2018 Section 5 - Rhinology and Allergic Disorders

CASALE

J ALLERGY CLIN IMMUNOL MAY 2017

improved considerably with the advent of the development of mAbs and other biologics.

12. van den Berge M, Pauw RG, de Monchy JG, van Minnen CA, Postma DS, Kerstjens HA. Beneficial effects of treatment with anti-IgE antibodies (omalizumab) in a pa- tient with severe asthma and negative skin-prick test results. Chest 2011;139:190-3 . 13. Gevaert P, Calus L, Van Zele T, Blomme K, De Ruyck N, Bauters W, et al. Oma- lizumab is effective in allergic and nonallergic patients with nasal polyps and asthma. J Allergy Clin Immunol 2013;131:110-6.e1 . 14. Garcia G, Magnan A, Chiron R, Contin-Bordes C, Berger P, Taille C, et al. A proof-of-concept, randomized, controlled trial of omalizumab in patients with se- vere, difficult-to-control, nonatopic asthma. Chest 2013;144:411-9 . 15. Stokes JR, Casale TB. The use of anti-IgE therapy beyond allergic asthma. J Allergy Clin Immunol Pract 2015;3:162-6 . 16. Ortega HG, Liu MC, Pavord ID, Brusselle GG, FitzGerald JM, Chetta A, et al. Mepolizumab treatment in patients with severe eosinophilic asthma. N Engl J Med 2014;371:1198-207 . 17. Pavord ID, Korn S, Howarth P, Bleecker ER, Buhl R, Keene ON, et al. Mepoli- zumab for severe eosinophilic asthma (DREAM): a multicentre, double-blind, placebo-controlled trial. Lancet 2012;380:651-9 . 18. Nair P, Pizzichini MM, Kjarsgaard M, Inman MD, Efthimiadis A, Pizzichini E, et al. Mepolizumab for prednisone-dependent asthma with sputum eosinophilia. N Engl J Med 2009;360:985-93 . 19. Bel EH, Wenzel SE, Thompson PJ, Prazma CM, Keene ON, Yancey SW, et al. Oral glucocorticoid-sparing effect of mepolizumab in eosinophilic asthma. N Engl J Med 2014;371:1189-97 . 20. Haldar P, Brightling CE, Singapuri A, Hargadon B, Gupta S, Monteiro W, 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 . 21. Castro M, Zangrilli J, Wechsler ME, Bateman ED, Brusselle GG, Bardin P, 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;3:355-66 . 22. 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 eosin- ophil counts. Chest 2016;150:799-810 . 23. Bjermer L, Lemiere C, Maspero J, Weiss S, Zangrilli J, Germinaro M. Reslizu- mab for inadequately controlled asthma with elevated blood eosinophil levels: a randomized phase 3 study. Chest 2016;150:789-98 . 24. Gauvreau GM, Harris JM, Boulet LP, Scheerens H, Fitzgerald JM, Putnam WS, et al. Targeting membrane-expressed IgE B cell receptor with an antibody to the M1 prime epitope reduces IgE production. Sci Transl Med 2014;6:243ra85 . 25. Harris JM, Maciuca R, Bradley MS, Cabanski CR, Scheerens H, Lim J, et al. A randomized trial of the efficacy and safety of quilizumab in adults with inade- quately controlled allergic asthma. Respir Res 2016;17:29 . 26. Rosenwasser LJ, Busse WW, Lizambri RG, Olejnik TA, Totoritis MC. Allergic asthma and an anti-CD23 mAb (IDEC-152): results of a phase I, single-dose, dose-escalating clinical trial. J Allergy Clin Immunol 2003;112:563-70 . 27. Gauvreau GM, Arm JP, Boulet LP, Leigh R, Cockcroft DW, Davis BE, et al. Ef- ficacy and safety of multiple doses of QGE031 (ligelizumab) versus omalizumab and placebo in inhibiting allergen-induced early asthmatic responses. J Allergy Clin Immunol 2016;138:1051-9 . 28. Bleecker ER, FitzGerald JM, Chanez P, Papi A, Weinstein SF, Barker P, et al. Ef- ficacy and safety of benralizumab for patients with severe asthma uncontrolled with high-dosage inhaled corticosteroids and long-acting b (2)-agonists (SI- ROCCO): a randomised, multicentre, placebo-controlled phase 3 trial. Lancet 2016;388:2115-27 . 29. FitzGerald JM, Bleecker ER, Nair P, Korn S, Ohta K, Lommatzsch M, et al. Ben- ralizumab, an anti-interleukin-5 receptor a monoclonal antibody, as add-on treat- ment for patients with severe, uncontrolled, eosinophilic asthma (CALIMA): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet 2016;388: 2128-41 . 30. Corren J, Lemanske RF, Hanania NA, Korenblat PE, Parsey MV, Arron JR, et al. Lebrikizumab treatment in adults with asthma. N Engl J Med 2011;365:1088-98 . 31. Hanania NA, Korenblat P, Chapman KR, Bateman ED, Kopecky P, Paggiaro P, 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;4:781-96 . 32. Piper E, Brightling C, Niven R, Oh C, Faggioni R, Poon K, et al. A phase II placebo-controlled study of tralokinumab in moderate-to-severe asthma. Eur Re- spir J 2013;41:330-8 . 33. Brightling CE, Chanez P, Leigh R, O’Byrne PM, Korn S, She D, et al. Efficacy and safety of tralokinumab in patients with severe uncontrolled asthma: a rando- mised, double-blind, placebo-controlled, phase 2b trial. Lancet Respir Med 2015; 3:692-701 . 34. Wenzel S, Castro M, Corren J, Maspero J, Wang L, Zhang B, et al. Dupilumab efficacy and safety in adults with uncontrolled persistent asthma despite use of

What do we know? d IgE plays an important role in the pathogenesis of asthma, urticaria, and nasal polyps (in some patients), providing a rationale for the use of omalizumab. d Blocking IL-5 is effective in treating patients with asthma and some patients with nasal polyps. d Strategies aimed at blocking both IL-4 and IL-13 are important in treating multiple allergic and respiratory diseases, including asthma, atopic dermatitis, and nasal polyps. d IL-1 antagonists are important treatments for CAPSs. What is still unknown? d How to diagnose and optimally treat type 2–low asthma d What biomarkers can be used to predict optimal re- sponses of individual patients with type 2–high asthma to specific type 2–high asthma–targeted biologics d How to induce true immunomodulation of allergic diseases d Whether blocking IL-13 alone will be an effective strategy for asthma management d Whether biologics other than omalizumab will prove effective in patients with chronic spontaneous urticaria REFERENCES 1. Muraro A, Lemanske RF Jr, Hellings PW, Akdis CA, Bieber T, Casale TB, et al. Precision medicine in patients with allergic diseases: airway diseases and atopic dermatitis—PRACTALL document of the European Academy of Allergy and Clinical Immunology and the American Academy of Allergy, Asthma & Immu- nology. J Allergy Clin Immunol 2016;137:1347-58 . 2. Stokes JR, Casale TB. Characterization of asthma endotypes: implications for therapy. Ann Allergy Asthma Immunol 2016;117:121-5 . 3. Berry A, Busse WW. Biomarkers in asthmatic patients: Has their time come to direct treatment? J Allergy Clin Immunol 2016;137:1317-24 . 4. Wenzel SE. Asthma phenotypes: the evolution from clinical to molecular ap- proaches. Nat Med 2012;18:716-25 . 5. 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 . 6. Cowan DC, Taylor DR, Peterson LE, Cowan JO, Palmay R, Williamson A, et al. Biomarker-based asthma phenotypes of corticosteroid response. J Allergy Clin Immunol 2015;135:877-83 . 7. Wenzel S, Ford L, Pearlman D, Spector S, Sher L, Skobieranda F, et al. Dupilu- mab in persistent asthma with elevated eosinophil levels. N Engl J Med 2013;368: 2455-66 . 8. Casale TB, Condemi J, LaForce C, Nayak A, Rowe M, Watrous M, et al. Effect of omalizumab on symptoms of seasonal allergic rhinitis: a randomized controlled trial. JAMA 2001;286:2956-67 . 9. Hanania NA, Wenzel S, Rosen K, Hsieh HJ, Mosesova S, Choy DF, 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 . 10. Busse W, Spector S, Rosen K, Wang Y, Alpan O. High eosinophil count: a poten- tial biomarker for assessing successful omalizumab treatment effects. J Allergy Clin Immunol 2013;132:485-6.e11 . 11. Casale TB, Omachi TA, Trzaskoma B, Rao S, Chou W, Ortiz B, et al. Estimated asthma exacerbation reduction from omalizumab in a severe eosinophilic asthma population. J Allergy Clin Immunol 2015;135:AB1 .

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