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Current Treatment Options in Allergy

, Volume 6, Issue 3, pp 175–188 | Cite as

Treatment of Chronic Spontaneous Urticaria: a Focused Update in Omalizumab

  • Whitney A. BlackwellEmail author
  • David A. Khan
Urticaria and Atopic Dermatitis (M Furue and T Nakahara, Section Editors)
  • 23 Downloads
Part of the following topical collections:
  1. Topical Collection on Urticaria and Atopic Dermatitis

Abstract

Purpose of review

Chronic spontaneous urticaria (CSU) is a common disease in the general population that causes significant effects on quality of life and a financial burden on the health care system. Guidelines are essential to assure patients are being managed appropriately, although given the rigor to develop these reviews they are not as up to date as cutting-edge scientific evidence. This review details the most recent phase II, III, and IV clinical trials that have been published since the development of the US practice parameters.

Recent findings

Phase II, III, and IV clinical trials, ASTERIA I, POLARIS, X-ACT, MoA, and CTEND-CIU, demonstrate safety, long-term efficacy, and improvement in patient’s quality of life by decreasing disease-burdened days and severity of disease in comparison with placebo, as well as transcriptional level changes in gene expression with omalizumab use. Data is emerging regarding efficacy in inducible urticarias, predictors of response, and optimal methods for discontinuation of omalizumab.

Summary

Optimal treatment of CSU should be based on recent practice parameters and guidelines. Recent evidence supports the use of omalizumab in antihistamine refractory urticaria patients, but the mechanism for its effect, identification of biomarkers to predict response to therapy, optimal duration, and adjustments in dosing all require additional investigation.

Keywords

Omalizumab Urticaria Treatment Adverse effect Angioedema 

Notes

Compliance with Ethical Standards

Conflict of Interest

Whitney A. Blackwell declares that she has no conflict of interest.

David A. Khan declares that he has no conflict of interest.

Human and Nnimal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Bailey E, Shaker M. An update on childhood urticaria and angioedema. Curr Opin Pediatr. 2008;20(4):425–30.PubMedGoogle Scholar
  2. 2.
    Yates C. Parameters for the treatment of urticaria and angioedema. J Am Acad Nurse Pract. 2002;14(11):478–83.PubMedGoogle Scholar
  3. 3.
    Bernstein JA, Lang DM, Khan DA, Craig T, Dreyfus D, Hsieh F, et al. The diagnosis and management of acute and chronic urticaria: 2014 update. J Allergy Clin Immunol. 2014;133(5):1270–7.PubMedGoogle Scholar
  4. 4.
    van der Valk PG, Moret G, Kiemeney LA. The natural history of chronic urticaria and angioedema in patients visiting a tertiary referral Centre. Br J Dermatol. 2002;146(1):110–3.PubMedGoogle Scholar
  5. 5.
    Sanchez-Borges M, Caballero-Fonseca F, Capriles-Hulett A, Gonzalez-Aveledo L, Maurer M. Factors linked to disease severity and time to remission in patients with chronic spontaneous urticaria. J Eur Acad Dermatol Venereol. 2017;31(6):964–71.PubMedGoogle Scholar
  6. 6.
    Lee SJ, Ha EK, Jee HM, Lee KS, Lee SW, Kim MA, et al. Prevalence and risk factors of urticaria with a focus on chronic urticaria in children. Allergy, Asthma Immunol Res. 2017;9(3):212–9.Google Scholar
  7. 7.
    Gaig P, Olona M, Munoz Lejarazu D, Caballero MT, Dominguez FJ, Echechipia S, et al. Epidemiology of urticaria in Spain. J Investig Allergol Clin Immunol. 2004;14(3):214–20.PubMedGoogle Scholar
  8. 8.
    •• Zuberbier T, Aberer W, Asero R, Abdul Latiff AH, Baker D, Ballmer-Weber B, et al. The EAACI/GA(2)LEN/EDF/WAO guideline for the definition, classification, diagnosis and management of urticaria. Allergy. 2018;73(7):1393–414 The most recent international guidelines for definition, classification, diagnosis, and treatment of urticaria.PubMedGoogle Scholar
  9. 9.
    • Wood RA, Khan DA, Lang DM, Fasano MB, Peden DB, Busse PJ, et al. American Academy of allergy, asthma and immunology response to the EAACI/GA(2) LEN/EDF/WAO guideline for the definition, classification, diagnosis, and management of Urticaria 2017 revision. Allergy. 2019;74(2):411–3 This is reviews the AAAAI’s response to the changes made to the international guidelines.PubMedGoogle Scholar
  10. 10.
    Lutfeali S, Khan DA. Review and perspectives of the recent international guidelines on treatment of chronic urticaria. Curr Treat Options Allergy. 2018;5(4):392–404.Google Scholar
  11. 11.
    Maurer M, Abuzakouk M, Berard F, Canonica W, Oude Elberink H, Gimenez-Arnau A, et al. The burden of chronic spontaneous urticaria is substantial: real-world evidence from ASSURE-CSU. Allergy. 2017;72(12):2005–16.PubMedPubMedCentralGoogle Scholar
  12. 12.
    Weller K, Groffik A, Church MK, Hawro T, Krause K, Metz M, et al. Development and validation of the Urticaria Control Test: a patient-reported outcome instrument for assessing urticaria control. J Allergy Clin Immunol. 2014;133(5):1365–72 72 e1-6.Google Scholar
  13. 13.
    Baiardini I, Pasquali M, Braido F, Fumagalli F, Guerra L, Compalati E, et al. A new tool to evaluate the impact of chronic urticaria on quality of life: chronic urticaria quality of life questionnaire (CU-QoL). Allergy. 2005;60(8):1073–8.PubMedGoogle Scholar
  14. 14.
    Ohanyan T, Schoepke N, Bolukbasi B, Metz M, Hawro T, Zuberbier T, et al. Responsiveness and minimal important difference of the urticaria control test. J Allergy Clin Immunol. 2017;140(6):1710–3 e11.PubMedGoogle Scholar
  15. 15.
    Baiardini I, Braido F, Molinengo G, Caminati M, Costantino M, Cristaudo A, et al. Chronic Urticaria Patient Perspective (CUPP): the first validated tool for assessing quality of life in clinical practice. J Allergy Clin Immunol Pract. 2018;6(1):208–18.PubMedGoogle Scholar
  16. 16.
    Balp MM, Weller K, Carboni V, Chirilov A, Papavassilis C, Severin T, et al. Prevalence and clinical characteristics of chronic spontaneous urticaria in pediatric patients. Pediatr Allergy Immunol. 2018;29(6):630–6.PubMedGoogle Scholar
  17. 17.
    Guillen-Aguinaga S, Jauregui Presa I, Aguinaga-Ontoso E, Guillen-Grima F, Ferrer M. Updosing nonsedating antihistamines in patients with chronic spontaneous urticaria: a systematic review and meta-analysis. Br J Dermatol. 2016;175(6):1153–65.PubMedGoogle Scholar
  18. 18.
    Staevska M, Gugutkova M, Lazarova C, Kralimarkova T, Dimitrov V, Zuberbier T, et al. Night-time sedating H1 -antihistamine increases daytime somnolence but not treatment efficacy in chronic spontaneous urticaria: a randomized controlled trial. Br J Dermatol. 2014;171(1):148–54.PubMedPubMedCentralGoogle Scholar
  19. 19.
    Simons FE, Simons KJ, Frith EM. The pharmacokinetics and antihistaminic of the H1 receptor antagonist hydroxyzine. J Allergy Clin Immunol. 1984;73(1 Pt 1):69–75.PubMedGoogle Scholar
  20. 20.
    Gray SL, Anderson ML, Dublin S, Hanlon JT, Hubbard R, Walker R, et al. Cumulative use of strong anticholinergics and incident dementia: a prospective cohort study. JAMA Intern Med. 2015;175(3):401–7.PubMedPubMedCentralGoogle Scholar
  21. 21.
    Gray SL, Anderson ML, Hanlon JT, Dublin S, Walker RL, Hubbard RA, et al. Exposure to strong anticholinergic medications and dementia-related neuropathology in a community-based autopsy cohort. J Alzheimers Dis. 2018;65(2):607–16.PubMedPubMedCentralGoogle Scholar
  22. 22.
    Weller K, Schoepke N, Krause K, Ardelean E, Brautigam M, Maurer M. Selected urticaria patients benefit from a referral to tertiary care centres--results of an expert survey. J Eur Acad Dermatol Venereol. 2013;27(1):e8–16.PubMedGoogle Scholar
  23. 23.
    Morgan M, Khan DA. Therapeutic alternatives for chronic urticaria: an evidence-based review, part 2. Ann Allergy Asthma Immunol. 2008;100(6):517–26 quiz 26-8, 44.Google Scholar
  24. 24.
    Morgan M, Khan DA. Therapeutic alternatives for chronic urticaria: an evidence-based review, part 1. Ann Allergy Asthma Immunol. 2008;100(5):403–11 quiz 12-4, 68.Google Scholar
  25. 25.
    Khan DA. Alternative agents in refractory chronic urticaria: evidence and considerations on their selection and use. J Allergy Clin Immunol Pract. 2013;1(5):433–40 e1.PubMedGoogle Scholar
  26. 26.
    Chang TW, Chen C, Lin CJ, Metz M, Church MK, Maurer M. The potential pharmacologic mechanisms of omalizumab in patients with chronic spontaneous urticaria. J Allergy Clin Immunol. 2015;135(2):337–42.PubMedGoogle Scholar
  27. 27.
    Maurer M, Vena GA, Cassano N, Zuberbier T. Current and future therapies for treating chronic spontaneous urticaria. Expert Opin Pharmacother. 2016;17(8):1131–9.PubMedGoogle Scholar
  28. 28.
    Kaplan AP, Gimenez-Arnau AM, Saini SS. Mechanisms of action that contribute to efficacy of omalizumab in chronic spontaneous urticaria. Allergy. 2017;72(4):519–33.PubMedPubMedCentralGoogle Scholar
  29. 29.
    Schmetzer O, Lakin E, Topal FA, Preusse P, Freier D, Church MK, et al. IL-24 is a common and specific autoantigen of IgE in patients with chronic spontaneous urticaria. J Allergy Clin Immunol. 2018;142(3):876–82.PubMedGoogle Scholar
  30. 30.
    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(1):202–9 e5.PubMedGoogle Scholar
  31. 31.
    Schulman ES. Development of a monoclonal anti-immunoglobulin E antibody (omalizumab) for the treatment of allergic respiratory disorders. Am J Respir Crit Care Med. 2001;164(8 Pt 2):S6–11.PubMedGoogle Scholar
  32. 32.
    Xolair. Prescribing information. 2015 [Available from: http://www.gene.com/download/pdf/xolair_prescribing.pdf. Accessed 1 May 2019.
  33. 33.
    Kaplan AP, Joseph K, Maykut RJ, Geba GP, Zeldin RK. Treatment of chronic autoimmune urticaria with omalizumab. J Allergy Clin Immunol. 2008;122(3):569–73.PubMedGoogle Scholar
  34. 34.
    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(5):1300–2.PubMedGoogle Scholar
  35. 35.
    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(3):567–73 e1.Google Scholar
  36. 36.
    Gober L, Sterba P, Eckman J. Effect of anti-IgE (Omalizumab) in chronic idiopathic urticaria (CIU) patients. J Allergy Clin Immunol. 2008;121(2):S147.Google Scholar
  37. 37.
    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(10):924–35.PubMedGoogle Scholar
  38. 38.
    Kaplan A, Ledford D, Ashby M, Canvin J, Zazzali JL, Conner E, et al. Omalizumab in patients with symptomatic chronic idiopathic/spontaneous urticaria despite standard combination therapy. J Allergy Clin Immunol. 2013;132(1):101–9.PubMedGoogle Scholar
  39. 39.
    Saini SS, Bindslev-Jensen C, Maurer M, Grob JJ, Bulbul Baskan E, Bradley MS, et al. Efficacy and safety of omalizumab in patients with chronic idiopathic/spontaneous urticaria who remain symptomatic on H1 antihistamines: a randomized, placebo-controlled study. J Invest Dermatol. 2015;135(1):67–75.PubMedGoogle Scholar
  40. 40.
    Hide M, Park HS, Igarashi A, Ye YM, Kim TB, Yagami A, et al. Efficacy and safety of omalizumab in Japanese and Korean patients with refractory chronic spontaneous urticaria. J Dermatol Sci. 2017;87(1):70–8.PubMedGoogle Scholar
  41. 41.
    Casale TB, Murphy TR, Holden M, Rajput Y, Yoo B, Bernstein JA. Impact of omalizumab on patient-reported outcomes in chronic idiopathic urticaria: results from a randomized study (XTEND-CIU). J Allergy Clin Immunol Pract. 2019.Google Scholar
  42. 42.
    Staubach P, Metz M, Chapman-Rothe N, Sieder C, Brautigam M, Canvin J, et al. Effect of omalizumab on angioedema in H1 -antihistamine-resistant chronic spontaneous urticaria patients: results from X-ACT, a randomized controlled trial. Allergy. 2016;71(8):1135–44.PubMedGoogle Scholar
  43. 43.
    • Metz M, Torene R, Kaiser S, Beste MT, Staubach P, Bauer A, et al. Omalizumab normalizes the gene expression signature of lesional skin in patients with chronic spontaneous urticaria: a randomized, double-blind, placebo-controlled study. Allergy. 2019;74(1):141–51 The first study to demonstrate changes in skin gene expression with omalizumab.PubMedGoogle Scholar
  44. 44.
    Maurer M, Fluhr JW, Khan DA. How to approach chronic inducible Urticaria. J Allergy Clin Immunol Pract. 2018;6(4):1119–30.PubMedGoogle Scholar
  45. 45.
    Vietri J, Turner SJ, Tian H, Isherwood G, Balp MM, Gabriel S. Effect of chronic urticaria on US patients: analysis of the National Health and ellness survey. Ann Allergy Asthma Immunol. 2015;115(4):306–11.PubMedGoogle Scholar
  46. 46.
    Weldon D. Quality of life in patients with urticaria and angioedema: assessing burden of disease. Allergy Asthma Proc. 2014;35(1):4–9.PubMedGoogle Scholar
  47. 47.
    Maurer M, Metz M, Brehler R, Hillen U, Jakob T, Mahler V, et al. Omalizumab treatment in patients with chronic inducible urticaria: a systematic review of published evidence. J Allergy Clin Immunol. 2018;141(2):638–49.PubMedGoogle Scholar
  48. 48.
    Ghazanfar MN, Sand C, Thomsen SF. Effectiveness and safety of omalizumab in chronic spontaneous or inducible urticaria: evaluation of 154 patients. Br J Dermatol. 2016;175(2):404–6.PubMedGoogle Scholar
  49. 49.
    Nettis E, Cegolon L, Di Leo E, Lodi Rizzini F, Detoraki A, Canonica GW, et al. Omalizumab chronic spontaneous urticaria: Efficacy, safety, predictors of treatment outcome, and time to response. Ann Allergy Asthma Immunol. 2018;121(4):474–8.PubMedGoogle Scholar
  50. 50.
    Weller K, Ohanyan T, Hawro T, Ellrich A, Sussman G, Koplowitz J, et al. Total IgE levels are linked to the response of chronic spontaneous urticaria patients to omalizumab. Allergy. 2018;73(12):2406–8.PubMedGoogle Scholar
  51. 51.
    Jorg L, Pecaric-Petkovic T, Reichenbach S, Coslovsky M, Stalder O, Pichler W, et al. Double-blind placebo-controlled trial of the effect of omalizumab on basophils in chronic urticaria patients. Clin Exp Allergy. 2018;48(2):196–204.PubMedGoogle Scholar
  52. 52.
    Ertas R, Ozyurt K, Atasoy M, Hawro T, Maurer M. The clinical response to omalizumab in chronic spontaneous urticaria patients is linked to and predicted by IgE levels and their change. Allergy. 2018;73(3):705–12.PubMedGoogle Scholar
  53. 53.
    Curto-Barredo L, Spertino J, Figueras-Nart I, Exposito-Serrano V, Guilabert A, Mele-Ninot G, et al. Omalizumab updosing allows disease activity control in patients with refractory chronic spontaneous urticaria. Br J Dermatol. 2018;179(1):210–2.PubMedGoogle Scholar
  54. 54.
    Niemeyer-van der Kolk T, van Maaren MS, van Doorn MB. Personalized omalizumab treatment improves clinical benefit in patients with chronic spontaneous urticaria. J Allergy Clin Immunol. 2018;142(6):1992–4.PubMedGoogle Scholar
  55. 55.
    Vadasz Z, Tal Y, Rotem M, Shichter-Confino V, Mahlab-Guri K, Graif Y, et al. Omalizumab for severe chronic spontaneous urticaria: real-life experiences of 280 patients. J Allergy Clin Immunol Pract. 2017;5(6):1743–5.PubMedGoogle Scholar
  56. 56.
    Tonacci A, Billeci L, Pioggia G, Navarra M, Gangemi S. Omalizumab for the treatment of chronic idiopathic urticaria: systematic review of the literature. Pharmacotherapy. 2017;37(4):464–80.PubMedGoogle Scholar
  57. 57.
    Turk M, Kocaturk E, Cure K, Yilmaz I. Two-week intervals during omalizumab treatment may provide better symptom control in selected patients with chronic urticaria. J Allergy Clin Immunol Pract. 2018;6(4):1389–90.PubMedGoogle Scholar
  58. 58.
    Ferrer M, Boccon-Gibod I, Goncalo M, Inaloz HS, Knulst A, Lapeere H, et al. Expert opinion: defining response to omalizumab in patients with chronic spontaneous urticaria. Eur J Dermatol. 2017;27(5):455–63.PubMedGoogle Scholar
  59. 59.
    Turk M, Maurer M, Yilmaz I. How to discontinue omalizumab in chronic spontaneous urticaria? Allergy. 2019;74(4):821–4.PubMedGoogle Scholar
  60. 60.
    Yang C, Cho Y, Chu C. Efficacy of omalizumab treatment for patients with chronic idiopathic urticaria (CIU)/chronic spontaneous urticaria (CSU) in Taiwan. Dermatol Sin. 2017;35:182–6.Google Scholar
  61. 61.
    Uysal P, Eller E, Mortz CG, Bindslev-Jensen C. An algorithm for treating chronic urticaria with omalizumab: dose interval should be individualized. J Allergy Clin Immunol. 2014;133(3):914–5 e2.PubMedGoogle Scholar
  62. 62.
    Ghazanfar MN, Thomsen S. Transient hair loss in patient with chronic spontaneous urticaria treated with omalizumab. Eur Ann Allergy Clin Immunol. 2017;49(6):284–5.Google Scholar
  63. 63.
    Konstantinou GN, Chioti AG, Daniilidis M. Self-reported hair loss in patients with chronic spontaneous urticaria treated with omalizumab: an under-reported, transient side effect? Eur Ann Allergy Clin Immunol. 2016;48(5):205–7.PubMedGoogle Scholar
  64. 64.
    Kronborg C, Pumar M, Gillman A. The first case of methemoglobinemia associated with omalizumab. J Allergy Clin Immunol Pract. 2018;6(4):1414–5.PubMedGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Department of Internal Medicine, Division of Allergy and ImmunologyUniversity of Texas Southwestern Medical CenterDallasUSA

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