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Targeting immunoglobulin E as a novel treatment for asthma

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Abstract

Omalizumab is a recently developed monoclonal anti-IgE antibody. Clinical trials have demonstrated its efficacy in patients with moderate-to-severe and severe or poorly controlled allergic asthma, in patients with seasonal and perennial allergic disease, and in subjects with concomitant asthma and allergic rhinitis. Patients with more severe asthma appear to obtain the greatest benefit from omalizumab therapy. Omalizumab is well tolerated and has a good safety profile. Anti-inflammatory activity has been shown in both allergic asthma and allergic rhinitis. These results confirm the importance of IgE in allergic disease and support the rationale behind the development of a therapeutic anti-IgE antibody. Omalizumab is a significant addition to current asthma treatments and shows great promise as a therapy for allergic rhinitis, in particular for those patients with concomitant allergic disease.

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References and Recommended Reading

  1. Burney P: The changing prevalence of asthma? Thorax 2002, 57(Suppl 2):II36-II39.

    PubMed  Google Scholar 

  2. Sporik R, Platts-Mills TA: Allergen exposure and the development of asthma. Thorax 2001, 56(Suppl 2):ii58-ii63.

    PubMed  Google Scholar 

  3. Court CS, Cook DG, Strachan DP: Comparative epidemiology of atopic and non-atopic wheeze and diagnosed asthma in a national sample of English adults. Thorax 2002, 57(11):951–957.

    Article  PubMed  CAS  Google Scholar 

  4. Jackola DR, Blumenthal MN, Rosenberg A: Evidence for two independent distributions of serum immunoglobulin E in atopic families: cognate and non-cognate IgE. Hum Immunol 2004, 65:20–30.

    Article  PubMed  CAS  Google Scholar 

  5. MacGlashan DW Jr, Bochner BS, Adelman DC, et al.: Downregulation of Fc(epsilon)RI expression on human basophils during in vivo treatment of atopic patients with anti-IgE antibody. J Immunol 1997, 158:1438–1445.

    PubMed  CAS  Google Scholar 

  6. Foster B, Metcalfe DD, Prussin C: Human dendritic cell 1 and dendritic cell 2 subsets express FcepsilonRI: correlation with serum IgE and allergic asthma. J Allergy Clin Immunol 2003, 112:1132–1138.

    Article  PubMed  CAS  Google Scholar 

  7. Bousquet J, Van Cauwenberge P, Khaltaev N: Allergic rhinitis and its impact on asthma. ARIA Workshop Group; World Health Organization. J Allergy Clin Immunol 2001, (1085 Suppl):S147–S334.

  8. Bousquet J, Vignola AM, Demoly P: Links between rhinitis and asthma. Allergy 2003, 58:691–706.

    Article  PubMed  CAS  Google Scholar 

  9. Leynaert B, Neukirch C, Kony S, et al.: Association between asthma and rhinitis according to atopic sensitization in a population-based study. J Allergy Clin Immunol 2004, 113:86–93.

    Article  PubMed  Google Scholar 

  10. Presta LG, Lahr SJ, Shields RL, et al.: Humanization of an antibody directed against IgE. J Immunol 1993, 151:2623–2632.

    PubMed  CAS  Google Scholar 

  11. Presta L, Shields R, O’Connell L, et al.: The binding site on human immunoglobulin E for its high affinity receptor. J Biol Chem 1994, 269:26368–26373.

    PubMed  CAS  Google Scholar 

  12. Shields RL, Whether WR, Zioncheck K, et al.: Inhibition of allergic reactions with antibodies to IgE. Int Arch Allergy Immunol 1995, 107:308–312.

    PubMed  CAS  Google Scholar 

  13. Liu J, Lester P, Builder S, Shire SJ: Characterization of complex formation by humanized anti-IgE monoclonal antibody and monoclonal human IgE. Biochemistry 1995, 34:10474–10482.

    Article  PubMed  CAS  Google Scholar 

  14. MacGlashan DW Jr, Bochner BS, Adelman DC, et al.: Serum IgE level drives basophil and mast cell IgE receptor display. Int Arch Allergy Immunol 1997, 113:45–47.

    Article  PubMed  CAS  Google Scholar 

  15. Lin H, Boesel KM, Griffith DT, et al.: Omalizumab rapidly decreases nasal allergic response and FcepsilonRI on basophils. J Allergy Clin Immunol 2004, 113:297–302.

    Article  PubMed  CAS  Google Scholar 

  16. Boulet LP, Chapman KR, Cote J, et al.: Inhibitory effects of an anti-IgE antibody E25 on allergen-induced early asthmatic response. Am J Respir Crit Care Med 1997, 155:1835–1840.

    PubMed  CAS  Google Scholar 

  17. Fahy JV, Fleming HE, Wong HH, et al.: The effect of an anti-IgE monoclonal antibody on the early- and late-phase responses to allergen inhalation in asthmatic subjects. Am J Respir Crit Care Med 1997, 155:1828–1834.

    PubMed  CAS  Google Scholar 

  18. Casale TB, Bernstein IL, Busse WW, et al.: Use of an anti-IgE humanized monoclonal antibody in ragweed-induced allergic rhinitis. J Allergy Clin Immunol 1997, 100:110–121.

    Article  PubMed  CAS  Google Scholar 

  19. Casale TB, Condemi J, LaForce C, et al.: Effect of omalizumab on symptoms of seasonal allergic rhinitis: a randomized controlled trial. JAMA 2001, 286:2956–2967.

    Article  PubMed  CAS  Google Scholar 

  20. Hochhaus G, Brookman L, Fox H, et al.: Pharmacodynamics of omalizumab: implications for optimised dosing strategies and clinical efficacy in the treatment of allergic asthma. Curr Med Res Opin 2003, 19:491–498. This paper provides a useful explanation of the dosing regimen for omalizumab.

    Article  PubMed  CAS  Google Scholar 

  21. Busse W, Corren J, Lanier BQ, et al.: Omalizumab, anti-IgE recombinant humanized monoclonal antibody, for the treatment of severe allergic asthma. J Allergy Clin Immunol 2001, 108:184–190.

    Article  PubMed  CAS  Google Scholar 

  22. Soler M, Matz J, Townley R, et al.: The anti-IgE antibody omalizumab reduces exacerbations and steroid requirement in allergic asthmatics. Eur Respir J 2001, 18:254–261.

    Article  PubMed  CAS  Google Scholar 

  23. Milgrom H, Berger W, Nayak A, et al.: Treatment of childhood asthma with anti-immunoglobulin E antibody (omalizumab). Pediatrics 2001, 108:E36.

    Article  PubMed  CAS  Google Scholar 

  24. Finn A, Gross G, van Bavel J, et al.: Omalizumab improves asthma-related quality of life in patients with severe allergic asthma. J Allergy Clin Immunol 2003, 111:278–284.

    Article  PubMed  CAS  Google Scholar 

  25. Buhl R, Hanf G, Soler M, et al.: The anti-IgE antibody omalizumab improves asthma-related quality of life in patients with allergic asthma. Eur Respir J 2002, 20:1088–1094.

    Article  PubMed  CAS  Google Scholar 

  26. Lemanske RF Jr, Nayak A, McAlary M, et al.: Omalizumab improves asthma-related quality of life in children with allergic asthma. Pediatrics 2002, 110:e55.

    Article  PubMed  Google Scholar 

  27. 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. Omalizumab reduced serious asthma exacerbations in a large population and had a particularly marked effect on attacks leading to hospitalization. This may have important implications for preventing asthma-related deaths.

    Article  PubMed  CAS  Google Scholar 

  28. Crane J, Pearce N, Burgess C, et al.: Markers of risk of asthma death or readmission in the 12 months following a hospital admission for asthma. Int J Epidemiol 1992, 21:737–744.

    Article  PubMed  CAS  Google Scholar 

  29. Smith DH, Malone DC, Lawson KA, et al.: A national estimate of the economic costs of asthma. Am J Respir Crit Care Med 1997, 156(3 Pt 1):787–793.

    PubMed  CAS  Google Scholar 

  30. Holgate ST, Chuchalin AG, Hébert J, et al.: Efficacy and safety of a recombinant anti-IgE antibody (omalizumab) in severe allergic asthma. Clin Exp Allergy 2004, 34:632–638. The demonstration of improved asthma control and reduced inhaled corticosteroid requirements is notable in a group of patients with severe asthma.

    Article  PubMed  CAS  Google Scholar 

  31. Frew AJ: Anti-IgE and asthma. Ann Allergy Asthma Immunol 2003, 91:117–118.

    PubMed  Google Scholar 

  32. Bousquet J, Wenzel S, Holgate S, et al.: Predicting response to omalizumab, an anti-immunoglobulin E antibody, in patients with allergic asthma. Chest 2004, 125:1378–1386. The results of this analysis are helpful to the practicing chest physician in deciding which patients should receive omalizumab. The study shows the greatest benefit of treatment in patients with the most severe asthma at baseline.

    Article  PubMed  CAS  Google Scholar 

  33. Holgate S, Bousquet J, Wenzel S, et al.: 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, 17:233–240.

    Article  PubMed  CAS  Google Scholar 

  34. Ayres JG, Higgins B, Chilvers ER, et al.: Efficacy and tolerability of anti-immunoglobulin E therapy with omalizumab in patients with poorly controlled (moderate-to-severe) allergic asthma. Allergy 2004, 59:701–708. Although this was an open-label study, the results indicated the benefits that may be expected from omalizumab therapy in a group of asthma patients who were poorly controlled despite receiving high doses of inhaled corticosteroids and, in many cases, oral steroids—a group for whom very few therapeutic options are available.

    Article  PubMed  CAS  Google Scholar 

  35. Global Initiative for Asthma (GINA): Global strategy for asthma management and prevention. NIH publication 02-3659 issued January 1995 (updated 2002, 2003). At: www.ginasthma.com. Accessed April 26, 2004.

  36. Bousquet J, Ayre G, Blogg M: Omalizumab added to best standard care reduces exacerbations in patients with severe persistent asthma according to GINA 2002 classification (abstract). ERS 2004.

  37. Ädelroth E, Rak S, Haahtela T, et al.: Recombinant humanized mAb-E25, an anti-IgE mAb, in birch pollen-induced seasonal allergic rhinitis. J Allergy Clin Immunol 2000, 106:253–259.

    Article  PubMed  Google Scholar 

  38. Chervinsky P, Casale T, Townley R, et al.: Omalizumab, an anti-IgE antibody, in the treatment of adults and adolescents with perennial allergic rhinitis. Ann Allergy Asthma Immunol 2003, 91:160–167.

    PubMed  CAS  Google Scholar 

  39. Vignola AM, Humbert M, Bousquet J, et al.: Efficacy and tolerability of anti-immunoglobulin E therapy with omalizumab in patients with concomitant allergic asthma and persistent allergic rhinitis: SOLAR. Allergy 2004, 59:709–717. Omalizumab was effective in preventing asthma exacerbations and improving quality of life in patients with comorbid allergic diseases. It is expected that omalizumab, as a systemically administered anti-IgE agent, would benefit patients with multiple manifestations of allergic disease.

    Article  PubMed  CAS  Google Scholar 

  40. Sussman G: Lessons learned from latex allergy. Ann Allergy Asthma Immunol 2003, 91:510–511.

    PubMed  Google Scholar 

  41. Leynadier F, Doudou O, Gaouar H, et al.: Effect of omalizumab in health care workers with occupational latex allergy. J Allergy Clin Immunol 2004, 113:360–361.

    Article  PubMed  CAS  Google Scholar 

  42. Leung DY, Shanahan WR Jr, Sampson HA: Response to "effect of anti-IgE therapy in patients with food allergy". Ann Allergy Asthma Immunol 2003, 91:515–517.

    PubMed  CAS  Google Scholar 

  43. Leung DY, Sampson HA, Yunginger JW, et al.: Effect of anti-IgE therapy in patients with peanut allergy. N Engl J Med 2003, 348:986–993.

    Article  PubMed  CAS  Google Scholar 

  44. Djukanovi R, Wilson SJ, Kraft M, et al.: The effects of anti-IgE (omalizumab) treatment on airways inflammation in allergic asthma. Am J Respir Crit Care Med 2004, 170:583–593. This is the first demonstration of the anti-inflammatory effects of anti-IgE therapy with omalizumab. Eosinophils (sputum and mucosal tissue) were reduced by an extent similar to that observed with corticosteroids. The reduction in lung tissue IgE+ cells confirms effects previously observed on circulating basophils.

    Article  Google Scholar 

  45. Plewako H, Arvidsson M, Petruson K, et al.: The effect of omalizumab on nasal allergic inflammation. J Allergy Clin Immunol 2002, 110:68–71. A demonstration of anti-inflammatory effects on circulating and nasal tissue eosinophils.

    Article  PubMed  CAS  Google Scholar 

  46. Prussin C, Griffith DT, Boesel KM, et al.: Omalizumab treatment downregulates dendritic cell FcepsilonRI expression. J Allergy Clin Immunol 2003, 112:1147–1154. The therapeutic downregulation of IgE receptors on circulating precursor dendritic cells suggests that omalizumab may act to inhibit both sensitization and effector phases of the allergen-specific immune response.

    Article  PubMed  CAS  Google Scholar 

  47. US Food and Drug Administration: Briefing document on safety. Omalizumab (Xolair) (recombinant humanized monoclonal antibody to IgE) for treatment of allergic asthma. http:/ /www.fda.gov/ohrms/dockets/ac/03/briefing/3952B1_02_FDAXolair-Safety.pdf.April 18, 2003. Accessed 29 March 2004.

  48. Ries LAG, Eisner MP, Kosary CL, et al. (Eds). SEER Cancer Statistics Review, National Cancer Institute. Bethesda, MD. http://seer.cancer.gov/csr/1975_2000, 2003.1975-2000,

  49. Lanier BQ, Corren J, Lumry W, et al.: Omalizumab is effective in the long-term control of severe allergic asthma. Ann Allergy Asthma Immunol 2003, 91:154–159.

    PubMed  CAS  Google Scholar 

  50. Buhl R, Soler M, Matz J, et al.: Omalizumab provides longterm control in patients with moderate-to-severe allergic asthma. Eur Respir J 2002, 20:73–78.

    Article  PubMed  CAS  Google Scholar 

  51. Berger W, Gupta N, McAlary M, Fowler-Taylor A: Evaluation of long-term safety of the anti-IgE antibody, omalizumab, in children with allergic asthma. Ann Allergy Asthma Immunol 2003, 91:182–188.

    Article  PubMed  CAS  Google Scholar 

  52. Nayak A, Casale T, Miller SD, et al.: Tolerability of retreatment with omalizumab, a recombinant humanized monoclonal anti-IgE antibody, during a second ragweed pollen season in patients with seasonal allergic rhinitis. Allergy Asthma Proc 2003, 24:323–329. An important safety study to investigate the possible development of anti-omalizumab antibodies on re-treatment.

    PubMed  CAS  Google Scholar 

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  1. Department of Respiratory Medicine & Allergy, University Hospital, SE-901 85, Umeå, Sweden

    Thomas Sandström MD, PhD

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  1. Thomas Sandström MD, PhD
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Sandström, T. Targeting immunoglobulin E as a novel treatment for asthma. Curr Allergy Asthma Rep 5, 109–115 (2005). https://doi.org/10.1007/s11882-005-0083-z

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