Treatment of severe asthma: entering the era of targeted therapy

References

• Global Initiative for Asthma (GINA). Global strategy for asthma management and prevention. Revised 2014 http://www.ginasthma.org/local/uploads/files/GINA_Report_2014_Aug12.pdf 2014
   Google Scholar
• Alvarez-Puebla MJ, Olaguibel Rivera JM, Almudevar E, et al. Cutoff point for exhaled nitric oxide corresponding to 3% sputum eosinophils. J Investig Allergol Clin Immunol 2015;25:107-11
   PubMed Web of Science ®Google Scholar
• Lotvall J, Akdis CA, Bacharier LB, et al. Asthma endotypes: a new approach to classification of disease entities within the asthma syndrome. J Allergy Clin Immunol 2011;127:355-60
   PubMed Web of Science ®Google Scholar
• Fajt ML, Wenzel SE. Asthma phenotypes and the use of biologic medications in asthma and allergic disease: the next steps toward personalized care. J Allergy Clin Immunol 2015;135:299-310
   PubMed Web of Science ®Google Scholar
• Wenzel SE. Asthma phenotypes: the evolution from clinical to molecular approaches. Nat Med 2012;18:716-25
   PubMed Web of Science ®Google Scholar
• Trejo Bittar HE, Yousem SA, Wenzel SE. Pathobiology of severe asthma. Annu Rev Pathol 2015;10:511-45
   PubMed Web of Science ®Google Scholar
• Lambrecht BN, Hammad H. The immunology of asthma. Nat Immunol 2015;16:45-56
   PubMed Web of Science ®Google Scholar
• Tan DJ, Walters EH, Perret JL, et al. Age-of-asthma onset as a determinant of different asthma phenotypes in adults: a systematic review and meta-analysis of the literature. Expert Rev Respir Med 2015;9:109-23
   PubMed Web of Science ®Google Scholar
• Chung KF. Asthma phenotyping: a necessity for improved therapeutic precision and new targeted therapies. J Intern Med 2015. [Epub ahead of print]
   PubMedGoogle Scholar
• Rayees S, Malik F, Bukhari SI, Singh G. Linking GATA-3 and interleukin-13: implications in asthma. Inflamm Res 2014;63:255-65
   PubMed Web of Science ®Google Scholar
• Krug N, Hohlfeld JM, Kirsten AM, et al. Allergen-induced asthmatic responses modified by a GATA3-specific DNAzyme. N Engl J Med 2015;372:1987-95
   PubMed Web of Science ®Google Scholar
• Gour N, Wills-Karp M. IL-4 and IL-13 signaling in allergic airway disease. Cytokine 2015;75(1):68-78
   PubMed Web of Science ®Google Scholar
• Zhao P, Xiao X, Ghobrial RM, Li XC. IL-9 and Th9 cells: progress and challenges. Int Immunol 2013;25:547-51
   PubMed Web of Science ®Google Scholar
• Ingram JL, Kraft M. IL-13 in asthma and allergic disease: asthma phenotypes and targeted therapies. J Allergy Clin Immunol 2012;130:829-42
   PubMed Web of Science ®Google Scholar
• Zimmermann N, Hershey GK, Foster PS, Rothenberg ME. Chemokines in asthma: cooperative interaction between chemokines and IL-13. J Allergy Clin Immunol 2003;111:227-42
   PubMed Web of Science ®Google Scholar
• Fajt ML, Wenzel SE. Asthma phenotypes and the use of biologic medications in asthma and allergic disease: the next steps toward personalized care. J Allergy Clin Immunol 2015;135:299-310
   PubMed Web of Science ®Google Scholar
• Brown HM. Treatment of chronic asthma with prednisolone; significance of eosinophils in the sputum. Lancet 1958;2:1245-7
   PubMed Web of Science ®Google Scholar
• Jia G, Erickson RW, Choy DF, et al. Periostin is a systemic biomarker of eosinophilic airway inflammation in asthmatic patients. J Allergy Clin Immunol 2012;130:647-54
   PubMed Web of Science ®Google Scholar
• Munoz X, Bustamante V, Lopez-Campos JL, et al. Usefulness of noninvasive methods for the study of bronchial inflammation in the control of patients with asthma. Int Arch Allergy Immunol 2015;166:1-12
   PubMed Web of Science ®Google Scholar
• Dweik RA, Boggs PB, Erzurum SC, et al. An official ATS clinical practice guideline: interpretation of exhaled nitric oxide levels (FENO) for clinical applications. Am J Respir Crit Care Med 2011;184:602-15
   PubMed Web of Science ®Google Scholar
• Matsumoto H. Serum periostin: a novel biomarker for asthma management. Allergol Int 2014;63:153-60
   PubMed Web of Science ®Google Scholar
• Agarwal R. Severe asthma with fungal sensitization. Curr Allergy Asthma Rep 2011;11:403-13
   PubMed Web of Science ®Google Scholar
• McKenzie AN, Spits H, Eberl G. Innate lymphoid cells in inflammation and immunity. Immunity 2014;41:366-74
   PubMed Web of Science ®Google Scholar
• Brusselle GG, Maes T, Bracke KR. Eosinophils in the spotlight: Eosinophilic airway inflammation in nonallergic asthma. Nat Med 2013;19:977-9
   PubMed Web of Science ®Google Scholar
• Desai D, Newby C, Symon FA, et al. Elevated sputum interleukin-5 and submucosal eosinophilia in obese individuals with severe asthma. Am J Respir Crit Care Med 2013;188:657-63
   PubMed Web of Science ®Google Scholar
• van Huisstede A, Rudolphus A, van Schadewijk A, et al. Bronchial and systemic inflammation in morbidly obese subjects with asthma: a biopsy study. Am J Respir Crit Care Med 2014;190:951-4
   PubMed Web of Science ®Google Scholar
• Al-Alwan A, Bates JH, Chapman DG, et al. The nonallergic asthma of obesity. A matter of distal lung compliance. Am J Respir Crit Care Med 2014;189:1494-502
   PubMed Web of Science ®Google Scholar
• van Huisstede A, Rudolphus A, Castro CM, et al. Effect of bariatric surgery on asthma control, lung function and bronchial and systemic inflammation in morbidly obese subjects with asthma. Thorax 2015;70:659-67
   PubMed Web of Science ®Google Scholar
• Moore WC, Meyers DA, Wenzel SE, et al. Identification of asthma phenotypes using cluster analysis in the Severe Asthma Research Program. Am J Respir Crit Care Med 2010;181:315-23
   PubMed Web of Science ®Google Scholar
• Louie S, Zeki AA, Schivo M, et al. The asthma-chronic obstructive pulmonary disease overlap syndrome: pharmacotherapeutic considerations. Expert Rev Clin Pharmacol 2013;6:197-219
   PubMed Web of Science ®Google Scholar
• Kew KM, Karner C, Mindus SM, Ferrara G. Combination formoterol and budesonide as maintenance and reliever therapy versus combination inhaler maintenance for chronic asthma in adults and children. Cochrane Database Syst Rev 2013;12:CD009019
   Google Scholar
• Kerstjens HA, Engel M, Dahl R, et al. Tiotropium in asthma poorly controlled with standard combination therapy. N Engl J Med 2012;367:1198-207
   PubMed Web of Science ®Google Scholar
• Peters SP, Bleecker ER, Kunselman SJ, et al. Predictors of response to tiotropium versus salmeterol in asthmatic adults. J Allergy Clin Immunol 2013;132:1068-74
   PubMed Web of Science ®Google Scholar
• Kerstjens HA, Casale TB, Bleecker ER, et al. Tiotropium or salmeterol as add-on therapy to inhaled corticosteroids for patients with moderate symptomatic asthma: two replicate, double-blind, placebo-controlled, parallel-group, active-comparator, randomised trials. Lancet Respir Med 2015;3(5):367-76
   PubMed Web of Science ®Google Scholar
• Chung KF, Wenzel SE, Brozek JL, et al. International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma. Eur Respir J 2014;43:343-73
   PubMed Web of Science ®Google Scholar
• Korn S, Both J, Jung M, et al. Prospective evaluation of current asthma control using ACQ and ACT compared with GINA criteria. Ann Allergy Asthma Immunol 2011;107:474-9
   PubMed Web of Science ®Google Scholar
• Hekking PP, Wener RR, Amelink M, et al. The prevalence of severe refractory asthma. J Allergy Clin Immunol 2015;135:896-902
   PubMed Web of Science ®Google Scholar
• Sullivan SD, Rasouliyan L, Russo PA, et al. Extent, patterns, and burden of uncontrolled disease in severe or difficult-to-treat asthma. Allergy 2007;62:126-33
   PubMed Web of Science ®Google Scholar
• Bel EH, Sousa A, Fleming L, et al. Diagnosis and definition of severe refractory asthma: an international consensus statement from the Innovative Medicine Initiative (IMI). Thorax 2011;66:910-17
   PubMed Web of Science ®Google Scholar
• Schleich F, Brusselle G, Louis R, et al. Heterogeneity of phenotypes in severe asthmatics. The Belgian Severe Asthma Registry (BSAR). Respir Med 2014;108:1723-32
   PubMed Web of Science ®Google Scholar
• Schatz M, Hsu JW, Zeiger RS, et al. Phenotypes determined by cluster analysis in severe or difficult-to-treat asthma. J Allergy Clin Immunol 2014;133:1549-56
   PubMed Web of Science ®Google Scholar
• Bobolea I, Barranco P, Del PV, et al. Sputum periostin in patients with different severe asthma phenotypes. Allergy 2015;70:540-6
   PubMed Web of Science ®Google Scholar
• Haldar P, Pavord ID, Shaw DE, et al. Cluster analysis and clinical asthma phenotypes. Am J Respir Crit Care Med 2008;178:218-24
   PubMed Web of Science ®Google Scholar
• Nicolini G, Cremonesi G, Melani AS. Inhaled corticosteroid therapy with nebulized beclometasone dipropionate. Pulm Pharmacol Ther 2010;23:145-55
   PubMed Web of Science ®Google Scholar
• Vogelmeier C, Kardos P, Hofmann T, et al. Nebulised budesonide using a novel device in patients with oral steroid-dependent asthma. Eur Respir J 2015;45:1273-82
   PubMed Web of Science ®Google Scholar
• Dombret MC, Alagha K, Philippe BL, et al. Bronchial thermoplasty: a new therapeutic option for the treatment of severe, uncontrolled asthma in adults. Eur Respir Rev 2014;23:510-18
   PubMedGoogle Scholar
• Manson SC, Brown RE, Cerulli A, Vidaurre CF. The cumulative burden of oral corticosteroid side effects and the economic implications of steroid use. Respir Med 2009;103:975-94
   PubMed Web of Science ®Google Scholar
• Comet R, Domingo C, Larrosa M, et al. Benefits of low weekly doses of methotrexate in steroid-dependent asthmatic patients. A double-blind, randomized, placebo-controlled study. Respir Med 2006;100:411-19
   PubMed Web of Science ®Google Scholar
• Fukuda T, Asakawa J, Motojima S, Makino S. Cyclosporine A reduces T lymphocyte activity and improves airway hyperresponsiveness in corticosteroid-dependent chronic severe asthma. Ann Allergy Asthma Immunol 1995;75:65-72
   PubMed Web of Science ®Google Scholar
• Salmun LM, Barlan I, Wolf HM, et al. Effect of intravenous immunoglobulin on steroid consumption in patients with severe asthma: a double-blind, placebo-controlled, randomized trial. J Allergy Clin Immunol 1999;103:810-15
   PubMed Web of Science ®Google Scholar
• Corrigan CJ. Asthma refractory to glucocorticoids: the role of newer immunosuppressants. Am J Respir Med 2002;1:47-54
   PubMedGoogle Scholar
• Wenzel SE, Barnes PJ, Bleecker ER, et al. A randomized, double-blind, placebo-controlled study of tumor necrosis factor-alpha blockade in severe persistent asthma. Am J Respir Crit Care Med 2009;179:549-58
   PubMed Web of Science ®Google Scholar
• Parnham MJ, Erakovic HV, Giamarellos-Bourboulis EJ, et al. Azithromycin: mechanisms of action and their relevance for clinical applications. Pharmacol Ther 2014;143:225-45
   PubMed Web of Science ®Google Scholar
• Simpson JL, Powell H, Boyle MJ, et al. Clarithromycin targets neutrophilic airway inflammation in refractory asthma. Am J Respir Crit Care Med 2008;177:148-55
   PubMed Web of Science ®Google Scholar
• Sutherland ER, King TS, Icitovic N, et al. A trial of clarithromycin for the treatment of suboptimally controlled asthma. J Allergy Clin Immunol 2010;126:747-53
   PubMed Web of Science ®Google Scholar
• Slater M, Rivett DW, Williams L, et al. The impact of azithromycin therapy on the airway microbiota in asthma. Thorax 2014;69:673-4
   PubMed Web of Science ®Google Scholar
• Uzun S, Djamin RS, Kluytmans JA, et al. Azithromycin maintenance treatment in patients with frequent exacerbations of chronic obstructive pulmonary disease (COLUMBUS): a randomised, double-blind, placebo-controlled trial. Lancet Respir Med 2014;2:361-8
   PubMed Web of Science ®Google Scholar
• Brusselle GG, Vanderstichele C, Jordens P, et al. Azithromycin for prevention of exacerbations in severe asthma (AZISAST): a multicentre randomised double-blind placebo-controlled trial. Thorax 2013;68:322-9
   PubMed Web of Science ®Google Scholar
• Wong EH, Porter JD, Edwards MR, Johnston SL. The role of macrolides in asthma: current evidence and future directions. Lancet Respir Med 2014;2:657-70
   PubMed Web of Science ®Google Scholar
• Normansell R, Walker S, Milan SJ, et al. Omalizumab for asthma in adults and children. Cochrane Database Syst Rev 2014;1:CD003559
   PubMed Web of Science ®Google Scholar
• Lowe PJ, Tannenbaum S, Gautier A, Jimenez P. Relationship between omalizumab pharmacokinetics, IgE pharmacodynamics and symptoms in patients with severe persistent allergic (IgE-mediated) asthma. Br J Clin Pharmacol 2009;68:61-76
   PubMed Web of Science ®Google Scholar
• Korn S, Haasler I, Fliedner F, et al. Monitoring free serum IgE in severe asthma patients treated with omalizumab. Respir Med 2012;106:1494-500
   PubMed Web of Science ®Google Scholar
• Hanania NA, Wenzel S, Rosen K, et al. Exploring the effects of omalizumab in allergic asthma: an analysis of biomarkers in the EXTRA study. Am J Respir Crit Care Med 2013;187:804-11
   PubMed Web of Science ®Google Scholar
• Garcia G, Magnan A, Chiron R, et al. A proof-of-concept, randomized, controlled trial of omalizumab in patients with severe, difficult-to-control, nonatopic asthma. Chest 2013;144:411-19
   PubMed Web of Science ®Google Scholar
• Lommatzsch M, Korn S, Buhl R, Virchow JC. Against all odds: anti-IgE for intrinsic asthma? Thorax 2014;69:94-6
   PubMed Web of Science ®Google Scholar
• Lowe PJ, Renard D. Omalizumab decreases IgE production in patients with allergic (IgE-mediated) asthma; PKPD analysis of a biomarker, total IgE. Br J Clin Pharmacol 2011;72:306-20
   PubMed Web of Science ®Google Scholar
• Busse WW, Trzaskoma B, Omachi TA, et al. Evaluating Xolair Persistency Of Response After Long-Term Therapy (xport). Abstract. Am J Respir Crit Care Med 2014;A6576
   Google Scholar
• Namazy J, Cabana MD, Scheuerle AE, et al. The Xolair Pregnancy Registry (EXPECT): the safety of omalizumab use during pregnancy. J Allergy Clin Immunol 2015;135:407-12
   PubMed Web of Science ®Google Scholar
• British guideline on the management of asthma. Thorax 2014;69(Suppl 1):1-192
   Google Scholar
• Leckie MJ, ten BA, Khan J, et al. Effects of an interleukin-5 blocking monoclonal antibody on eosinophils, airway hyper-responsiveness, and the late asthmatic response. Lancet 2000;356:2144-8
   PubMed Web of Science ®Google Scholar
• Plotz SG, Simon HU, Darsow U, et al. Use of an anti-interleukin-5 antibody in the hypereosinophilic syndrome with eosinophilic dermatitis. N Engl J Med 2003;349:2334-9
   PubMed Web of Science ®Google Scholar
• Rothenberg ME, Klion AD, Roufosse FE, et al. Treatment of patients with the hypereosinophilic syndrome with mepolizumab. N Engl J Med 2008;358:1215-28
   PubMed Web of Science ®Google Scholar
• Haldar P, Brightling CE, Hargadon B, et al. Mepolizumab and exacerbations of refractory eosinophilic asthma. N Engl J Med 2009;360:973-84
   PubMed Web of Science ®Google Scholar
• Nair P, Pizzichini MM, Kjarsgaard M, et al. Mepolizumab for prednisone-dependent asthma with sputum eosinophilia. N Engl J Med 2009;360:985-93
   PubMed Web of Science ®Google Scholar
• Bel EH, Wenzel SE, Thompson PJ, et al. Oral glucocorticoid-sparing effect of mepolizumab in eosinophilic asthma. N Engl J Med 2014;371:1189-97
   PubMed Web of Science ®Google Scholar
• Castro M, Mathur S, Hargreave F, et al. Reslizumab for poorly controlled, eosinophilic asthma: a randomized, placebo-controlled study. Am J Respir Crit Care Med 2011;184:1125-32
   PubMed Web of Science ®Google Scholar
• Castro M, Zangrilli J, Wechsler ME, et al. Reslizumab for inadequately controlled asthma with elevated blood eosinophil counts: results from two multicentre, parallel, double-blind, randomised, placebo-controlled, phase 3 trials. Lancet Respir Med 2015;3(5):355-66
   PubMed Web of Science ®Google Scholar
• Ortega HG, Liu MC, Pavord ID, et al. Mepolizumab treatment in patients with severe eosinophilic asthma. N Engl J Med 2014;371:1198-207
   PubMed Web of Science ®Google Scholar
• Pavord ID, Korn S, Howarth P, et al. Mepolizumab for severe eosinophilic asthma (DREAM): a multicentre, double-blind, placebo-controlled trial. Lancet 2012;380:651-9
   PubMed Web of Science ®Google Scholar
• Haldar P, Brightling CE, Singapuri A, et al. Outcomes after cessation of mepolizumab therapy in severe eosinophilic asthma: a 12-month follow-up analysis. J Allergy Clin Immunol 2014;133:921-3
   PubMed Web of Science ®Google Scholar
• Busse WW, Katial R, Gossage D, et al. Safety profile, pharmacokinetics, and biologic activity of MEDI-563, an anti-IL-5 receptor alpha antibody, in a phase I study of subjects with mild asthma. J Allergy Clin Immunol 2010;125:1237-44
   PubMed Web of Science ®Google Scholar
• Laviolette M, Gossage DL, Gauvreau G, et al. Effects of benralizumab on airway eosinophils in asthmatic patients with sputum eosinophilia. J Allergy Clin Immunol 2013;132:1086-96
   PubMed Web of Science ®Google Scholar
• Castro M, Wenzel SE, Bleecker ER, et al. Benralizumab, an anti-interleukin 5 receptor alpha monoclonal antibody, versus placebo for uncontrolled eosinophilic asthma: a phase 2b randomised dose-ranging study. Lancet Respir Med 2014;2:879-90
   PubMed Web of Science ®Google Scholar
• Nowak RM, Parker JM, Silverman RA, et al. A randomized trial of benralizumab, an antiinterleukin 5 receptor alpha monoclonal antibody, after acute asthma. Am J Emerg Med 2015;33:14-20
   PubMed Web of Science ®Google Scholar
• Gleich GJ, Klion AD, Lee JJ, Weller PF. The consequences of not having eosinophils. Allergy 2013;68:829-35
   PubMed Web of Science ®Google Scholar
• Taube C, Duez C, Cui ZH, et al. The role of IL-13 in established allergic airway disease. J Immunol 2002;169:6482-9
   PubMed Web of Science ®Google Scholar
• Woodruff PG, Boushey HA, Dolganov GM, et al. Genome-wide profiling identifies epithelial cell genes associated with asthma and with treatment response to corticosteroids. Proc Natl Acad Sci USA 2007;104:15858-63
   PubMed Web of Science ®Google Scholar
• McKenzie AN, Fallon PG. Decoy receptors in the regulation of T helper cell type 2 responses. J Exp Med 2003;197:675-9
   PubMed Web of Science ®Google Scholar
• Scheerens H, Arron JR, Zheng Y, et al. The effects of lebrikizumab in patients with mild asthma following whole lung allergen challenge. Clin Exp Allergy 2014;44:38-46
   PubMed Web of Science ®Google Scholar
• Corren J, Lemanske RF, Hanania NA, et al. Lebrikizumab treatment in adults with asthma. N Engl J Med 2011;365:1088-98
   PubMed Web of Science ®Google Scholar
• Piper E, Brightling C, Niven R, et al. A phase II placebo-controlled study of tralokinumab in moderate-to-severe asthma. Eur Respir J 2013;41:330-8
   PubMed Web of Science ®Google Scholar
• Wenzel S, Wilbraham D, Fuller R, 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. Lancet 2007;370:1422-31
   PubMed Web of Science ®Google Scholar
• Slager RE, Otulana BA, Hawkins GA, et al. IL-4 receptor polymorphisms predict reduction in asthma exacerbations during response to an anti-IL-4 receptor alpha antagonist. J Allergy Clin Immunol 2012;130:516-22
   PubMed Web of Science ®Google Scholar
• Wenzel S, Ford L, Pearlman D, et al. Dupilumab in persistent asthma with elevated eosinophil levels. N Engl J Med 2013;368:2455-66
   PubMed Web of Science ®Google Scholar
• Wenzel SE. A6362. Presented at American Thoracic Society International Conference; 15 – 20 May 2015; Denver
   Google Scholar
• Beck LA, Thaci D, Hamilton JD, et al. Dupilumab treatment in adults with moderate-to-severe atopic dermatitis. N Engl J Med 2014;371:130-9
   PubMed Web of Science ®Google Scholar
• Smith SG, Gugilla A, Mukherjee M, et al. Thymic stromal lymphopoietin and IL-33 modulate migration of hematopoietic progenitor cells in patients with allergic asthma. J Allergy Clin Immunol 2015;135(6):1594-602
   PubMed Web of Science ®Google Scholar
• Gauvreau GM, O’Byrne PM, Boulet LP, et al. Effects of an anti-TSLP antibody on allergen-induced asthmatic responses. N Engl J Med 2014;370:2102-10
   PubMed Web of Science ®Google Scholar
• Busse WW, Holgate S, Kerwin E, et al. Randomized, double-blind, placebo-controlled study of brodalumab, a human anti-IL-17 receptor monoclonal antibody, in moderate to severe asthma. Am J Respir Crit Care Med 2013;188:1294-302
   PubMed Web of Science ®Google Scholar
• Li Y, Hua S. Mechanisms of pathogenesis in allergic asthma: role of interleukin-23. Respirology 2014;19:663-9
   PubMed Web of Science ®Google Scholar
• Krueger JG, Ferris LK, Menter A, et al. Anti-IL-23A mAb BI 655066 for treatment of moderate-to-severe psoriasis: Safety, efficacy, pharmacokinetics, and biomarker results of a single-rising-dose, randomized, double-blind, placebo-controlled trial. J Allergy Clin Immunol 2015;136(1):116-24; e7
   PubMed Web of Science ®Google Scholar
• Kopp T, Riedl E, Bangert C, et al. Clinical improvement in psoriasis with specific targeting of interleukin-23. Nature 2015;521:222-6
   PubMed Web of Science ®Google Scholar