Biologic and Emerging Therapies for Allergic Disease

  • Christina G. Kwong
  • Jeffrey R. StokesEmail author
Living reference work entry


Biologic therapies can be used to treat allergic diseases, which is when the body overreacts or inappropriately responds to normally harmless substances. Several biologic therapies have been successfully developed to treat severe and recalcitrant allergic diseases. Currently approved biologics for the treatment of allergic diseases are omalizumab, benralizumab, mepolizumab, reslizumab, and dupilumab. The majority of these approved biologics are for asthma, but treatment for chronic idiopathic urticaria and atopic dermatitis is also available. Additional research is ongoing for the use of other biologic therapies in a variety of allergic disorders. Approved and investigational biologic therapies for allergic diseases are reviewed in this chapter.


Asthma Allergic disease Omalizumab Mepolizumab Benralizumab Reslizumab Dupilumab 

List of Abbreviations


Chronic idiopathic urticaria


Eczema Area and Severity Index


Proportion of patients who reach 50% improvement as based on the EASI score


Proportion of patients who reach 75% improvement as based on the EASI score


High-affinity IgE receptor


Food and Drug Administration


Fractional exhaled nitric oxide


Forced expiratory volume in 1 second


Inhaled corticosteroid


Investigator’s Global Assessment


Immunoglobulin E




Interleukin-4 receptor


Type 2 innate lymphoid cells


Long-acting beta-adrenoceptor agonist


Leukotriene receptor antagonist

PGD2 receptor

Prostaglandin D2 receptor


Scoring Atopic Dermatitis


T-helper lymphocyte type 2


Thymic stromal lymphopoietin


  1. (2015) FDA approves Nucala to treat severe asthma. In: U.S. Food Drug Adm. Accessed 1 Feb 2018.
  2. (2016) Full Prescribing Information, CINQAIR. In: CINQAIR Website, Teva Respir. LLC. Accessed 15 Nov 2017.
  3. (2016) Full Prescribing Information, ZINBRYTA. In: Zinbryta Website, Biog.Google Scholar
  4. (2017) Full Prescribing Information, DUPIXENT. In: Dupixent Website, Regen. Pharm. Inc. Accessed 10 Dec 2017.
  5. (2017) Full Prescribing Information, FASENRA. In: Fasenra Website, AstraZeneca.Google Scholar
  6. (2017) Full Prescribing Information, NUCALA. In: Nucala Website, GlaxoSmithKline LLC.Google Scholar
  7. (2017) Full Prescribing Information, XOLAIR. In: Xolair Website, Genentech USA, Inc.Google Scholar
  8. Ädelroth E, Rak S, Haahtela T, Aasand G, Rosenhall L, Zetterstrom O, Byrne A, Champain K, Thirlwell J, Della Cioppa G, Sandström T. Recombinant humanized mAb-E25, an anti-IgE mAb, in birch pollen-induced seasonal allergic rhinitis. J Allergy Clin Immunol. 2000;106:253–9.CrossRefGoogle Scholar
  9. Adkinson NF Jr, Bochner BS, Burks AW, Busse WW, Holgate ST, Lemanske RR, O’Hehir RE. Middleton’s allergy principles and practice. 8th ed. Philadelphia: Elsevier/Saunders; 2014.Google Scholar
  10. Alhossan A, Lee CS, MacDonald K, Abraham I. “Real-life” effectiveness studies of omalizumab in adult patients with severe allergic asthma: meta-analysis. J Allergy Clin Immunol Pract. 2017;5:1362–70.e2.CrossRefGoogle Scholar
  11. Andorf S, Purington N, Block WM, Long AJ, Tupa D, Brittain E, Spergel AR, Desai M, Galli SJ, Nadeau KC, Chinthrajah RS. Anti-IgE treatment with oral immunotherapy in multifood allergic participants: a double-blind, randomised, controlled trial. Lancet Gastroenterol Hepatol. 2018;3:85–94.CrossRefGoogle Scholar
  12. Assa’ad AH, Gupta SK, Collins MH, Thomson M, Heath AT, Smith DA, Perschy TL, Jurgensen CH, Ortega HG, Aceves SS. An antibody against IL-5 reduces numbers of esophageal intraepithelial eosinophils in children with eosinophilic esophagitis. Gastroenterology. 2011;141:1593–604.CrossRefGoogle Scholar
  13. AstraZeneca. AstraZeneca provides update on tralokinumab Phase III programme in severe, uncontrolled asthma. In: 2017.
  14. Ayres JG, Higgins B, Chilvers ER, Ayre G, Blogg M, Fox H. Efficacy and tolerability of anti-immunoglobulin E therapy with omalizumab in patients with poorly controlled (moderate-to-severe) allergic asthma. Allergy Eur J Allergy Clin Immunol. 2004;59:701–8.CrossRefGoogle Scholar
  15. Bachert C, Mannent L, Naclerio RM, Mullol J, Ferguson BJ, Gevaert P, Hellings P, Jiao L, Wang L, Evans RR, Pirozzi G, Graham NM, Swanson B, Hamilton JD, Radin A, Gandhi NA, Stahl N, Yancopoulos GD, Sutherland ER. Effect of subcutaneous dupilumab on nasal polyp burden in patients with chronic sinusitis and nasal polyposis. JAMA. 2016;315:469.CrossRefGoogle Scholar
  16. Barnes PJ. Therapeutic approaches to asthma-chronic obstructive pulmonary disease overlap syndromes. J Allergy Clin Immunol. 2015;136:531–45.CrossRefGoogle Scholar
  17. Barranco P, Phillips-Angles E, Dominguez-Ortega J, Quirce S. Dupilumab in the management of moderate-to-severe asthma: the data so far. Ther Clin Risk Manag. 2017;13:1139–49.CrossRefGoogle Scholar
  18. Beck LA, Thaçi D, Hamilton JD, Graham NM, Bieber T, Rocklin R, Ming JE, Ren H, Kao R, Simpson E, Ardeleanu M, Weinstein SP, Pirozzi G, Guttman-Yassky E, Suárez-Fariñas M, Hager MD, Stahl N, Yancopoulos GD, Radin AR. Dupilumab treatment in adults with moderate-to-severe atopic dermatitis. N Engl J Med. 2014;371:130–9.CrossRefGoogle Scholar
  19. Bel EH, Wenzel SE, Thompson PJ, Prazma CM, Keene ON, Yancey SW, Ortega HG, Pavord ID. Oral glucocorticoid-sparing effect of mepolizumab in eosinophilic asthma. N Engl J Med. 2014;371:1189–97.CrossRefGoogle Scholar
  20. Bjermer L, Lemiere C, Maspero J, Weiss S, Zangrilli J, Germinaro M. Reslizumab for inadequately controlled asthma with elevated blood eosinophil levels: a randomized phase 3 study. Chest. 2016;150:789–98.CrossRefGoogle Scholar
  21. Bleecker ER, FitzGerald JM, Chanez P, Papi A, Weinstein SF, Barker P, Sproule S, Gilmartin G, Aurivillius M, Werkström V, Goldman M. Efficacy and safety of benralizumab for patients with severe asthma uncontrolled with high-dosage inhaled corticosteroids and long-acting β2-agonists (SIROCCO): a randomised, multicentre, placebo-controlled phase 3 trial. Lancet. 2016;388:2115–27.CrossRefGoogle Scholar
  22. Boulet L-P, Chapman KR, Côté J, Kalra S, Bhagat R, Swystun VA, Laviolette M, Cleland LD, Deschesnes F, Su JQ, DeVault A, Fick RB Jr, Cockcroft DW. Inhibitory effects of an anti-lgE antibody E25 on allergen – induced early asthmatic response. Am J Respir Crit Care Med. 1997;155:1835. Scholar
  23. Bousquet J, Wenzel S, Holgate S, Lumry W, Freeman P, Fox H. Predicting response to omalizumab, an anti-IgE antibody, in patients with allergic asthma. Chest. 2004;125:1378–86.CrossRefGoogle Scholar
  24. Braunstahl GJ, Chen CW, Maykut R, Georgiou P, Peachey G, Bruce J. The eXpeRience registry: the “real-world” effectiveness of omalizumab in allergic asthma. Respir Med. 2013;107:1141–51.CrossRefGoogle Scholar
  25. Brightling CE, Chanez P, Leigh R, O’Byrne PM, Korn S, She D, May RD, Streicher K, Ranade K, Piper E. 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.CrossRefGoogle Scholar
  26. Brownell J, Casale TB. Anti-IgE therapy. Immunol Allergy Clin N Am. 2004;24:551–68.CrossRefGoogle Scholar
  27. Busse W, Corren J, Lanier BQ, McAlary M, Fowler-Taylor A, Cioppa GD, Gupta N. Omalizumab, anti-IgE recombinant humanized monoclonal antibody, for the treatment of severe allergic asthma. J Allergy Clin Immunol. 2001;108:184–90.CrossRefGoogle Scholar
  28. Busse WW, Israel E, Nelson HS, Baker JW, Charous L, Young DY, Vexler V, Shames RS. Daclizumab improves asthma control in patients with moderate to severe persistent asthma: a randomized, controlled trial. Am J Respir Crit Care Med. 2008;178:1002–8.CrossRefGoogle Scholar
  29. Busse WW, Morgan WJ, Gergen PJ, Mitchell HE, Sorkness C. Randomized trial of omalizumab (anti-IgE) for asthma in inner-city children. N Engl J Med. 2011;364:1005–15.CrossRefGoogle Scholar
  30. Busse W, Spector S, Rosén K, Wang Y, Alpan O. High eosinophil count: a potential biomarker for assessing successful omalizumab treatment effects. J Allergy Clin Immunol. 2013;132:485. Scholar
  31. Cahill KN, Katz HR, Cui J, Lai J, Kazani S, Crosby-Thompson A, Garofalo D, Castro M, Jarjour N, DiMango E, Erzurum S, Trevor JL, Shenoy K, Chinchilli VM, Wechsler ME, Laidlaw TM, Boyce JA, Israel E. KIT inhibition by imatinib in patients with severe refractory asthma. N Engl J Med. 2017;376:1911–20.CrossRefGoogle Scholar
  32. Casale TB, Condemi J, LaForce C, Nayak A, Rowe M, Watrous M, McAlary M, Fowler-Taylor A, Racine A, Gupta N, Fick R, Della Cioppa G. Effect of omalizumab on symptoms of seasonal allergic rhinitis. JAMA. 2001;286:2956–67.CrossRefGoogle Scholar
  33. Casale TB, Bernstein JA, Maurer M, Saini SS, Trzaskoma B, Chen H, Grattan CE, Gimenéz-Arnau A, Kaplan AP, Rosén K. Similar efficacy with omalizumab in chronic idiopathic/spontaneous urticaria despite different background therapy. J Allergy Clin Immunol Pract. 2015;3:743–50.e1.CrossRefGoogle Scholar
  34. Castro M, Mathur S, Hargreave F, Boulet LP, Xie F, Young J, Jeffrey Wilkins H, Henkel T, Nair P. Reslizumab for poorly controlled, eosinophilic asthma: a randomized, placebo-controlled study. Am J Respir Crit Care Med. 2011;184:1125–32.CrossRefGoogle Scholar
  35. Castro M, Zangrilli J, Wechsler ME, Bateman ED, Brusselle GG, Bardin P, Murphy K, Maspero JF, O’Brien C, Korn S. 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;3:355–66.CrossRefGoogle Scholar
  36. Chervinsky P, Casale T, Townley R, Tripathy I, Hedgecock S, Fowler-Taylor A, Shen H, Fox H. Omalizumab, an anti-IgE antibody, in the treatment of adults and adolescents with perennial allergic rhinitis. Ann Allergy Asthma Immunol. 2003;91:160–7.CrossRefGoogle Scholar
  37. Chupp GL, Bradford ES, Albers FC, Bratton DJ, Wang-Jairaj J, Nelsen LM, Trevor JL, Magnan A, ten Brinke A. Efficacy of mepolizumab add-on therapy on health-related quality of life and markers of asthma control in severe eosinophilic asthma (MUSCA): a randomised, double-blind, placebo-controlled, parallel-group, multicentre, phase 3b trial. Lancet Respir Med. 2017;5:390–400.CrossRefGoogle Scholar
  38. Cockle SM, Stynes G, Gunsoy NB, Parks D, Alfonso-Cristancho R, Wex J, Bradford ES, Albers FC, Willson J. Comparative effectiveness of mepolizumab and omalizumab in severe asthma: an indirect treatment comparison. Respir Med. 2017;123:140–8.CrossRefGoogle Scholar
  39. Corren J, Casale T, Deniz Y, Ashby M. Omalizumab, a recombinant humanized anti-IgE antibody, reduces asthma-related emergency room visits and hospitalizations in patients with allergic asthma. J Allergy Clin Immunol. 2003;111:87–90.CrossRefGoogle Scholar
  40. Corren J, Weinstein S, Janka L, Zangrilli J, Garin M. Phase 3 study of reslizumab in patients with poorly controlled asthma: effects across a broad range of eosinophil counts. Chest. 2016;150:799–810.CrossRefGoogle Scholar
  41. Corren J, Parnes JR, Wang L, Mo M, Roseti SL, Griffiths JM, van der Merwe R. Tezepelumab in adults with uncontrolled asthma. N Engl J Med. 2017;377: 936–46.CrossRefGoogle Scholar
  42. Cox L, Platts-Mills TAE, Finegold I, Schwartz LB, Simons FER, Wallace DV. 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. 2007;120:1373–7.CrossRefGoogle Scholar
  43. Fahy JV, Fleming HE, Wong HH, Llu JT, Su JQ, Reimann J, Fick RB, Boushey HA. The effect of an anti-lgE monoclonal antibody on the early- and late-phase responses to allergen inhalation in asthmatic subjects. Am J Respir Crit Care Med. 1997;155:1828–34.CrossRefGoogle Scholar
  44. Farne HA, Wilson A, Powell C, Bax L, Milan SJ. Anti-IL5 therapies for asthma. Cochrane Database Syst Rev. 2017;9:CD010834.PubMedGoogle Scholar
  45. Ferguson GT, FitzGerald JM, Bleecker ER, Laviolette M, Bernstein D, LaForce C, Mansfield L, Barker P, Wu Y, Jison M, Goldman M. Benralizumab for patients with mild to moderate, persistent asthma (BISE): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Respir Med. 2017;5:568–76.CrossRefGoogle Scholar
  46. FitzGerald JM, Bleecker ER, Nair P, Korn S, Ohta K, Lommatzsch M, Ferguson GT, Busse WW, Barker P, Sproule S, Gilmartin G, Werkström V, Aurivillius M, Goldman M. Benralizumab, an anti-interleukin-5 receptor α monoclonal antibody, as add-on treatment for patients with severe, uncontrolled, eosinophilic asthma (CALIMA): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet. 2016;388: 2128–41.CrossRefGoogle Scholar
  47. FitzGerald JM, Bleecker ER, Menzies-Gow A, Zangrilli JG, Hirsch I, Metcalfe P, Newbold P, Goldman M. Predictors of enhanced response with benralizumab for patients with severe asthma: pooled analysis of the SIROCCO and CALIMA studies. Lancet Respir Med. 2017;2600:1–14.Google Scholar
  48. Gauvreau GM, Boulet LP, Leigh R, Cockcroft DW, Killian KJ, Davis BE, Deschesnes F, Watson RM, Swystun V, Kärrman Mardh C, Wessman P, Jorup C, Aurivillius M, O’Byrne PM. A nonsteroidal glucocorticoid receptor agonist inhibits allergen-induced late asthmatic responses. Am J Respir Crit Care Med. 2015;191:161–7.CrossRefGoogle Scholar
  49. Genentech. FDA Approves Xolair, Biotechnology Breakthrough for Asthma. 2003.
  50. Gergen PJ, Mitchell H, Lynn H. Understanding the seasonal pattern of childhood asthma: results from the National Cooperative Inner-City Asthma Study (NCICAS). J Pediatr. 2002;141:631–6.CrossRefGoogle Scholar
  51. Gevaert P, Van Bruaene N, Cattaert T, Van Steen K, Van Zele T, Acke F. Mepolizumab, a humanized anti-IL-5 mAb, as a treatment option for severe nasal polyposis. J Allergy Clin Immunol. 2011;128:989–95.CrossRefGoogle Scholar
  52. Gevaert P, Calus L, Van Zele T, Blomme K, De Ruyck N, Bauters W, Hellings P, Brusselle G, De Bacquer D, van Cauwenberge P, Bachert C. Omalizumab is effective in allergic and nonallergic patients with nasal polyps and asthma. J Allergy Clin Immunol. 2013;131:110–6.e1.CrossRefGoogle Scholar
  53. Gonem S, Berair R, Singapuri A, Hartley R, Laurencin MFM, Bacher G, Holzhauer B, Bourne M, Mistry V, Pavord ID, Mansur AH, Wardlaw AJ, Siddiqui SH, Kay RA, Brightling CE. Fevipiprant, a prostaglandin D2 receptor 2 antagonist, in patients with persistent eosinophilic asthma: a single-centre, randomised, double-blind, parallel-group, placebo-controlled trial. Lancet Respir Med. 2016;4:699–707.CrossRefGoogle Scholar
  54. 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.CrossRefGoogle Scholar
  55. Haldar P, Brightling CE, Singapuri A, Hargadon B, Gupta S, Monteiro W, Bradding P, Green RH, Wardlaw AJ, Ortega H, Pavord ID. Outcomes after cessation of mepolizumab therapy in severe eosinophilic asthma: a 12-month follow-up analysis. J Allergy Clin Immunol. 2014;133:921–3.CrossRefGoogle Scholar
  56. Hanania NA, Wenzel S, Roseń K, Hsieh HJ, Mosesova S, Choy DF, Lal P, Arron JR, Harris JM, Busse W. 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.CrossRefGoogle Scholar
  57. Hirai H, Tanaka K, Yoshie O. Prostaglandin D2 selectively induces chemotaxis in T helper type 2 cells, eosinophils, and basophils via seven-transmembrane receptor CRTH2. J Exp Med. 2001;193:255–61.CrossRefGoogle Scholar
  58. Holgate S, Bousquet J, Wenzel S, Fox H, Liu J, Castellsague J. Efficacy of omalizumab, an anti-immunoglobulin E antibody, in patients with allergic asthma at high risk of serious asthma-related morbidity and mortality. Curr Med Res Opin. 2001;17:233–40.CrossRefGoogle Scholar
  59. Humbert M, Beasley R, Ayres J, Slavin R, Hébert J, Bousquet J, Beeh K-M, Ramos S, Canonica GW, Hedgecock S, Fox H, Blogg M, Surrey K. 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. Allergy Eur J Allergy Clin Immunol. 2005;60:309–16.CrossRefGoogle Scholar
  60. Iribarren C, Rahmaoui A, Long AA, Szefler SJ, Bradley MS, Carrigan G, Eisner MD, Chen H, Omachi TA, Farkouh ME, Rothman KJ. Cardiovascular and cerebrovascular events among patients receiving omalizumab: results from EXCELS, a prospective cohort study in moderate to severe asthma. J Allergy Clin Immunol. 2017;139:1489–95.e5.CrossRefGoogle Scholar
  61. Johnston NW, Johnston SL, Duncan JM, Greene JM, Kebadze T, Keith PK, Roy M, Waserman S, Sears MR. The September epidemic of asthma exacerbations in children: a search for etiology. J Allergy Clin Immunol. 2005;115:132–8.CrossRefGoogle Scholar
  62. Kaplan AP, Joseph K, Maykut RJ, Geba GP, Zeldin RK. Treatment of chronic autoimmune urticaria with omalizumab. J Allergy Clin Immunol. 2008;122: 569–73.CrossRefGoogle Scholar
  63. Kaplan A, Ledford D, Ashby M, Canvin J, Zazzali JL, Conner E, Veith J, Kamath N, Staubach P, Jakob T, Stirling RG, Kuna P, Berger W, Maurer M, Rosén K. Omalizumab in patients with symptomatic chronic idiopathic/spontaneous urticaria despite standard combination therapy. J Allergy Clin Immunol. 2013;132:101–9.CrossRefGoogle Scholar
  64. Knutsen R. Novartis aims to bring first oral asthma drug to market in two decades. In: MM&M. 2017.
  65. Kraft M, Martin R, Lazarus S. Airway tissue mast cells in persistent asthma: predictor of treatment failure when patients discontinue inhaled corticosteroids. Chest. 2003;124:42.CrossRefGoogle Scholar
  66. Krug N, Hohlfeld JM, Kirsten A-M, Kornmann O, Beeh KM, Kappeler D, Korn S, Ignatenko S, Timmer W, Rogon C, Zeitvogel J, Zhang N, Bille J, Homburg U, Turowska A, Bachert C, Werfel T, Buhl R, Renz J, Garn H, Renz H. Allergen-induced asthmatic responses modified by a GATA3-specific DNAzyme. N Engl J Med. 2015;372:1987–95.CrossRefGoogle Scholar
  67. Krug N, Hohlfeld JM, Buhl R, Renz J, Garn H, Renz H. Blood eosinophils predict therapeutic effects of a GATA3-specific DNAzyme in asthma patients. J Allergy Clin Immunol. 2017;140:625–8.e5.CrossRefGoogle Scholar
  68. Kuna P, Aurivillius M, Jorup C, Prothon S. Efficacy and tolerability of an inhaled selective glucocorticoid receptor modulator – AZD5423 – in chronic obstructive pulmonary disease patients: phase II study results. Basic Clin Pharmacol Toxicol. 2017;121:279–89.CrossRefGoogle Scholar
  69. Lanier B, Bridges T, Kulus M, Taylor AF, Berhane I, Vidaurre CF. Omalizumab for the treatment of exacerbations in children with inadequately controlled allergic (IgE-mediated) asthma. J Allergy Clin Immunol. 2009;124:1210–6.CrossRefGoogle Scholar
  70. Ledford D, Busse W, Trzaskoma B, Omachi TA, Rosén K, Chipps BE, Luskin AT, Solari PG. A randomized multicenter study evaluating Xolair persistence of response after long-term therapy. J Allergy Clin Immunol. 2017;140:162–9.e2.CrossRefGoogle Scholar
  71. Li J, Wang F, Lin C, Du J, Xiao B, Du C, Sun J. The efficacy and safety of reslizumab for inadequately controlled asthma with elevated blood eosinophil counts: a systematic review and meta-analysis. J Asthma. 2017;54:300–7.CrossRefGoogle Scholar
  72. Lieberman PL, Umetsu DT, Carrigan GJ, Rahmaoui A. Anaphylactic reactions associated with omalizumab administration: analysis of a case-control study. J Allergy Clin Immunol. 2016;138:913–5.e2.CrossRefGoogle Scholar
  73. Long A, Rahmaoui A, Rothman KJ, Guinan E, Eisner M, Bradley MS, Iribarren C, Chen H, Carrigan G, Rosén K, Szefler SJ. Incidence of malignancy in patients with moderate-to-severe asthma treated with or without omalizumab. J Allergy Clin Immunol. 2014;134:560. Scholar
  74. Lugogo N, Domingo C, Chanez P, Leigh R, Gilson MJ, Price RG, Yancey SW, Ortega HG. Long-term efficacy and safety of mepolizumab in patients with severe eosinophilic asthma: a multi-center, open-label, phase IIIb study. Clin Ther. 2016;38:2058–70.e1.CrossRefGoogle Scholar
  75. Magnan A, Bourdin A, Prazma CM, Albers FC, Price RG, Yancey SW, Ortega H. Treatment response with mepolizumab in severe eosinophilic asthma patients with previous omalizumab treatment. Allergy Eur J Allergy Clin Immunol. 2016;71:1335–44.CrossRefGoogle Scholar
  76. Maurer M, Rosén K, Hsieh H-J, Saini S, Grattan C, Gimenéz-Arnau A, Agarwal S, Doyle R, Canvin J, Kaplan A, Casale T. Omalizumab for the treatment of chronic idiopathic or spontaneous urticaria. N Engl J Med. 2013;368:924–35.CrossRefGoogle Scholar
  77. Milgrom H, Fick RB Jr, Su JQ, Reimann JD, Bush RK, Watrous ML, Metzger WJ. Treatment of allergic asthma with monoclonal anti-IgE antibody. N Engl J Med. 1999;341:1966–73.CrossRefGoogle Scholar
  78. Milgrom H, Berger W, Nayak A, Gupta N, Pollard S, McAlary M, Taylor AF, Rohane P. Treatment of childhood asthma with anti-immunoglobulin E antibody (Omalizumab). Pediatrics. 2001;108:e36.CrossRefGoogle Scholar
  79. Nadeau KC, Schneider LC, Hoyte L, Borras I, Umetsu DT. Rapid oral desensitization in combination with omalizumab therapy in patients with cow’s milk allergy. J Allergy Clin Immunol. 2011;127:1622–4.CrossRefGoogle Scholar
  80. 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. N Engl J Med. 2009;360:985–93.CrossRefGoogle Scholar
  81. Nair P, Wenzel S, Rabe KF, Bourdin A, Lugogo NL, Kuna P, Barker P, Sproule S, Ponnarambil S, Goldman M. Oral glucocorticoid–sparing effect of benralizumab in severe asthma. N Engl J Med. 2017;376:2448–58.CrossRefGoogle Scholar
  82. Noga O, Hanf G, Kunkel G. Immunological and clinical changes in allergic asthmatics following treatment with omalizumab. Int Arch Allergy Immunol. 2003;131:46–52.CrossRefGoogle Scholar
  83. Normansell R, Walker S, Milan SJ, Walters EH, Nair P. Omalizumab for asthma in adults and children (review). Cochrane Database Syst Rev. 2014.
  84. Ortega HG, Liu MC, Pavord ID, Brusselle GG, FitzGerald M, Chetta A, Humbert M, Katz LE, Keene ON, Yancey SW, Chanez P. Mepolizumab treatment in patients with severe eosinophilic asthma. N Engl J Med. 2014;371:1198–207.CrossRefGoogle Scholar
  85. Ortega HG, Yancey SW, Mayer B, Gunsoy NB, Keene ON, Bleecker ER, Brightling CE, Pavord ID. Severe eosinophilic asthma treated with mepolizumab stratified by baseline eosinophil thresholds: a secondary analysis of the DREAM and MENSA studies. Lancet Respir Med. 2016;4:549–56.CrossRefGoogle Scholar
  86. Otani IM, Anilkumar AA, Newbury RO, Bhagat M, Beppu LY, Dohil R, Broide DH, Aceves SS. Anti-IL-5 therapy reduces mast cell and IL-9 cell numbers in pediatric patients with eosinophilic esophagitis. J Allergy Clin Immunol. 2013;131:1576–82.e2.CrossRefGoogle Scholar
  87. Paller AS, Kabashima K, Bieber T. Therapeutic pipeline for atopic dermatitis: end of the drought? J Allergy Clin Immunol. 2017;140:633–43.CrossRefGoogle Scholar
  88. 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.CrossRefGoogle Scholar
  89. Penn R, Mikula S. The role of anti-IgE immunoglobulin therapy in nasal polyposis: a pilot study. Am J Rhinol. 2007;21:428–32.CrossRefGoogle Scholar
  90. Pinto J, Mehta N, DiTineo M, Wang J, Baroody F, Naclerio R. A randomized, double-blind, placebo-controlled trial of anti-IgE for chronic rhinosinusitis. Rhinology. 2010;48:318–24.PubMedGoogle Scholar
  91. Piper E, Brightling C, Niven R, Oh C, Faggioni R, Poon K, She D, Kell C, May RD, Geba GP, Molfino NA. A phase II placebo-controlled study of tralokinumab in moderate-to-severe asthma. Eur Respir J. 2013;41: 330–8.CrossRefGoogle Scholar
  92. Polk BI, Rosenwasser LJ. Biological therapies of immunologic diseases: strategies for Immunologic Interventions. Immunol Allergy Clin North Am. 2017;37: 247–59.CrossRefGoogle Scholar
  93. Rodrigo GJ, Neffen H, Castro-Rodriguez JA. Efficacy and safety of subcutaneous omalizumab vs placebo as add-on therapy to corticosteroids for children and adults with asthma: a systematic review. Chest. 2011;139:28–35.CrossRefGoogle Scholar
  94. Saini SS, Bindslev-Jensen C, Maurer M, Grob JJ, Baskan EB, Bradley MS, Canvin J, Rahmaoui A, Georgiou P, Alpan O, Spector S, Rosén K. Efficacy and safety of omalizumab in patients with chronic idiopathic/spontaneous urticaria who remain symptomatic on h 1 antihistamines: a randomized, placebo-controlled study. J Invest Dermatol. 2015;135:67–75.CrossRefGoogle Scholar
  95. Sanofi. Evaluation of dupilumab in patients with persistent asthma (Liberty Asthma Quest). In: 2017a.
  96. Sanofi. Evaluation of dupilumab in patients with severe steroid dependent asthma (VENTURE). In: 2017b.Google Scholar
  97. Sanofi. Evaluation of dupilumab in children with uncontrolled asthma (VOYAGE). In: 2018a.
  98. Sanofi. Evaluation of dupilumab’s effects on airway inflammation in patients with asthma (EXPEDITION). In: 2018b.
  99. Sanofi. Long-term safety evaluation of dupilumab in patients with asthma (LIBERTY ASTHMA TRAVERSE). In: ClinicalTrialsgov. 2018c.Google Scholar
  100. Sheikh J. Autoantibodies to the high-affinity IgE receptor in chronic urticaria: how important are they? Curr Opin Allergy Clin Immunol. 2005;5:403–7.CrossRefGoogle Scholar
  101. Silkoff PE, Romero FA, Gupta N, Townley RG, Milgrom H. Exhaled nitric oxide in children with asthma receiving xolair (omalizumab), a monoclonal anti-immunoglobulin E antibody. Pediatrics. 2004;113:e308–12.CrossRefGoogle Scholar
  102. Simpson EL, Bieber T, Guttman-Yassky E, Beck LA, Blauvelt A, Cork MJ, Silverberg JI, Deleuran M, Kataoka Y, Lacour J-P, Kingo K, Worm M, Poulin Y, Wollenberg A, Soo Y, Graham NMH, Pirozzi G, Akinlade B, Staudinger H, Mastey V, Eckert L, Gadkari A, Stahl N, Yancopoulos GD, Ardeleanu M. Two phase 3 trials of dupilumab versus placebo in atopic dermatitis. N Engl J Med. 2016;375:2335–48.CrossRefGoogle Scholar
  103. Solèr M, Matz J, Townley R, Buhl R, O’Brien J, Fox H, Thirlwell J, Gupta N, Della Cioppa G. The anti-IgE antibody omalizumab reduces exacerbations and steroid requirement in allergic asthmatics. Eur Respir J. 2001;18:254–61.CrossRefGoogle Scholar
  104. Spergel JM, Rothenberg ME, Collins MH, Furuta GT, Markowitz JE, Fuchs G III, O’Gorman MA, Abonia JP, Young J, Henkel T, Wilkins HJ, Liacouras CA. Reslizumab in children and adolescents with eosinophilic esophagitis: results of a double-blind, randomized, placebo-controlled trial. J Allergy Clin Immunol. 2012;129:456–63.e3.CrossRefGoogle Scholar
  105. Stein ML, Collins MH, Villanueva JM, Kushner JP, Putnam PE, Buckmeier BK, Filipovich AH, Assa’ad AH, Rothenberg ME. Anti-IL-5 (mepolizumab) therapy for eosinophilic esophagitis. J Allergy Clin Immunol. 2006;118:1312–9.CrossRefGoogle Scholar
  106. Steinke JW, Rosenwasser LJ, Borish L. Cytokines in allergic inflammation. In: Adkinson Jr NF, Bochner B, Burks AW, Busse W, Holgate S, Lemanske R, O’Hehir RE, editors. Middleton’s allergy principles and practice. 8th ed. Philadelphia: Elsevier; 2014. p. 65–83.Google Scholar
  107. Stokes JR, Casale TB. Characterization of asthma endotypes: implications for therapy. Ann Allergy Asthma Immunol. 2016;117:121–5.CrossRefGoogle Scholar
  108. Straumann A, Conus S, Grzonka P, Kita H, Kephart G, Bussmann B, Beglinger C, Smith DA, Patel J, Byrne M, Simon H-U. Anti-interleukin-5 antibody treatment (mepolizumab) in active eosinophilic oesophagitis: a randomised, placebo-controlled, double-blind trial. Gut. 2010;59:21–30.CrossRefGoogle Scholar
  109. Teach SJ, Gill MA, Togias A, Sorkness CA, Arbes SJ, Calatroni A, Wildfire JJ, Gergen PJ, Cohen RT, Pongracic JA, Kercsmar CM, Khurana Hershey GK, Gruchalla RS, Liu AH, Zoratti EM, Kattan M, Grindle KA, Gern JE, Busse WW, Szefler SJ. Preseasonal treatment with either omalizumab or an inhaled corticosteroid boost to prevent fall asthma exacerbations. J Allergy Clin Immunol. 2015;136: 1476–85.CrossRefGoogle Scholar
  110. Tsabouri S, Tseretopoulou X, Priftis K, Ntzani EE. Omalizumab for the treatment of inadequately controlled allergic rhinitis: a systematic review and meta-analysis of randomized clinical trials. J Allergy Clin Immunol Pract. 2014;2:332–40.CrossRefGoogle Scholar
  111. Wenzel S. Dupilumab compassionate use study. In: 2017.Google Scholar
  112. 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, Vancopoulos GD, Graham N, Pirozzi G. Dupilumab in persistent asthma with elevated eosinophil levels. N Engl J Med. 2013;368:2455–66.CrossRefGoogle Scholar
  113. Wenzel S, Castro M, Corren J, Maspero J, Wang L, Zhang B, Pirozzi G, Rand Sutherland E, Evans RR, Joish VN, Eckert L, Graham NMH, Stahl N, Yancopoulos GD, Louis-Tisserand M, Teper A. Dupilumab efficacy and safety in adults with uncontrolled persistent asthma despite use of medium-to-high-dose inhaled corticosteroids plus a long-acting β2 agonist: a randomised double-blind placebo-controlled pivotal phase 2b dose-ranging trial. Lancet (London, England). 2016;388:31–44.CrossRefGoogle Scholar
  114. Wood RA, Kim JS, Lindblad R, Nadeau K, Henning AK, Dawson P, Plaut M, Sampson HA. A randomized, double-blind, placebo-controlled study of omalizumab combined with oral immunotherapy for the treatment of cow’s milk allergy. J Allergy Clin Immunol. 2016;137:1103–10.e11.CrossRefGoogle Scholar
  115. Woodruff PG, Modrek B, Choy DF, Jia G, Abbas AR, Ellwanger A, Arron JR, Koth LL, Fahy JV. T-helper type 2-driven inflammation defines major subphenotypes of asthma. Am J Respir Crit Care Med. 2009;180:388–95.CrossRefGoogle Scholar
  116. Xue L, Gyles S, Wettey F. Prostaglandin D2 causes preferential induction of proinflammatory Th2 cytokine production through an action on chemoattractant receptor-like molecule expressed on Th2 cells. J Immunol. 2005;175:6531–6.CrossRefGoogle Scholar
  117. Xue L, Barrow A, Pettipher R. Novel function of CRTH2 in preventing apoptosis of human Th2 cells through activation of the phosphatidylinositol 3-kinase pathway. J Immunol. 2009;182:7580–6.CrossRefGoogle Scholar
  118. Yancey SW, Ortega HG, Keene ON, Mayer B, Gunsoy NB, Brightling CE, Bleecker ER, Haldar P, Pavord ID. Meta-analysis of asthma-related hospitalization in mepolizumab studies of severe eosinophilic asthma. J Allergy Clin Immunol. 2017;139:1167–75.e2.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2018

Authors and Affiliations

  1. 1.Department of PediatricsWashington University School of Medicine in St. LouisSt. LouisUSA

Section editors and affiliations

  • Massoud Mahmoudi
    • 1
  • Timothy Craig
    • 2
  • Dennis K. Ledford
    • 3
  1. 1.Division of General Medicine/Department of MedicineUniversity of CaliforniaSan FranciscoUSA
  2. 2.Department of Medicine and PediatricsPenn State College of MedicineHersheyUSA
  3. 3.Division of Allergy & Immunology, Dept. of Internal MedicineUniversity of South Florida Morsani College of Medicine, James A Haley Veterans' Hospital, Asthma and Immunology Associates of Tampa BayTampaUSA

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