflammation. Over the past decade, anti-IL5 molecules have been documented to have mixed therapeutic benefits in asthmatics. Post hoc analyses of the trials reiterate the importance of identifying the IL-5-responsive patient endotypes. In fact, the currently available anti-IL5 treatments are being considered beyond asthma management; especially in clinical complications with an underlying eosinophilic pathobiology such as hypereosinophilic syndrome (HES) and eosinophilic granulomatosis and polyangitis (EGPA). In addition, closer analyses of the available data indicate alternative mechanisms of tissue eosinophilia that remain uncurbed with the current dosage and delivery platform of the anti-IL5 molecules.

【 授权许可】

   
2014 Mukherjee et al.; licensee BioMed Central Ltd.

【 预 览 】
附件列表
Files Size Format View
20150402093656927.pdf 2674KB PDF download
Figure 1. 158KB Image download
【 图 表 】

Figure 1.

【 参考文献 】
  • [1]Nair P: What is an “eosinophilic phenotype” of asthma? J Allergy Clin Immunol 2013, 132(1):81-83.
  • [2]Rothenberg ME, Hogan SP: The Eosinophil. Annu Rev Immunol 2006, 24(1):147-174.
  • [3]Hargreave FE, Leigh R: Induced sputum, eosinophilic bronchitis, and chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1999, 160(supplement_1):S53-S57.
  • [4]Vaglio A, Buzio C, Zwerina J: Eosinophilic granulomatosis with polyangiitis (Churg–Strauss): state of the art. Allergy 2013, 68(3):261-273.
  • [5]Busse WW, Ring J, Huss-Marp J, Kahn J-E: A review of treatment with mepolizumab, an anti–IL-5 mAb, in hypereosinophilic syndromes and asthma. J Allergy Clin Immunol 2010, 125(4):803-813.
  • [6]Gleich GJ: Mechanisms of eosinophil-associated inflammation. J Allergy Clin Immunol 2000, 105(4):651-663.
  • [7]Foster PS, Hogan SP, Ramsay AJ, Matthaei KI, Young IG: Interleukin 5 deficiency abolishes eosinophilia, airways hyperreactivity, and lung damage in a mouse asthma model. J Exp Med 1996, 183(1):195-201.
  • [8]Bousquet J, Chanez P, Lacoste JY, Barnéon G, Ghavanian N, Enander I, Venge P, Ahlstedt S, Simony-Lafontaine J, Godard P, Michel F-B: Eosinophilic inflammation in asthma. New Engl J Med 1990, 323(15):1033-1039.
  • [9]Shi H-Z, Xiao C-Q, Zhong D, Qin S-M, Liu YI, Liang G-R, Xu HUI, Chen Y-Q, Long X-M, Xie Z-F: Effect of inhaled interleukin-5 on airway hyperreactivity and eosinophilia in asthmatics. Am J Respir Crit Care Med 1998, 157(1):204-209.
  • [10]Hambly N, Nair P: Monoclonal antibodies for the treatment of refractory asthma. Curr Opin Pulm Med 2014, 20(1):87-94. doi:10.1097/MCP.0000000000000007
  • [11]Pelaia G, Vatrella A, Maselli R: The potential of biologics for the treatment of asthma. Nat Rev Drug Discov 2012, 11(12):958-972.
  • [12]Garcia G, Taillé C, Laveneziana P, Bourdin A, Chanez P, Humbert M: Anti-interleukin-5 therapy in severe asthma. Eur Respir Rev 2013, 22(129):251-257.
  • [13]Lee JJ, Jacobsen EA, McGarry MP, Schleimer RP, Lee NA: Eosinophils in health and disease: the LIAR hypothesis. Clin Exper Allergy 2010, 40(4):563-575.
  • [14]Gleich GJ, Klion AD, Lee JJ, Weller PF: The consequences of not having eosinophils. Allergy 2013, 68(7):829-835.
  • [15]Arron JR, Scheerens H, Matthews JG: Chapter One - Redefining Approaches to Asthma: Developing Targeted Biologic Therapies. In Advances in Pharmacology. Volume 66. Edited by David RW. Academic Press; 2013::1-49. doi: http://dx.doi.org/10.1016/B978-0-12-404717-4.00001-9 webcite
  • [16]Leckie MJ, Brinke At, Khan J, Diamant Z, O’Connor 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-responsìveness, and the late asthmatic response. Lancet 2000, 356(9248):2144-2148.
  • [17]Büttner C, Lun A, Splettstoesser T, Kunkel G, Renz H: Monoclonal anti-interleukin‒5 treatment suppresses eosinophil but not T‒cell functions. Eur Respir J 2003, 21(5):799-803.
  • [18]Kips JC, O’Connor BJ, Langley SJ, Woodcock A, Kerstjens HAM, Postma DS, Danzig M, Cuss F, Pauwels RA: Effect of SCH55700, a humanized anti-human interleukin-5 antibody, in severe persistent asthma. Am J Respir Crit Care Med 2003, 167(12):1655-1659.
  • [19]Flood-Page PT, Menzies-Gow AN, Kay AB, Robinson DS: Eosinophil’s role remains uncertain as anti–interleukin-5 only partially depletes numbers in asthmatic airway. Am J Respir Crit Care Med 2003, 167(2):199-204.
  • [20]Flood-Page P, Swenson C, Faiferman I, Matthews J, Williams M, Brannick L, Robinson D, Wenzel S, Busse W, Hansel TT, Barnes NC: A study to evaluate safety and efficacy of mepolizumab in patients with moderate persistent asthma. Am J Respir Crit Care Med 2007, 176(11):1062-1071.
  • [21]Nair P, Pizzichini MMM, Kjarsgaard M, Inman MD, Efthimiadis A, Pizzichini E, Hargreave FE, O’Byrne PM: Mepolizumab for prednisone-dependent asthma with sputum eosinophilia. New Engl J Med 2009, 360(10):985-993.
  • [22]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. New Engl J Med 2009, 360(10):973-984.
  • [23]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(9842):651-659.
  • [24]Castro M, Mathur S, Hargreave F, Boulet L-P, Xie F, Young J, Wilkins HJ, Henkel T, Nair P: Reslizumab for poorly controlled, eosinophilic asthma. Am J Respir Crit Care Med 2011, 184(10):1125-1132.
  • [25]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 α antibody, in a phase I study of subjects with mild asthma. J Allergy Clin Immunol 2010, 125(6):1237-1244. e1232
  • [26]Laviolette M, Gossage DL, Gauvreau G, Leigh R, Olivenstein R, Katial R, Busse WW, Wenzel S, Wu Y, Datta V, Kolbeck R, Molfino NA: Effects of benralizumab on airway eosinophils in asthmatic patients with sputum eosinophilia. J Allergy Clin Immunol 2013, 132(5):1086-1096. e1085
  • [27]Mario C, David LG, Christine KW, Yanping W, Deepak BK, Nestor AM, Donald GR: Benralizumab reduces exacerbations and improves lung function in adults with uncontrolled eosinophilic asthma. In B101 Asthma Pathogenesis. American Thoracic Society; 2014:A3699-A3699.
  • [28]Ortega HG, Liu MC, Pavord ID, Brusselle GG, FitzGerald JM, Chetta A, Humbert M, Katz LE, Keene ON, Yancey SW, Chanez P, Investigators M: Mepolizumab treatment in patients with severe eosinophilic asthma. N Engl J Med 2014, 371(13):1198-1207.
  • [29]Bel EH, Wenzel SE, Thompson PJ, Prazma CM, Keene ON, Yancey SW, Ortega HG, Pavord ID, the SI: Oral glucocorticoid-sparing effect of mepolizumab in eosinophilic asthma. N Engl J Med 2014, 371(13):1189-1197.
  • [30]Corren J, Weinstein S, Janka L, O’Brien C, Zangrilli J: A randomized phase 3 study f reslizumab efficacy in relation to blood eosinophil levels in patients with moderate to severe asthma. In European Respiratory Society Annual Congress: 10th September 2014. Munich, Germany: European Respiratory Journal; 2014.
  • [31]Bjermer L, Lemiere C, Maspero J, Ciesielska C, O’Brien C, Zangrilli J: A randomized phase 3 study of the efficacy and safety of reslizumab in subjects with asthma with elevated eosinophils. In European Respiratory Society Annual Congress: 7th September 2014. Munich, Germany: European Respiratory Journal; 2014.
  • [32]Nair P: Anti-interleukin-5 monoclonal antibody to treat severe eosinophilic asthma. N Engl J Med 2014, 371(13):1249-1251.
  • [33]Gevaert P, Bachert C, Holtappels G, Novo CP, Van der Heyden J, Fransen L, Depraetere S, Walter H, van Cauwenberge P, Tavernier J: Enhanced soluble interleukin-5 receptor alpha expression in nasal polyposis. Allergy 2003, 58(5):371-379.
  • [34]Ghazi A, Trikha A, Calhoun WJ: 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 2011, 12(1):113-118.
  • [35]Nair P, Dasgupta A, Brightling CE, Chung KF: How to diagnose and phenotype asthma. Clin Chest Med 2012, 33(3):445-457.
  • [36]Gauvreau GM, Boulet LP, Cockcroft DW, Baatjes A, Cote J, Deschesnes F, Davis B, Strinich T, Howie K, Duong M, Watson RM, Renzi PM, O'Byrne PM: Antisense therapy against CCR3 and the common beta chain attenuates allergen-induced eosinophilic responses. Am J Respir Crit Care Med 2008, 177(9):952-958.
  • [37]Neighbour H, Boulet LP, Lemiere C, Sehmi R, Leigh R, Sousa AR, Martin J, Dallow N, Gilbert J, Allen A, Hall D, Nair P: Safety and efficacy of an oral CCR3 antagonist in patients with asthma and eosinophilic bronchitis: a randomized, placebo-controlled clinical trial. Clin Exper Allergy 2014, 44(4):508-516.
  • [38]Guy GB, Tania M, Ken RB: Eosinophils in the Spotlight: Eosinophilic airway inflammation in nonallergic asthma. Nat Med 2013, 19(8):977-979.
  • [39]Licona-Limon P, Kim LK, Palm NW, Flavell RA: TH2, allergy and group 2 innate lymphoid cells. Nat Immunol 2013, 14(6):536-542.
  • [40]Yu S, Kim HY, Chang Y-J, DeKruyff RH, Umetsu DT: Innate lymphoid cells and asthma. J Allergy Clin Immunol 2014, 133(4):943-950.
  • [41]Walker JA, McKenzie ANJ: Development and function of group 2 innate lymphoid cells. Curr Opin Immunol 2013, 25(2):148-155.
  • [42]Allakhverdi Z, Comeau MR, Jessup HK, Yoon BR, Brewer A, Chartier S, Paquette N, Ziegler SF, Sarfati M, Delespesse G: Thymic stromal lymphopoietin is released by human epithelial cells in response to microbes, trauma, or inflammation and potently activates mast cells. J Exp Med 2007, 204(2):253-258.
  • [43]Moore PE, Church TL, Chism DD, Panettieri RA, Shore SA: IL-13 and IL-4 cause eotaxin release in human airway smooth muscle cells: a role for ERK. Am J Physiol Lung Cell Mol Physiol 2002, 282(4):L847-L853.
  • [44]Matsukura S, Stellato C, Georas SN, Casolaro V, Plitt JR, Miura K, Kurosawa S, Schindler U, Schleimer RP: Interleukin-13 upregulates eotaxin expression in airway epithelial cells by a STAT6-dependent mechanism. Am J Respir Cell Mol Biol 2001, 24(6):755-761.
  • [45]Punia N, Smith S, Thomson JV, Irshad A, Nair P, Sehmi R: Interleukin-4 and interleukin-13 prime migrational responses of haemopoietic progenitor cells to stromal cell-derived factor-1α. Clin Exp Allergy 2012, 42(2):255-264.
  • [46]Roma S, Kayla M, Anam I, Navneet P, Steven GS: Thymic stromal lymphopoietin (TSLP) and IL-33 prime the migrational responses of eosinophil-lineage committed progenitor cells. In A14 Interleukin-33: A Pivotal Mediator for Crosstalk between Innate and Adaptive Inflammatory Responses in the Lung. American Thoracic Society; 2013:A1005-A1005.
  • [47]Hui CC, Asher I, Heroux D, Allakhverdi Z, Delespesse G, Denburg JA: Effects of thymic stromal lymphopoietin on cord blood progenitor cell differentiation and hemopoietic cytokine receptors expression. Allergy Asthma Clin Immunol 2011, 7:A24. BioMed Central Full Text
  • [48]Pavord ID, Brightling CE, Woltmann G, Wardlaw AJ: Non-eosinophilic cor ticosteroid unresponsive asthma. Lancet 1999, 353(9171):2213-2214.
  • [49]Fanat AI, Thomson JV, Radford K, Nair P, Sehmi R: Human airway smooth muscle promotes eosinophil differentiation. Clin Exp Allergy 2009, 39(7):1009-1017.
  • [50]Sehmi R, Thomson JV, Catalli AE: Allergy and the bone marrow: transmigration pathways of hemopoietic progenitor cells from the bone marrow. In Allergy Frontiers: Classification and Pathomechanisms,Part 1. Edited by Pawankar P, Holgate S, Rosenwasser LJ. Japan: Springer; 2009:421-432.
  • [51]Kim YK, Uno M, Hamilos DL, Beck L, Bochner B, Schleimer R, Denburg JA: Immunolocalization of CD34 in nasal polyposis. Effect of topical corticosteroids. Am J Respir Cell Mol Biol 1999, 20(3):388-397.
  • [52]Cameron L, Christodoulopoulos P, Lavigne F, Nakamura Y, Eidelman D, McEuen A, Walls A, Tavernier J, Minshall E, Moqbel R, Hamid Q: Evidence for local eosinophil differentiation within allergic nasal mucosa: inhibition with soluble IL-5 receptor. J Immunol 2000, 164(3):1538-1545.
  • [53]Wenzel S, Ford L, Pearlman D, Spector S, Sher L, Skobieranda F, Wang L, Kirkesseli S, Rocklin R, Bock B, Hamilton J, Ming JE, Radin A, Stahl N, Yancopoulos GD, Graham N, Pirozzi G: Dupilumab in Persistent Asthma with Elevated Eosinophil Levels. New Engl J Med 2013, 368(26):2455-2466.
  • [54]Garrett JK, Jameson SC, Thomson B, Collins MH, Wagoner LE, Freese DK, Beck LA, Boyce JA, Filipovich AH, Villanueva JM, Sutton SA, Assa'ad AH, Rothenberg ME: Anti–interleukin-5 (mepolizumab) therapy for hypereosinophilic syndromes. J Allergy Clin Immunol 2004, 113(1):115-119.
  • [55]Rothenberg ME, Klion AD, Roufosse FE, Kahn JE, Weller PF, Simon H-U, Schwartz LB, Rosenwasser LJ, Ring J, Griffin EF, Haig AE, Frewer PIH, Parkin JM, Gleich GJ: Treatment of patients with the hypereosinophilic syndrome with mepolizumab. New Engl J Med 2008, 358(12):1215-1228.
  • [56]Roufosse F, de Lavareille A, Schandené L, Cogan E, Georgelas A, Wagner L, Xi L, Raffeld M, Goldman M, Gleich GJ, Klion A: Mepolizumab as a corticosteroid-sparing agent in lymphocytic variant hypereosinophilic syndrome. J Allergy Clin Immunol 2010, 126(4):828-835. e823
  • [57]Kim S, Marigowda G, Oren E, Israel E, Wechsler ME: Mepolizumab as a steroid-sparing treatment option in patients with Churg-Strauss syndrome. J Allergy Clin Immunol 2010, 125(6):1336-1343.
  • [58]Moosig F, Gross WL, Herrmann K, Bremer JP, Hellmich B: Targeting interleukin-5 in refractory and relapsing churg–strauss syndrome. Ann Intern Med 2011, 155(5):341-343.
  • [59]Brightling CE, Bleecker ER, Panettieri RA, Bafadhel M, She D, Ward CK, Xu X, Birrell C, van der Merwe R: Benralizumab for chronic obstructive pulmonary disease and sputum eosinophilia: a randomised, double-blind, placebo-controlled, phase 2a study. Lancet Respir Med 2014. Sept 5 2014, published online
  • [60]Kahn J-E, Grandpeix-Guyodo C, Marroun I, Catherinot E, Mellot F, Roufosse F, Blétry O: Sustained response to mepolizumab in refractory Churg-Strauss syndrome. J Allergy Clin Immunol 2010, 125(1):267-270.
  • [61]Akuthota P, Weller PF: Eosinophilic pneumonias. Clin Microbiol Rev 2012, 25(4):649-660.
  • [62]Dasgupta A, Neighbour H, Nair P: Targeted therapy of bronchitis in obstructive airway diseases. Pharmacol Ther 2013, 140(3):213-222.
  • [63]Ortega H, Chupp G, Bardin P, Bourdin A, Garcia G, Hartley B, Yancey S, Humbert M: The role of mepolizumab in atopic and nonatopic severe asthma with persistent eosinophilia. Eur Respir J 2014, 44(1):239-241.
  文献评价指标  
  下载次数:0次 浏览次数:3次