Targeting the interleukin-4 and interleukin-13 pathways in severe asthma: Current knowledge and future needs

Current Opinion in Pulmonary Medicine

Volumn 24, Issue 1, 2018, Pages 50-55

  Parulekar, Amit D ^a   Kao, Christina C ^a   DIamant, Zuzana ^b,c   Hanania, Nicola A ^a  

^a BAYLOR COLLEGE OF MEDICINE   (United States)

^b LUND UNIVERSITY HOSPITAL   (Sweden)

^c UNIVERSITY OF GRONINGEN   (Netherlands)

Author keywords

biologics; dupilumab; lebrikizumab; T2 asthma; tralokinumab

Indexed keywords

DUPILUMAB; INDUCIBLE NITRIC OXIDE SYNTHASE; INTERLEUKIN 13; INTERLEUKIN 13 ANTIBODY; INTERLEUKIN 4; INTERLEUKIN 4 RECEPTOR; INTERLEUKIN 4 RECEPTOR ALPHA; LEBRIKIZUMAB; NITRIC OXIDE; TRALOKINUMAB; TRANSCRIPTION FACTOR RUNX2; ANTIASTHMATIC AGENT; BIOLOGICAL MARKER; INTERLEUKIN 13 RECEPTOR;

ASTHMA; CLINICAL PRACTICE; COMPARATIVE STUDY; DISEASE ASSOCIATION; DISEASE EXACERBATION; DISEASE SEVERITY; DRUG EFFICACY; EOSINOPHIL; FORCED EXPIRATORY VOLUME; HUMAN; PHENOTYPE; PROTEIN TARGETING; REVIEW; SIGNAL TRANSDUCTION; ANTAGONISTS AND INHIBITORS; DRUG EFFECT; IMMUNOLOGY; INFLAMMATION; MOLECULARLY TARGETED THERAPY; PATHOPHYSIOLOGY; PERSONALIZED MEDICINE; PHYSIOLOGY; SEVERITY OF ILLNESS INDEX; TH2 CELL;

ANTI-ASTHMATIC AGENTS; ASTHMA; BIOMARKERS; HUMANS; INFLAMMATION; MOLECULAR TARGETED THERAPY; PHENOTYPE; PRECISION MEDICINE; RECEPTORS, INTERLEUKIN-13; RECEPTORS, INTERLEUKIN-4; SEVERITY OF ILLNESS INDEX; SIGNAL TRANSDUCTION; TH2 CELLS;

EID: 85036668790     PISSN: 10705287     EISSN: 15316971     Source Type: Journal    
DOI: 10.1097/MCP.0000000000000436     Document Type: Review

References (48)

1. Chung KF, Wenzel SE, Brozek JL, et al. International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma. Eur Respir J 2014; 43:343-373.
2. Chung KF. Asthma phenotyping: a necessity for improved therapeutic precision and new targeted therapies. J Intern Med 2016; 279:192-204.
3. Wenzel SE. Emergence of biomolecular pathways to define novel asthma phenotypes. Type-2 immunity and beyond. Am J Respir Cell Mol Biol 2016; 55:1-4.
4. Walker C, Bauer W, Braun RK, et al. Activated T cells and cytokines in bronchoalveolar lavages from patients with various lung diseases associated with eosinophilia. Am J Respir Crit Care Med 1994; 150:1038-1048.
5. Humbert M, Durham SR, Ying S, et al. IL-4 and IL-5 mRNA and protein in bronchial biopsies from patients with atopic and nonatopic asthma: evidence against 'intrinsic' asthma being a distinct immunopathologic entity. Am J Respir Crit Care Med 1996; 154:1497-1504.
6. Ying S, Durham SR, Corrigan CJ, et al. Phenotype of cells expressing mRNA for TH2-type (interleukin 4 and interleukin 5) and TH1-type (interleukin 2 and interferon gamma) cytokines in bronchoalveolar lavage and bronchial biopsies from atopic asthmatic and normal control subjects. Am J Respir Cell Mol Biol 1995; 12:477-487.
7. Ying S, Humbert M, Barkans J, et al. Expression of IL-4 and IL-5 mRNA and protein product by CD4+ and CD8+ T cells, eosinophils, and mast cells in bronchial biopsies obtained from atopic and nonatopic (intrinsic) asthmatics. J Immunol 1997; 158:3539-3544.
8. Shahid SK, Kharitonov SA, Wilson NM, et al. Increased interleukin-4 and decreased interferon-gamma in exhaled breath condensate of children with asthma. Am J Respir Crit Care Med 2002; 165:1290-1293.
9. Humbert M, Durham SR, Kimmitt P, et al. Elevated expression of messenger ribonucleic acid encoding IL-13 in the bronchial mucosa of atopic and nonatopic subjects with asthma. J Allergy Clin Immunol 1997; 99:657-665.
10. Kotsimbos TC, Ernst P, Hamid QA. Interleukin-13 and interleukin-4 are coexpressed in atopic asthma. Proc Assoc Am Physicians 1996; 108: 368-373.
11. Komai-Koma M, McKay A, Thomson L, et al. Immuno-regulatory cytokines in asthma: IL-15 and IL-13 in induced sputum. Clin Exp Allergy 2001; 31:1441-1448.
12. Kroegel C, Julius P,Matthys H, et al. Endobronchial secretion of interleukin-13 following local allergen challenge in atopic asthma: relationship to interleukin-4 and eosinophil counts. Eur Respir J 1996; 9:899-904.
13. Batra V, Musani AI, Hastie AT, et al. Bronchoalveolar lavage fluid concentrations of transforming growth factor (TGF)-beta1, TGF-beta2, interleukin (IL)-4 and IL-13 after segmental allergen challenge and their effects on alphasmooth muscle actin and collagen III synthesis by primary human lung fibroblasts. Clin Exp Allergy 2004; 34:437-444.
14. Zangrilli JG, Shaver JR, Cirelli RA, et al. sVCAM-1 levels after segmental antigen challenge correlate with eosinophil influx, IL-4 and IL-5 production, and the late phase response. Am J Respir Crit Care Med 1995; 151:1346-1353.
15. Huang SK, Xiao HQ, Kleine-Tebbe J, et al. IL-13 expression at the sites of allergen challenge in patients with asthma. J Immunol 1995; 155: 2688-2694.
16. Shi HZ, Deng JM, Xu H, et al. Effect of inhaled interleukin-4 on airway hyperreactivity in asthmatics. Am J Respir Crit Care Med 1998; 157: 1818-1821.
17. Gessner A, Mohrs K, Mohrs M. Mast cells, basophils, and eosinophils acquire constitutive IL-4 and IL-13 transcripts during lineage differentiation that are sufficient for rapid cytokine production. J Immunol 2005; 174:1063-1072.
18. KleinJan A. Airway inflammation in asthma: key players beyond the Th2 pathway. Curr Opin Pulm Med 2016; 22:46-52.
19. Gandhi NA, Pirozzi G, Graham NMH. Commonality of the IL-4/IL-13 pathway in atopic diseases. Expert Rev Clin Immunol 2017; 13:425-437.
20. Kelly-Welch AE, Hanson EM, Boothby MR, Keegan AD. Interleukin-4 and interleukin-13 signaling connections maps. Science 2003; 300:1527-1528.
21. Wood N, Whitters MJ, Jacobson BA, et al. Enhanced interleukin (IL)-13 responses in mice lacking IL-13 receptor alpha J Exp Med 2003; 197:703-709.
22. Pernis AB, Rothman PB. JAK-STAT signaling in asthma. J Clin Invest 2002; 109:1279-1283.
23. Pope SM, Brandt EB, Mishra A, et al. IL-13 induces eosinophil recruitment into the lung by an IL-5-And eotaxin-dependent mechanism. J Allergy Clin Immunol 2001; 108:594-601.
24. Saha SK, Berry MA, Parker D, et al. Increased sputum and bronchial biopsy IL-13 expression in severe asthma. J Allergy Clin Immunol 2008; 121:685-691.
25. Gauthier M, Ray A, Wenzel SE. Evolving concepts of asthma. Am J Respir Crit Care Med 2015; 192:660-668.
26. Woodruff PG, Modrek B, Choy DF, et al. T-helper type 2-driven inflammation defines major subphenotypes of asthma. Am J Respir Crit Care Med 2009; 180:388-395.
27. Szefler SJ, Wenzel S, Brown R, et al. Asthma outcomes: biomarkers. J Allergy Clin Immunol 2012; 129:S9-S23.
28. Korevaar DA, Westerhof GA, Wang J, et al. Diagnostic accuracy of minimally invasive markers for detection of airway eosinophilia in asthma: a systematic review and meta-Analysis. Lancet Respir Med 2015; 3:290-300.
29. Chibana K, Trudeau JB, Mustovich AT, et al. IL-13 induced increases in nitrite levels are primarily driven by increases in inducible nitric oxide synthase as compared with effects on arginases in human primary bronchial epithelial cells. Clin Exp Allergy 2008; 38:936-946.
30. Parulekar AD, Atik MA, Hanania NA. Periostin, a novel biomarker of TH2-driven asthma. Curr Opin Pulm Med 2014; 20:60-65.
31. Takayama G, Arima K, Kanaji T, et al. Periostin: a novel component of subepithelial fibrosis of bronchial asthma downstream of IL-4 and IL-13 signals. J Allergy Clin Immunol 2006; 118:98-104.
32. 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; 130:647-654; e610.
33. Nagasaki T, Matsumoto H, Kanemitsu Y, et al. Using exhaled nitric oxide and serum periostin as a composite marker to identify severe/steroid-insensitive asthma. Am J Respir Crit Care Med 2014; 190:1449-1452.
34. Corren J, Lemanske RF, Hanania NA, et al. Lebrikizumab treatment in adults with asthma. N Engl J Med 2011; 365:1088-1098.
35. Hanania NA, Noonan M, Corren J, et al. Lebrikizumab in moderate-to-severe asthma: pooled data from two randomised placebo-controlled studies. Thorax 2015; 70:748-756.
36. Hanania NA, Korenblat P, Chapman KR, et al. Efficacy and safety of lebrikizumab in patients with uncontrolled asthma (LAVOLTA I and LAVOLTA II): replicate, phase 3, randomised, double-blind, placebo-controlled trials. Lancet Respir Med 2016; 4:781-796.
37. 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; 41:330-338.
38. Brightling CE, Chanez P, Leigh R, et al. Efficacy and safety of tralokinumab in patients with severe uncontrolled asthma: a randomised, double-blind, placebo-controlled, phase 2b trial. Lancet Respir Med 2015; 3:692-701.
39. 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; 370:1422-1431.
40. Otulana BA, Wenzel SE, Ind PW, et al. A phase 2B study of inhaled pitrakinra, an IL-4/IL-13 antagonist, successfully identified responder subpopulations of patients with uncontrolled asthma. Am J Respir Crit Care Med 2011; 183:A6179.
41. Wenzel S, Ford L, Pearlman D, et al. Dupilumab in persistent asthma with elevated eosinophil levels. N Engl J Med 2013; 368:2455-2466.
42. Wenzel S, Castro M, Corren J, et al. Dupilumab efficacy and safety in adults with uncontrolled persistent asthma despite use of medium-to-high-dose inhaled corticosteroids plus a long-Acting beta2 agonist: a randomised double-blind placebo-controlled pivotal phase 2b dose-ranging trial. Lancet 2016; 388:31-44.
43. AstraZeneca provides update on STRATOS 1 Phase III trial of tralokinumab in severe, uncontrolled asthma: [Internet]. astrazeneca.com. 2017. [no volume]. Accessed 20 September 2017.
44. 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; 130:516-522; e514.
45. Regeneron and Sanofi announce positive dupilumab topline results from phase 3 trial in controlled persistent asthma: [Internet]. investor.regeneron.-com. 2017. [no volume]. Accessed 20 September 2017.
46. Normansell R,Walker S, Milan SJ, et al. Omalizumab for asthma in adults and children. Cochrane Database Syst Rev 2014; (1):CD003559.
47. Pavord ID, Korn S, Howarth P, et al. Mepolizumab for severe eosinophilic asthma (DREAM): a multicentre, double-blind, placebo-controlled trial. Lancet 2012; 380:651-659.
48. 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; 3:355-366.