Skip to main content
SpringerLink
Log in

Omalizumab for Severe Asthma: Efficacy Beyond the Atopic Patient?

  • Current Opinion
  • Published:
Drugs Aims and scope Submit manuscript

Abstract

Several years ago, omalizumab became commercially available for the treatment of severe asthma. It remains the only monoclonal antibody to be marketed for this purpose. Since then, many studies have been published endorsing its efficacy and effectiveness. Concomitantly, evidence of an overlap between atopic and non-atopic severe asthma has emerged. However, there also appears to be some disagreement regarding the value of omalizumab in the management of non-atopic disease, as some studies have failed to show any benefit in these patients. The recent literature has also sought to identify appropriate prognostic biomarkers for the use of omalizumab, other than immunoglobulin (IgE) levels. This article briefly summarizes the evolution of asthma treatment, the pathophysiology of the condition, and the method of action of omalizumab. The author describes the controlled and uncontrolled studies (also named “real-life studies”) published in adult and pediatric populations in different countries and expresses his view on the current place of the drug in the management of severe allergic asthma. He offers a personal perspective on the recent evidence for the use of omalizumab in non-atopic patients, highlighting the implications for current clinical practice and the gaps in our knowledge. The author justifies his belief that omalizumab is not only an IgE-blocking drug and should be considered as a disease-modifying therapy because of its multiple effects on different biologic pathways. Finally, some areas for future research are indicated.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Banh HL. Unconventional treatment options in severe asthma: an overivew. J Pharm Pharm Sci. 2011;14(3):387–99.

    PubMed  CAS  Google Scholar 

  2. Bush A, Menzies-Gow A. Phenotypic differences between pediatric and adult asthma. Proc Am Thorac Soc. 2009;6(8):712–9.

    Article  PubMed  Google Scholar 

  3. Holgate ST, Polosa R. The mechanisms, diagnosis, and management of severe asthma in adults. Lancet. 2006;368(9537):780–93.

    Article  PubMed  CAS  Google Scholar 

  4. Moore WC, Peters SP. Severe asthma: an overview. J Allergy Clin Immunol. 2006 Mar;117(3):487–94; quiz 495.

  5. de Carvalho-Pinto RM, Cukier A, Angelini L, Antonangelo L, Mauad T, Dolhnikoff M, et al. Clinical characteristics and possible phenotypes of an adult severe asthma population. Respir Med. 2012;106(1):47–56.

    Article  PubMed  Google Scholar 

  6. National Heart, Lung, and Blood Institute, National Institutes of Health. International consensus report on diagnosis and treatment of asthma. Publication no. 92-3091, March 1992. Eur Respir J. 1992;5(5):601–41.

  7. Morjaria JB, Polosa R. Recommendation for optimal management of severe refractory asthma. J Asthma Allergy. 2010;3:43–56.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  8. Domingo C. Ultra-LAMA, ultra-LABA, ultra-inhaled steroids? The future has landed. Arch Bronconeumol. 2013;49(4):131–4.

    Article  PubMed  Google Scholar 

  9. Federal Register, Food and Drug Administration. Biological products: allergenic extracts: implementation of efficacy review. Docket no. 81 N-0096 ed; 1985. p. CRF Parts 600, 10 and 80.

  10. American Academy of Allergy, Asthma and Immunology (AAAAI). The use of standardized allergen extracts. J Allergy Clin Immunol. 1997;99(5):583–6.

    Article  Google Scholar 

  11. Bousquet J, Demoly P. Specific immunotherapy: an optimistic future. Allergy. 2006;61(10):1155–8.

    Article  PubMed  CAS  Google Scholar 

  12. Frew AJ. Sublingual immunotherapy. N Engl J Med. 2008;358(21):2259–64.

    Article  PubMed  CAS  Google Scholar 

  13. Ott H, Sieber J, Brehler R, Folster-Holst R, Kapp A, Klimek L, et al. Efficacy of grass pollen sublingual immunotherapy for three consecutive seasons and after cessation of treatment: the ECRIT study. Allergy. 2009;64(1):179–86.

    Article  PubMed  CAS  Google Scholar 

  14. Pfaar O, Leitzbach S, Hormann K, Klimek L. Cluster protocols in SCIT: enough evidence for practical use? Curr Opin Allergy Clin Immunol. 2010;10(3):188–93.

    Article  PubMed  Google Scholar 

  15. Metzger WJ, Nyce JW. Respirable antisense oligonucleotide (RASON) therapy for allergic asthma. BioDrugs. 1999;12(4):237–43.

    Article  PubMed  CAS  Google Scholar 

  16. Polosa R, Casale T. Monoclonal antibodies for chronic refractory asthma and pipeline developments. Drug Discov Today. 2012;17(11–12):591–9.

    Article  PubMed  CAS  Google Scholar 

  17. Holgate ST, Polosa R. Treatment strategies for allergy and asthma. Nat Rev Immunol. 2008;8(3):218–30.

    Article  PubMed  CAS  Google Scholar 

  18. Domingo C, Pacheco A, Hinojosa M, Bosque M. The relevance of IgE in the pathogenesis of allergy: the effect of an anti-IgE drug in asthma and other diseases. Recent Pat Inflamm Allergy Drug Discov. 2007;1(2):151–64.

    Article  PubMed  CAS  Google Scholar 

  19. Abou Taam R, Scheinmann P, de Blic J. Perspectives pédiatriques des anti-IgE. Rev Fr Allergol Immunol Clin. 2005;45(7):550–4.

    Google Scholar 

  20. Burrows B, Martinez FD, Halonen M, Barbee RA, Cline MG. Association of asthma with serum IgE levels and skin-test reactivity to allergens. N Engl J Med. 1989;320(5):271–7.

    Article  PubMed  CAS  Google Scholar 

  21. Malveaux FJ, Conroy MC, Adkinson NF Jr, Lichtenstein NF. IgE receptors on human basophils: relationship to serum IgE concentration. J Clin Invest. 1978;62(1):176–81.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  22. MacGlashan D Jr, McKenzie-White J, Chichester K, Bochner BS, Davis FM, Schroeder JT, et al. In vitro regulation of FcεRIα expression on human basophils by IgE antibody. Blood. 1998;91(5):1633–43.

    PubMed  CAS  Google Scholar 

  23. Cruse G, Cockerill S, Bradding P. IgE alone promotes human lung mast cell survival through the autocrine production of IL-6. BMC Immunol. 2008;9:2.

    Article  PubMed Central  PubMed  Google Scholar 

  24. Maurer D, Ebner C, Reininger B, Fiebiger E, Kraft D, Kinet JP, et al. The high affinity IgE receptor (FcεRI) mediates IgE-dependent allergen presentation. J Immunol. 1995;154(12):6285–90.

    PubMed  CAS  Google Scholar 

  25. Holloway JA, Holgate ST, Semper AE. Expression of the high-affinity IgE receptor on peripheral blood dendritic cells: differential binding of IgE in atopic asthma. J Allergy Clin Immunol. 2001;107(6):1009–18.

    Article  PubMed  CAS  Google Scholar 

  26. Rajakulasingam K, Durham SR, O’Brien F, Humbert M, Barata LT, Reece L, et al. Enhanced expression of high-affinity IgE receptor (FcεRI) alpha chain in human allergen-induced rhinitis with co-localization to mast cells, macrophages, eosinophils, and dendritic cells. J Allergy Clin Immunol. 1997;100(1):78–86.

    Article  PubMed  CAS  Google Scholar 

  27. Chang TW. The pharmacological basis of anti-IgE therapy. Nat Biotechnol. 2000;18(2):157–62.

    Article  PubMed  CAS  Google Scholar 

  28. MacGlashan DW Jr, Bochner BS, Adelman DC, Jardieu PM, Togias A, McKenzie-White J, et al. Down-regulation of FcεRI expression on human basophils during in vivo treatment of atopic patients with anti-IgE antibody. J Immunol. 1997;158(3):1438–45.

    PubMed  CAS  Google Scholar 

  29. Djukanovic R, Wilson SJ, Kraft M, Jarjour NN, Steel M, Chung KF, et al. Effects of treatment with anti-immunoglobulin E antibody omalizumab on airway inflammation in allergic asthma. Am J Respir Crit Care Med. 2004;170(6):583–93.

    Article  PubMed  Google Scholar 

  30. Prussin C, Griffith DT, Boesel KM, Lin H, Foster B, Casale TB. Omalizumab treatment downregulates dendritic cell FcεRI expression. J Allergy Clin Immunol. 2003;112(6):1147–54.

    Article  PubMed  CAS  Google Scholar 

  31. Humbert M, Beasley R, Ayres J, Slavin R, Hebert J, Bousquet J, et al. 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. 2005;60(3):309–16.

    Article  PubMed  CAS  Google Scholar 

  32. Soler M, Matz J, Townley R, Buhl R, O’Brien J, Fox H, et al. The anti-IgE antibody omalizumab reduces exacerbations and steroid requirement in allergic asthmatics. Eur Respir J. 2001;18(2):254–61.

    Article  PubMed  CAS  Google Scholar 

  33. Busse W, Corren J, Lanier BQ, McAlary M, Fowler-Taylor A, Cioppa GD, et al. Omalizumab, anti-IgE recombinant humanized monoclonal antibody, for the treatment of severe allergic asthma. J Allergy Clin Immunol. 2001;108(2):184–90.

    Article  PubMed  CAS  Google Scholar 

  34. Buhl R, Soler M, Matz J, Townley R, O’Brien J, Noga O, et al. Omalizumab provides long-term control in patients with moderate-to-severe allergic asthma. Eur Respir J. 2002;20(1):73–8.

    Article  PubMed  CAS  Google Scholar 

  35. Lanier BQ, Corren J, Lumry W, Liu J, Fowler-Taylor A, Gupta N. Omalizumab is effective in the long-term control of severe allergic asthma. Ann Allergy Asthma Immunol. 2003;91(2):154–9.

    Article  PubMed  CAS  Google Scholar 

  36. Niven R, Chung KF, Panahloo Z, Blogg M, Ayre G. Effectiveness of omalizumab in patients with inadequately controlled severe persistent allergic asthma: an open-label study. Respir Med. 2008;102(10):1371–8.

    Article  PubMed  CAS  Google Scholar 

  37. Holgate ST, Chuchalin AG, Hebert J, Lotvall J, Persson GB, Chung KF, et al. Efficacy and safety of a recombinant anti-immunoglobulin E antibody (omalizumab) in severe allergic asthma. Clin Exp Allergy. 2004;34(4):632–8.

    Article  PubMed  CAS  Google Scholar 

  38. 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. 2004;59(7):701–8.

    Article  PubMed  CAS  Google Scholar 

  39. 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(6):1210–6.

    Article  PubMed  CAS  Google Scholar 

  40. Deschildre A, Marguet C, Salleron J, Pin I, Rittie JL, Derelle J, et al. Add-on omalizumab in children with severe allergic asthma: a 1-year real life survey. Eur Respir J. 2013;42(5):1224–33.

    Article  PubMed  CAS  Google Scholar 

  41. Molimard M, Buhl R, Niven R, Le Gros V, Thielen A, Thirlwell J, et al. Omalizumab reduces oral corticosteroid use in patients with severe allergic asthma: real-life data. Respir Med. 2010;104(9):1381–5.

    Article  PubMed  CAS  Google Scholar 

  42. Cazzola M, Camiciottoli G, Bonavia M, Gulotta C, Ravazzi A, Alessandrini A, et al. Italian real-life experience of omalizumab. Respir Med. 2010;104(10):1410–6.

    Article  PubMed  CAS  Google Scholar 

  43. Pelaia G, Gallelli L, Romeo P, Renda T, Busceti MT, Proietto A, et al. Omalizumab decreases exacerbation frequency, oral intake of corticosteroids and peripheral blood eosinophils in atopic patients with uncontrolled asthma. Int J Clin Pharmacol Ther. 2011;49(12):713–21.

    Article  PubMed  CAS  Google Scholar 

  44. Storms W, Bowdish MS, Farrar JR. Omalizumab and asthma control in patients with moderate-to-severe allergic asthma: a 6-year pragmatic data review. Allergy Asthma Proc. 2012;33(2):172–7.

    Article  PubMed  CAS  Google Scholar 

  45. Tzortzaki EG, Georgiou A, Kampas D, Lemessios M, Markatos M, Adamidi T, et al. Long-term omalizumab treatment in severe allergic asthma: the South-Eastern Mediterranean “real-life” experience. Pulm Pharmacol Ther. 2012;25(1):77–82.

    Article  PubMed  CAS  Google Scholar 

  46. Ozgur ES, Ozge C, Ilvan A, Nayci SA. Assessment of long-term omalizumab treatment in patients with severe allergic asthma long-term omalizumab treatment in severe asthma. J Asthma. 2013;50(6):687–94.

    Article  PubMed  Google Scholar 

  47. Domingo C, Moreno A, Jose Amengual M, Monton C, Suarez D, Pomares X. Omalizumab in the management of oral corticosteroid-dependent IGE-mediated asthma patients. Curr Med Res Opin. 2011;27(1):45–53.

    Google Scholar 

  48. Brodlie M, McKean MC, Moss S, Spencer DA. The oral corticosteroid-sparing effect of omalizumab in children with severe asthma. Arch Dis Child. 2012;97(7):604–9.

    Article  PubMed  Google Scholar 

  49. Kumar RK, Herbert C, Kasper M. Reversibility of airway inflammation and remodelling following cessation of antigenic challenge in a model of chronic asthma. Clin Exp Allergy. 2004;34(11):1796–802.

    Article  PubMed  CAS  Google Scholar 

  50. Rabe KF, Calhoun WJ, Smith N, Jimenez P. Can anti-IgE therapy prevent airway remodeling in allergic asthma? Allergy. 2011;66(9):1142–51.

    Article  PubMed  CAS  Google Scholar 

  51. Siergiejko Z, Swiebocka E, Smith N, Peckitt C, Leo J, Peachey G, et al. Oral corticosteroid sparing with omalizumab in severe allergic (IgE-mediated) asthma patients. Curr Med Res Opin. 2011;27(11):2223–8.

    Article  PubMed  CAS  Google Scholar 

  52. Comet R, Domingo C, Larrosa M, Moron A, Rue M, Amengual MJ, 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(3):411–9.

    Article  PubMed  Google Scholar 

  53. Domingo C, Moreno A, Amengual MJ, Comet R, Lujan M. Twelve years’ experience with methotrexate for GINA treatment step 5 asthma patients. Curr Med Res Opin. 2009;25(2):367–74.

    Article  PubMed  CAS  Google Scholar 

  54. Slavin RG, Ferioli C, Tannenbaum SJ, Martin C, Blogg M, Lowe PJ. Asthma symptom re-emergence after omalizumab withdrawal correlates well with increasing IgE and decreasing pharmacokinetic concentrations. J Allergy Clin Immunol. 2009;123(1):107–13.e3.

    Google Scholar 

  55. Nopp A, Johansson SG, Ankerst J, Palmqvist M, Oman H. CD-sens and clinical changes during withdrawal of Xolair after 6 years of treatment. Allergy. 2007;62(10):1175–81.

    Article  PubMed  CAS  Google Scholar 

  56. Nopp A, Johansson SG, Adedoyin J, Ankerst J, Palmqvist M, Oman H. After 6 years with Xolair; a 3-year withdrawal follow-up. Allergy. 2010;65(1):56–60.

    Article  PubMed  CAS  Google Scholar 

  57. Katz R, Rafi A, Do L, Lin M, Mangat R, Azad N, et al. Efficacy of omalizumab using extended dose intervals. J Allergy Clin Immunol. 2007;119(1 (Suppl.):s212.

    Google Scholar 

  58. 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(2):306–20.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  59. Domingo C, Pomares X. Can omalizumab be effective in chronic eosinophilic pneumonia? Chest. 2013;143(1):274.

    Article  PubMed  Google Scholar 

  60. Domingo C, Pomares X, Casabon J, Garcia A, Veigas C, Montón C. Decreasing dose protocol for omalizumab treatment in oral corticosteroid allergic asthma patients. Amsterdam: European Respiratory Society Annual Congress; 2011.

    Google Scholar 

  61. Wenzel SE. Asthma phenotypes: the evolution from clinical to molecular approaches. Nat Med. 2012;18(5):716–25.

    Article  PubMed  CAS  Google Scholar 

  62. Woodruff PG, Boushey HA, Dolganov GM, Barker CS, Yang YH, Donnelly S, 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(40):15858–63.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  63. Woodruff PG, Modrek B, Choy DF, Jia G, Abbas AR, Ellwanger A, et al. T-helper type 2-driven inflammation defines major subphenotypes of asthma. Am J Respir Crit Care Med. 2009;180(5):388–95.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  64. Bhakta NR, Solberg OD, Nguyen CP, Nguyen CN, Arron JR, Fahy JV, et al. A qPCR-based metric of Th2 airway inflammation in asthma. Clin Transl Allergy. 2013; 3(1):24.

    Google Scholar 

  65. Jia G, Erickson RW, Choy DF, Mosesova S, Wu LC, Solberg OD, et al. Periostin is a systemic biomarker of eosinophilic airway inflammation in asthmatic patients. J Allergy Clin Immunol. 2012;130(3):647–54.e10.

    Google Scholar 

  66. Kanemitsu Y, Matsumoto H, Izuhara K, Tohda Y, Kita H, Horiguchi T, et al. Increased periostin associates with greater airflow limitation in patients receiving inhaled corticosteroids. J Allergy Clin Immunol. 2013;132(2):305–12.

    Article  PubMed  CAS  Google Scholar 

  67. 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(8):804–11.

    Article  PubMed  CAS  Google Scholar 

  68. Huggins K, Brostoff J. Local production of specific IgE antibodies in allergic rhinitis patients with negative skin tests. Lancet. 1975;2(7926):148–50.

    Article  PubMed  CAS  Google Scholar 

  69. Carney AS, Powe DG, Huskisson RS, Jones NS. Atypical nasal challenges in patients with idiopathic rhinitis: more evidence for the existence of allergy in the absence of atopy? Clin Exp Allergy. 2002;32(10):1436–40.

    Article  PubMed  CAS  Google Scholar 

  70. Powe DG, Jagger C, Kleinjan A, Carney AS, Jenkins D, Jones NS. ’Entopy’: localized mucosal allergic disease in the absence of systemic responses for atopy. Clin Exp Allergy. 2003;33(10):1374–9.

    Article  PubMed  CAS  Google Scholar 

  71. Rondón C, Romero JJ, López S, Antúnez C, Martín-Casañez E, Torres MJ, et al. Local IgE production and positive nasal provocation test in patients with persistent nonallergic rhinitis. J Allergy Clin Immunol. 2007;119(4):899–905.

    Article  PubMed  Google Scholar 

  72. Wise SK, Ahn CN, Schlosser RJ. Localized immunoglobulin E expression in allergic rhinitis and nasal polyposis. Curr Opin Otolaryngol Head Neck Surg. 2009;17(3):216–22.

    Article  PubMed  Google Scholar 

  73. Vicario M, Blanchard C, Stringer KF, Collins MH, Mingler MK, Ahrens A, et al. Local B cells and IgE production in the oesophageal: mucosa in eosinophilic oesophagitis. Gut. 2010;59(1):12–20.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  74. Humbert M, Menz G, Ying S, Corrigan CJ, Robinson DS, Durham SR, et al. The immunopathology of extrinsic (atopic) and intrinsic (non-atopic) asthma: more similarities than differences. Immunol Today. 1999;20(11):528–33.

    Article  PubMed  CAS  Google Scholar 

  75. Mehlhop PD, Blake K. Impact of inadequately controlled asthma: a need for targeted therapy? J Clin Pharm Ther. 2004;29(3):189–94.

    Article  PubMed  CAS  Google Scholar 

  76. 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 severe, difficult-to-control, nonatopic asthma. Chest. 2013;144(2):411–9.

    Article  PubMed  CAS  Google Scholar 

  77. Owen CE. Immunoglobulin E: role in asthma and allergic disease: lessons from the clinic. Pharmacol Ther. 2007;113(1):121–33.

    Article  PubMed  CAS  Google Scholar 

  78. Vennera M del C, Picado C, Mullol J, Alobid I, Bernal-Sprekelsen M. Efficacy of omalizumab in the treatment of nasal polyps. Thorax. 2011;66(9):824–5.

  79. Gevaert P, Calus L, Van Zele T, Blomme K, De Ruyck N, Bauters W, et al. Omalizumab is effective in allergic and nonallergic patients with nasal polyps and asthma. J Allergy Clin Immunol. 2013;131(1):110–6.e1.

    Google Scholar 

  80. Ying S, Humbert M, Barkans J, Corrigan CJ, Pfister R, Menz G, 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(7):3539–44.

    PubMed  CAS  Google Scholar 

  81. Humbert M, Durham SR, Kimmitt P, Powell N, Assoufi B, Pfister R, 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(5):657–65.

    Article  PubMed  CAS  Google Scholar 

  82. Van Zele T, Gevaert P, Watelet JB, Claeys G, Holtappels G, Claeys C, et al. Staphylococcus aureus colonization and IgE antibody formation to enterotoxins is increased in nasal polyposis. J Allergy Clin Immunol. 2004;114(4):981–3.

    Article  PubMed  Google Scholar 

  83. Zhang N, Gevaert P, van Zele T, Perez-Novo C, Patou J, Holtappels G, et al. An update on the impact of Staphylococcus aureus enterotoxins in chronic sinusitis with nasal polyposis. Rhinology. 2005;43(3):162–8.

    PubMed  CAS  Google Scholar 

  84. Zhang N, Holtappels G, Gevaert P, Patou J, Dhaliwal B, Gould H, et al. Mucosal tissue polyclonal IgE is functional in response to allergen and SEB. Allergy. 2011;66(1):141–8.

    Article  PubMed  Google Scholar 

  85. Domingo C, Pomares X, Angrill N, Rudi N, Amengual M, Mirapeix RM. Effectiveness of omalizumab in non-allergic severe asthma. J Biol Regul Homeost Agents. 2013;27(1):45–53.

    PubMed  CAS  Google Scholar 

  86. Lommatzsch M, Korn S, Buhl R, Virchow JC. Against all odds: anti-IgE for intrinsic asthma? Thorax. 2014;63(1):94–6.

    Article  Google Scholar 

  87. Kalesnikoff J, Huber M, Lam V, Damen JE, Zhang J, Siraganian RP, et al. Monomeric IgE stimulates signaling pathways in mast cells that lead to cytokine production and cell survival. Immunity. 2001;14(6):801–11.

    Article  PubMed  CAS  Google Scholar 

  88. 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 patient with severe asthma and negative skin-prick test results. Chest. 2011;139(1):190–3.

    Article  PubMed  Google Scholar 

  89. Menzella F, Piro R, Facciolongo N, Castagnetti C, Simonazzi A, Zucchi L. Long-term benefits of omalizumab in a patient with severe non-allergic asthma. Allergy Asthma Clin Immunol. 2011;7(1):9.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  90. Perez de Llano L, Vennera Mdel C, Alvarez FJ, Medina JF, Borderias L, Pellicer C, et al. Effects of omalizumab in non-atopic asthma: results from a Spanish multicenter registry. J Asthma. 2013;50(3):296–301.

    Google Scholar 

  91. Stampfli MR, Miescher S, Aebischer I, Zurcher AW, Stadler BM. Inhibition of human IgE synthesis by anti-IgE antibodies requires divalent recognition. Eur J Immunol. 1994;24(9):2161–7.

    Article  PubMed  CAS  Google Scholar 

  92. Davis FM, Gossett LA, Pinkston KL, Liou RS, Sun LK, Kim YW, et al. Can anti-IgE be used to treat allergy? Springer Semin Immunopathol. 1993;15(1):51–73.

    Article  PubMed  CAS  Google Scholar 

  93. Takaku Y, Soma T, Nishihara F, Nakagome K, Kobayashi T, Hagiwara K, et al. Omalizumab attenuates airway inflammation and interleukin-5 production by mononuclear cells in patients with severe allergic asthma. Int Arch Allergy Immunol. 2013;161(Suppl 2):107–17.

    Article  PubMed  CAS  Google Scholar 

  94. Walsh GM. Profile of reslizumab in eosinophilic disease and its potential in the treatment of poorly controlled eosinophilic asthma. Biologics. 2013;7:7–11.

    PubMed Central  PubMed  CAS  Google Scholar 

  95. Domingo X, Bosque M, Valdesoiro L, Larramona H, Vigil L, Maestro A, et al. Induced sputum versus exhaled nitric oxide for the evaluation of airway inflammation in allergic pediatric asthma patients treated with omalizumab. Chest. 2013;144(4_Meeting abstracts):761A.

    Google Scholar 

  96. Parulekar AD, Atik MA, Hanania NA. Periostin, a novel biomarker of Th2-driven asthma. Curr Opin Pulm Med. 2014;20(1):60–5.

    Article  PubMed  CAS  Google Scholar 

  97. 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(1):61–76.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  98. Saini SS, Klion AD, Holland SM, Hamilton RG, Bochner BS, Macglashan DW Jr. The relationship between serum IgE and surface levels of FcεRI on human leukocytes in various diseases: correlation of expression with FcεRI on basophils but not on monocytes or eosinophils. J Allergy Clin Immunol. 2000;106(3):514–20.

    Article  PubMed  CAS  Google Scholar 

  99. Kleine-Tebbe J, Erdmann S, Knol EF, MacGlashan DW Jr, Poulsen LK, Gibbs BF. Diagnostic tests based on human basophils: potentials, pitfalls and perspectives. Int Arch Allergy Immunol. 2006;141(1):79–90.

    Article  PubMed  Google Scholar 

  100. Arm J, Bottoli I, Skerjanec A, Groenewegen A, Lowe P, Maahs S. QGE031 high affinity anti-IgE: tolerability, safety, pharmacokinetics and pharmacodynamics in atopic subjects. European Respiratory Society Annual Congress, Barcelona; 2013 (abstract no. 850518).

  101. Buhl R, Marco AG, Cohen D, Canonica GW. Eligibility for treatment with omalizumab in Italy and Germany. Respir Med. 2014;108(1):50–6.

    Article  PubMed  Google Scholar 

  102. Lafeuille MH, Gravel J, Zhang J, Gorsh B, Figliomeni M, Lefebvre P. Association between consistent omalizumab treatment and asthma control. J Allergy Clin Immunol Pract. 2013;1(1):51–7.

    Article  PubMed  Google Scholar 

Download references

Acknowledgment

The authors thank Michael Maudsley of the University of Barcelona’s Language Service for revising the English.

Declaration of funding

This study was partially funded by grants obtained from the FIS (PI11/02303), FUCAP (Fundació Catalana de Pneumologia 2008) and SEPAR (2009).

Declaration of financial/other relationships

The author declares having received financial support for travel and speakers bureaus from Novartis, Boehringer-Ingelheim, Esteve, Almirall, Chiesi, Menarini, GSK, Takeda, Pfizer, Ferrer, and Astra-Zeneca.

The author also reports that he has no specific conflicts of interest to report regarding this paper.

Author information

Authors and Affiliations

  1. Pulmonary Service, Hospital de Sabadell (Corporació Sanitària i Universitària Parc Taulí), Parc Taulí 1, 08208, Sabadell (Barcelona), Spain

    Christian Domingo

  2. Departament of Medicine, Universitat Autònoma de Barcelona (UAB), Barcelona, Spain

    Christian Domingo

Authors
  1. Christian Domingo
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Christian Domingo.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Domingo, C. Omalizumab for Severe Asthma: Efficacy Beyond the Atopic Patient?. Drugs 74, 521–533 (2014). https://doi.org/10.1007/s40265-014-0203-y

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40265-014-0203-y

Keywords

Search

Navigation