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Omalizumab for Difficult-to-Treat Dermatological Conditions: Clinical and Immunological Features from a Retrospective Real-Life Experience

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Abstract

Background

Omalizumab, a therapeutic monoclonal antibody specific for human IgE, has thus far been used as add-on therapy for moderate-to-severe allergic asthma in adults and children.

Objective

The objective of this study was to test omalizumab efficacy in other conditions in which the IgE-mast cell axis is supposed to play a role.

Methods

Nine patients with dermatological manifestations possibly related to activation of the IgE-mast cell axis (six chronic spontaneous urticaria and three atopic dermatitis patients) were administered off-label omalizumab because of refractoriness to standard therapy. All patients were subjected to strict clinical, laboratoristic, and imaging follow-up to monitor for possible adverse effects. In addition, to further assess the role of omalizumab on T cells, mast cells, and eosinophils, T-cell immune polarisation as well as eosinophil cationic protein and tryptase serum levels were determined before and during omalizumab administration.

Results

Therapy was effective in seven out of nine patients (six complete responses, one partial response, and two no responses). Interestingly, omalizumab appeared to induce lymphocyte polarisation toward a type 2 immune response and to be able to quench eosinophil-mediated inflammation, particularly in atopic dermatitis patients. Tryptase serum levels were generally low and remained unchanged during omalizumab treatment. Despite treatment spanning over several years in most of the patients, no adverse effects nor new ensuing medical conditions have thus far been observed (median follow-up: 42 months).

Conclusions

Off-label omalizumab was safe and effective in our patients. The novel immunologic features recorded in our patients add further complexity to the mechanism of action of omalizumab.

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References

  1. Humbert N, Beasley R, Ayres J, Slavin R, Hébert 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;60:309–16.

    Article  CAS  PubMed  Google Scholar 

  2. Chang TW, Wu PC, Hsu CL, Hung AF. Anti-IgE antibodies for the treatment of IgE-mediated allergic diseases. Adv Immunol. 2007;93:63–119.

    Article  CAS  PubMed  Google Scholar 

  3. Chang TW, Shiung YY. Anti-IgE as a mast cell-stabilizing therapeutic agent. J Allergy Clin Immunol. 2006;117:1203–13.

    Article  CAS  PubMed  Google Scholar 

  4. Brozek JL, Bousquet J, Baena-Cagnani CE, Bonini S, Canonica GW, Casale TB, et al. Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines: 2010 revision. J Allergy Clin Immunol. 2010;126:466–76.

    Article  PubMed  Google Scholar 

  5. 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.

  6. Spector SL, Tan RA. Effect of omalizumab on patients with chronic urticaria. Ann Allergy Asthma Immunol. 2007;99:190–3.

    Article  CAS  PubMed  Google Scholar 

  7. Spector SL, Tan RA. Therapeutic alternatives for chronic urticaria: additional reports on omalizumab. Ann Allergy Asthma Immunol. 2008;101:647.

    Article  PubMed  Google Scholar 

  8. Vestergaard C, Deleuran M. Two cases of severe refractory chronic idiopathic urticaria treated with omalizumab. Acta Derm Venereol. 2010;90:443–4.

    Article  PubMed  Google Scholar 

  9. Romano C, Sellitto A, De Fanis U, Esposito G, Arbo P, Giunta R, Lucivero G. Maintenance of remission with low-dose omalizumab in long-lasting, refractory chronic urticaria. Ann Allergy Asthma Immunol. 2010;104:95–7.

    Article  PubMed  Google Scholar 

  10. Iemoli E, Piconi S, Fusi A, Borgonovo L, Borelli M, Trabattoni D. Immunological effects of omalizumab in chronic urticaria: a case report. J Investig Allergol Clin Immunol. 2010;20:252–4.

  11. 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.

    Article  CAS  PubMed  Google Scholar 

  12. Ferrer M, Gamboa P, Sanz ML, Goikoetxea MJ, Cabrera-Freitag P, Javaloyes G, et al. Omalizumab is effective in nonautoimmune urticaria. J Allergy Clin Immunol. 2011;127:1300–2.

    Article  PubMed  Google Scholar 

  13. Saini S, Rosen KE, Hsieh HJ, Wong DA, Conner E, Kaplan A, et al. A randomized, placebo-controlled, dose-ranging study of single-dose omalizumab in patients with H1-antihistamine-refractory chronic idiopathic urticaria. J Allergy Clin Immunol. 2011;128:567–73.

    Article  CAS  PubMed  Google Scholar 

  14. Maurer M, Altrichter S, Bieber T, Biedermann T, Brautigam M, Seyfried S, et al. Efficacy and safety of omalizumab in patients with chronic urticaria who exhibit IgE against thyroperoxidase. J Allergy Clin Immunol. 2011;128:202–9.

    Article  CAS  PubMed  Google Scholar 

  15. Maurer M, Rosen K, Hsieh HJ, Saini S, Grattan C, Gimenez-Arnau A, et al. Omalizumab for the treatment of chronic idiopathic or spontaneous urticaria. N Engl J Med. 2013;368:924–35.

    Article  CAS  PubMed  Google Scholar 

  16. Kaplan A, Ledford D, Ashby M, Canvin J, Zazzali JL, Conner E, et al. Omalizumab in patients with symptomatic chronic idiopathic/spontaneous urticariadespite standard combination therapy. J Allergy Clin Immunol. 2013;132:101–9.

    Article  CAS  PubMed  Google Scholar 

  17. Saavedra MC, Sur S. Down regulation of the high-affinity IgE receptor associated with successful treatment of chronic idiopathic urticaria with omalizumab. Clin Mol Allergy. 2011;9:2.

    Article  PubMed Central  PubMed  Google Scholar 

  18. Asai K, Kitaura J, Kawakami Y, Yamagata N, Tsai M, Carbone DP, et al. Regulation of mast cell survival by IgE. Immunity. 2001;14:791–800.

    Article  CAS  PubMed  Google Scholar 

  19. 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;14:801–11.

    Article  CAS  PubMed  Google Scholar 

  20. Altrichter S, Peter HJ, Pisarevskaja D, Metz M, Martus P, Maurer M. IgE mediated autoallergy against thyroid peroxidase—a novel pathomechanism of chronic spontaneous urticaria? PLoS One. 2011;6:e14794.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  21. Hatada Y, Kashiwakura J, Hayama K, Fujisawa D, Sasaki-Sakamoto T, Terui T, et al. Significantly high levels of anti-dsDNA immunoglobulin E in sera and the ability of dsDNA to induce the degranulation of basophils from chronic urticaria patients. Int Arch Allergy Immunol. 2013;161(suppl 2):154–8.

    Article  CAS  PubMed  Google Scholar 

  22. Chang TW, Chen C, Lin C-J, Metz M, Church MK, Maurer M. The potential pharmacologic mechanisms of omalizumab in patients with chronic spontaneous urticaria. J Allergy Clin Immunol. 2014. doi:10.1016/j.jaci.2014.04.036.

    PubMed Central  Google Scholar 

  23. Morjaria JB, Polosa R. Off-label use of omalizumab in non-asthma conditions: new opportunities. Expert Rev Respir Med. 2009;3:299–308.

    Article  CAS  PubMed  Google Scholar 

  24. Incorvaia C, Mauro M, Russello M, Formigoni C, Riario-Sforza GG, Ridolo E. Omalizumab, an anti-immunoglobulin E antibody: state of the art. Drug Des Devel Ther. 2014;8:197–207.

  25. Zuberbier T, Aberer W, Asero R, Bindslev-Jensen C, Brzoza Z, Canonica GW, et al. The EAACI/GA(2) LEN/EDF/WAO guideline for the definition, classification, diagnosis, and management of urticaria: the 2013 revision and update. Allergy. 2014;69:868–87.

    Article  CAS  PubMed  Google Scholar 

  26. Eichenfield LF, Tom WL, Chamlin SL, Feldman SR, Hanifin JM, Simpson EL, et al. Guidelines of care for the management of atopic dermatitis: section 1. Diagnosis and assessment of atopic dermatitis. J Am Acad Dermatol. 2014;70:338–51.

  27. Jáuregui I, Ortiz de Frutos FJ, Ferrer M, Giménez-Arnau A, Sastre J, Bartra J, et al. Assessment of severity and quality of life in chronic urticaria. J Investig Allergol Clin Immunol. 2014;24:80–6.

  28. Romano C, De Fanis U, Sellitto A, Chiurazzi F, Guastafierro S, Giunta R, et al. Induction of CD95 upregulation does not render chronic lymphocytic leukemia B-cells susceptible to CD95-mediated apoptosis. Immunol Lett. 2005;97:131–9.

    Article  CAS  PubMed  Google Scholar 

  29. Sellitto A, Galizia G, De Fanis U, Lieto E, Zamboli A, Orditura M, et al. Behavior of circulating CD4+CD25+Foxp3+ regulatory T cells in colon cancer patients undergoing surgery. J Clin Immunol. 2011;31:1095–104.

    Article  CAS  PubMed  Google Scholar 

  30. Loetscher P, Uguccioni M, Bordoli L, Baggiolini M, Moser B, Chizzolini C, et al. CCR5 is characteristic of Th1 lymphocytes. Nature. 1998;391:344–5.

    Article  CAS  PubMed  Google Scholar 

  31. Qin S, Rottman JB, Myers P, Kassam N, Weinblatt M, Loetscher M, et al. The chemokine receptors CXCR3 and CCR5 mark subsets of T cells associated with certain inflammatory reactions. J Clin Invest. 1998;101:746–54.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  32. Nagata K, Tanaka K, Ogawa K, Kemmotsu K, Imai T, Yoshie O, et al. Selective expression of a novel surface molecule by human Th2 cells in vivo. J Immunol. 1999;162:1278–86.

    CAS  PubMed  Google Scholar 

  33. Cosmi L, Annunziato F, Iwasaki M, Galli G, Manetti R, Maggi E, et al. CRTH2 is the most reliable marker for the detection of circulating human type 2 Th and type 2 T cytotoxic cells in health and disease. Eur J Immunol. 2000;30:2972–9.

    Article  CAS  PubMed  Google Scholar 

  34. De Fanis U, Mori F, Kurnat RJ, Lee WK, Bova M, Adkinson NF, et al. GATA3 up-regulation associated with surface expression of CD294/CRTH2: a unique feature of human Th cells. Blood. 2007;109:4343–50.

    Article  PubMed Central  PubMed  Google Scholar 

  35. Boin F, De Fanis U, Bartlett SJ, Wigley FM, Rosen A, Casolaro V. T cell polarization identifies distinct clinical phenotypes in scleroderma lung disease. Arthritis Rheum. 2008;58:1165–74.

    Article  PubMed Central  PubMed  Google Scholar 

  36. De Fanis U, Wang GC, Fedarko NS, Walston JD, Casolaro V, Leng SX. T-lymphocytes expressing CC chemokine receptor-5 are increased in frail older adults. J Am Geriatr Soc. 2008;56:904–8.

    Article  PubMed Central  PubMed  Google Scholar 

  37. Onoé K, Yanagawa Y, Minami K, Iijima N, Iwabuchi K. Th1 or Th2 balance regulated by interaction between dendritic cells and NKT cells. Immunol Res. 2007;38:319–32.

    Article  PubMed  Google Scholar 

  38. Iyengar SR, Hoyte EG, Loza A, Bonaccorso S, Chiang D, Umetsu DT, Nadeau KC. Immunologic effects of omalizumab in children with severe refractory atopic dermatitis: a randomized, placebo-controlled clinical trial. Int Arch Allergy Immunol. 2013;162:89–93.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  39. Baker BS. The role of microorganisms in atopic dermatitis. Clin Exp Immunol. 2006;144:1–9.

  40. Furuta GT, Atkins FD, Lee NA, Lee JJ. Changing roles of eosinophils in health and disease. Ann Allergy Asthma Immunol. 2014;113:3–8.

    Article  CAS  PubMed  Google Scholar 

  41. 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;170:583–93.

    Article  PubMed  Google Scholar 

  42. Riccio AM, Dal Negro RW, Micheletto C, De Ferrari L, Folli C, Chiappori A, Canonica GW. Omalizumab modulates bronchial reticular basement membrane thickness and eosinophil infiltration in severe persistent allergic asthma patients. Int J Immunopathol Pharmacol. 2012;25:475–84.

  43. Asero R, Cugno M, Tedeschi A. Eosinophils in chronic urticaria: supporting or leading actors? World Allergy Organ J. 2009;2:213–7.

    Article  PubMed Central  PubMed  Google Scholar 

  44. Schwartz LB. Diagnostic value of tryptase in anaphylaxis and mastocytosis. Immunol Allergy Clin North Am. 2006;26:451–63.

    Article  PubMed  Google Scholar 

  45. Delong LK, Culler SD, Saini SS, Beck LA, Chen SC. Annual direct and indirect health care costs of chronic idiopathic urticaria: a cost analysis of 50 nonimmunosuppressed patients. Arch Dermatol. 2008;144:35–9.

    Article  PubMed  Google Scholar 

  46. Fowler JF, Duh MS, Rovba L, Buteau S, Pinheiro L, Lobo F, et al. The direct and indirect cost burden of atopic dermatitis: an employer-payer perspective. Manag Care Interface. 2007;20:26–32.

    PubMed  Google Scholar 

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Conflict of interest

No sources of funding were used for the conduct of this study. The authors declare that they have no conflict of interest.

Author information

Author notes

  1. Ausilia Sellitto

    Present address: “San Giuseppe Moscati” Hospital, Aversa, CE, Italy

  2. Umberto De Fanis

    Present address: Clinic Center, Naples, Italy

Authors and Affiliations

  1. Division of Internal Medicine, Allergy and Clinical Immunology, Department of Medical and Surgical Sciences, Second University of Naples School of Medicine, 80138, Naples, Italy

    Ciro Romano, Ausilia Sellitto, Umberto De Fanis & Giacomo Lucivero

  2. Allergy Clinic, “F. Magrassi-A. Lanzara” Department of Clinical and Experimental Medicine and Surgery, Second University of Naples, Naples, Italy

    Antonella Balestrieri, Alfonso Savoia & Corrado Astarita

  3. Immunopathology Unit, Department of Laboratory Medicine, Second University of Naples, Naples, Italy

    Salvatore Abbadessa

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  1. Ciro Romano
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Correspondence to Ciro Romano.

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Romano, C., Sellitto, A., De Fanis, U. et al. Omalizumab for Difficult-to-Treat Dermatological Conditions: Clinical and Immunological Features from a Retrospective Real-Life Experience. Clin Drug Investig 35, 159–168 (2015). https://doi.org/10.1007/s40261-015-0267-9

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  • DOI: https://doi.org/10.1007/s40261-015-0267-9

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