Effectiveness and safety of Omalizumab in the treatment of chronic spontaneous urticaria: Systematic review and meta-analysis
Main Article Content
Keywords
Omalizumab, anti-IgE monoclonal antibody, anti-IgE, Chronic urticaria
Abstract
Introduction: Chronic spontaneous urticaria (CSU) affects approximately 1% of the population, affecting both children and adults. Omalizumab (Oma) is a therapeutic option for patients with refractory forms of CSU.
Objectives: To determine the effectiveness and safety of Oma in the treatment of CSU.
Methods: Systematic review (Cochrane Collaboration methodology) of randomized clinical trials comparing Oma to placebo in refractory CSU treatment. The search is based on MEDLINE; EMBASE, Central Cochrane Library, and LILACS. The outcomes evaluated were: control of the illness, adverse events, and quality of life.
Results: Of the 848 identified studies 13 were selected for further review and six were included in the meta-analysis. For all outcomes, high-quality evidence has confirmed that Oma is effective in the treatment of CSU. The dosage of 300 mg/month achieved better results; namely a significant reduction in pruritus, papules, and urticaria activity, as well as an increase in the number of patients with a controlled condition, improvement in the quality of life and no differences in adverse events compared to the placebo.
Conclusions: High-quality evidence demonstrates that Oma is effective and safe in the treatment of CSU refractory to therapy with H1 antihistamines.
References
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3. Balp MM, da Silva NL, Vietri J, Tian H, Ensina LF. The burden of chronic urticaria from Brazilian patients’ perspective. Dermatol Ther (Heidelb). 2017;69:1-11, http://dx.doi.org/10.1007/s13555-017-0191-4.
4. Dias GA, Pires GV, Valle SO, Dortas SD Jr, Levy S, Franc¸a AT, et al. Impact of chronic urticaria on the quality of life of patients followed up at a university hospital. An Bras Dermatol. 2016;91:754-9, http://dx.doi.org/10.1111/j.1398-9995.2011.02695.x.
5. Staevska M, Popov TA, Kralimarkova T, Lazarova C, Kraeva S, Popova D, et al. The effectiveness of levocetirizine and desloratadine in up to 4 times conventional doses in difficultto-treat urticaria. J Allergy Clin Immunol. 2010;125:676-82, http://dx.doi.org/10.1016/j.jaci.2009.11.047.
6. Higgins JPT, Green S, editors. Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. The Cochrane Collaboration; 2011. Available from www.cochrane-handbook.org. Accessed in April 2018.
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9. Lapi F, Cassano N, Pegoraro V, Cataldo N, Heiman F, Cricelli I, et al. Epidemiology of chronic urticaria: results from a Nationwide, population-based study in Italy. Br J Dermatol. 2016;174:996-1004, http://dx.doi.org/10.1111/bjd.14470.
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14. Maurer M, Altrichter S, Bieber T, Biedermann T, Bräutigam 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, http://dx.doi.org/10.1016/j.jaci.2011.04.038.
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19. Staubach P, Metz M, Chapman-Rothe N, Sieder C, Bräutigam 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, http://dx.doi.org/10.1111/all.12870.
20. Staubach P, Metz M, Chapman-Rothe N, Sieder C, Bräutigam M, Maurer M, et al. Omalizumab rapidly improves angioedema-related quality of life in adult patients with chronic spontaneous urticaria: X-ACT study data. Allergy. 2018;73(3):576-84, http://dx.doi.org/10.1111/all.13339.
21. Finlay AY, Kaplan AP, Beck LA, Antonova EN, Balp MM, Zazzali J, et al. Omalizumab substantially improves dermatology-related quality of life in patients with chronic spontaneous urticaria. J Eur Acad Dermatol Venereol. 2017;31(10):1715-21, http://dx.doi.org/10.1111/jdv.14384.
22. 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, http://dx.doi.org/10.1016/j.jdermsci.2017.03.009.
23. Maurer M, Rosen K, Hsieh HJ, Saini S, Grattan C, Gimenez-Arnau A, et al. Omalizumab for the treatment of chronic idiophatic or spontaneous urticaria. N Engl J Med. 2013;368:924-35, http://dx.doi.org/10.1056/NEJMoa1215372.
24. Metz M, Staubach P, Bauer A, Brehler R, Gericke J, AshtonChess J, et al. Omalizumab normalizes levels of high-affinity immunoglobulin E receptor-positive skin mast cells in patients with chronic spontaneous urticaria: a randomized, double-blind, placebo-controlled study. J Invest Dermatol. 2014;134:S30-8, http://dx.doi.org/10.7150/thno.18304.
25. Bernstein JA, Kavati A, Tharp MD, Ortiz B, MacDonald K, Denhaerynck K, et al. Effectiveness of omalizumab in adolescent and adult patients with chronic idiopathic/spontaneous urticaria: a systematic review of’ real world’ evidence. Expert Opin Biol Ther. 2018;18(4):425-48, http://dx.doi.org/10.1080/14712598.2018.1438406.
26. Salek MS, Jung S, Brincat-Ruffini LA, MacFarlane L, Lewis-Jones MS, Basra MK, et al. Clinical experience and psychometric properties of the Children’s Dermatology Life Quality Index (CDLQI), 1995-2012. Br J Dermatol. 2013;169(4):734-59, http://dx.doi.org/10.1111/bjd.12437.
27. Morgan M, McCreedy R, Simpson J, Hay RJ. Dermatology quality of life scales-a measure of the impact of skin diseases. Br J Dermatol. 1997;136(2):202-6.
28. Anderson RT, Rajagopalan R. Development and validation of a quality of life instrument for cutaneous diseases. J Am Acad Dermatol. 1997;37(1):41-50.
29. Chren MM, Lasek RJ, Flocke SA, Zyzanski SJ. Improved discriminative and evaluative capability of a refined version of Skindex, a quality-of-life instrument for patients with skin diseases. Arch Dermatol. 1997;133:1433-40.
30. Chren MM, Lasek RJ, Sahay AP, Sands LP. Measurement properties of Skindex-16: a brief quality-of-life measure for patients with skin diseases. J Cutan Med Surg. 2001;5(2):105-10, http://dx.doi.org/10.1177/120347540100500202.
31. 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-Q2oL). Allergy. 2005;60:1073-8, http://dx.doi.org/10.1111/j.1398-9995.2005.00833.x.
32. Jariwala SP, Moday H, de Asis L, Fodeman J, Hudes G, de Vos G, et al. The Urticaria Severity Score: a sensitive questionnaire/index for monitoring response to therapy in patients with chronic urticaria. Ann Allergy Asthma Immunol. 2009;102:475-82, http://dx.doi.org/10.1016/S1081-1206(10)60120-2.
33. 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(2):80-6.
34. Weller K, Groffik A, Magerl M, Tohme N, Martus P, Krause K, et al. Development and construct validation of the angioedema quality of life questionnaire. Allergy. 2012;67(10):1289-98, http://dx.doi.org/10.1111/all.12007.
35. Carrillo DC, Borges MS, García E, Egea E, Serrano CD. Omalizumab vs. placebo in the management of chronic idiopathic urticaria: a systematic review. World Allergy Organ J. 2014;7(1):72, http://dx.doi.org/10.1186/s40413-014-0050-z.
36. Urgert MC, van den Elzen MT, Knulst AC, Fedorowicz Z, van Zuuren EJ. Omalizumab in patients with chronic spontaneous urticaria: a systematic review and GRADE assessment. Br J Dermatol. 2015;173(2):404-15, http://dx.doi.org/10.1111/bjd.13845.
37. Zhao ZT, Ji CM, Yu WJ, Meng L, Hawro T, Wei JF, et al. Omalizumab for the treatment of chronic spontaneous urticaria: a meta analysis of randomized clinical trials. J Allergy Clin Immunol. 2016;137(6):1742-50, http://dx.doi.org/10.1016/j.jaci.2015.12.1342.
38. van der Valk P, Moret G, Kiemeney L. The natural history of chronic urticaria and angioedema in patients visiting a tertiary referral centre. Br J Dermatol. 2002;146:110-3.
39. Sanchez-Borges M, Caballero-Fonseca F, Capriles-Hulett A, González-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;31:964-71, http://dx.doi.org/10.1111/jdv.14221.
40. Kulthanan K, Jiamton S, Thumpimukvatana N, Pinkaew S. Chronic idiopathic urticaria: prevalence and clinical course. J Dermatol. 2007;34:294-301, http://dx.doi.org/10.1111/j.1346-8138.2007.00276.x.
2. Zuberbier T, Aberer W, Asero R, Abdul Latiff AH, Baker D, Ballmer-Weber B, et al. The EAACI/GA2LEN/EDF/WAO guideline for the definition, classification, diagnosis and management of urticaria. Allergy. 2018;73:1393---414, http://dx.doi.org/10.1111/all.13397.
3. Balp MM, da Silva NL, Vietri J, Tian H, Ensina LF. The burden of chronic urticaria from Brazilian patients’ perspective. Dermatol Ther (Heidelb). 2017;69:1-11, http://dx.doi.org/10.1007/s13555-017-0191-4.
4. Dias GA, Pires GV, Valle SO, Dortas SD Jr, Levy S, Franc¸a AT, et al. Impact of chronic urticaria on the quality of life of patients followed up at a university hospital. An Bras Dermatol. 2016;91:754-9, http://dx.doi.org/10.1111/j.1398-9995.2011.02695.x.
5. Staevska M, Popov TA, Kralimarkova T, Lazarova C, Kraeva S, Popova D, et al. The effectiveness of levocetirizine and desloratadine in up to 4 times conventional doses in difficultto-treat urticaria. J Allergy Clin Immunol. 2010;125:676-82, http://dx.doi.org/10.1016/j.jaci.2009.11.047.
6. Higgins JPT, Green S, editors. Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. The Cochrane Collaboration; 2011. Available from www.cochrane-handbook.org. Accessed in April 2018.
7. Mathias SD, Crosby RD, Zazzali JL, Maurer M, Saini SS. Evaluating the minimally important difference of the urticaria activity score and other measures of disease activity in patients with chronic idiopathic urticaria. Ann Allergy Asthma Immunol. 2012;108:20-4, http://dx.doi.org/10.1016/j.anai.2011.09.008.
8. 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;132:101-9, http://dx.doi.org/10.1016/j.jaci.2013.05.013.
9. Lapi F, Cassano N, Pegoraro V, Cataldo N, Heiman F, Cricelli I, et al. Epidemiology of chronic urticaria: results from a Nationwide, population-based study in Italy. Br J Dermatol. 2016;174:996-1004, http://dx.doi.org/10.1111/bjd.14470.
10. Finlay AY, Khan GK. Dermatology Life Quality Index (DLQI)-a simple practical measure for routine clinical use. Clin Exp Dermatol. 1994;19:210-6.
11. Shikiar R, Harding G, Leahy M, Lennox RD. Minimal important difference (MID) of the Dermatology Life Quality Index (DLQI): results from patients with chronic idiopathic urticaria. Health Qual Life Outcomes. 2005;3:36, http://dx.doi.org/10.1186/1477-7525-3-36.
12. Review Manager (RevMan) [Computer program]. Version 5.2. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration; 2014.
13. Gober LM, Sterba PM, Eckman JA, Saini SS. Effect of anti-IgE (omalizumab) in chronic idiopathic urticaria (CIU) patients. J Allergy Clin Immunol. 2008;121(2): S147.
14. Maurer M, Altrichter S, Bieber T, Biedermann T, Bräutigam 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, http://dx.doi.org/10.1016/j.jaci.2011.04.038.
15. Hide M, Igarashi A, Yagami A, Chinuki Y, Inomata N, Fukunaga A, et al. Efficacy and safety of omalizumab for the treatment of refractory chronic spontaneous urticaria in Japanese patients: subgroup analysis of the phase 3 POLARIS study. Allergol Int. 2018;67(2):243-52, http://dx.doi.org/10.1016/j.alit.2017.10.001.
16. Jörg 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, http://dx.doi.org/10.1111/cea.13066.
17. 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, http://dx.doi.org/10.1016/j.jaci.2011.06.010.
18. 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;135:925, http://dx.doi.org/10.1038/jid.2014.512.
19. Staubach P, Metz M, Chapman-Rothe N, Sieder C, Bräutigam 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, http://dx.doi.org/10.1111/all.12870.
20. Staubach P, Metz M, Chapman-Rothe N, Sieder C, Bräutigam M, Maurer M, et al. Omalizumab rapidly improves angioedema-related quality of life in adult patients with chronic spontaneous urticaria: X-ACT study data. Allergy. 2018;73(3):576-84, http://dx.doi.org/10.1111/all.13339.
21. Finlay AY, Kaplan AP, Beck LA, Antonova EN, Balp MM, Zazzali J, et al. Omalizumab substantially improves dermatology-related quality of life in patients with chronic spontaneous urticaria. J Eur Acad Dermatol Venereol. 2017;31(10):1715-21, http://dx.doi.org/10.1111/jdv.14384.
22. 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, http://dx.doi.org/10.1016/j.jdermsci.2017.03.009.
23. Maurer M, Rosen K, Hsieh HJ, Saini S, Grattan C, Gimenez-Arnau A, et al. Omalizumab for the treatment of chronic idiophatic or spontaneous urticaria. N Engl J Med. 2013;368:924-35, http://dx.doi.org/10.1056/NEJMoa1215372.
24. Metz M, Staubach P, Bauer A, Brehler R, Gericke J, AshtonChess J, et al. Omalizumab normalizes levels of high-affinity immunoglobulin E receptor-positive skin mast cells in patients with chronic spontaneous urticaria: a randomized, double-blind, placebo-controlled study. J Invest Dermatol. 2014;134:S30-8, http://dx.doi.org/10.7150/thno.18304.
25. Bernstein JA, Kavati A, Tharp MD, Ortiz B, MacDonald K, Denhaerynck K, et al. Effectiveness of omalizumab in adolescent and adult patients with chronic idiopathic/spontaneous urticaria: a systematic review of’ real world’ evidence. Expert Opin Biol Ther. 2018;18(4):425-48, http://dx.doi.org/10.1080/14712598.2018.1438406.
26. Salek MS, Jung S, Brincat-Ruffini LA, MacFarlane L, Lewis-Jones MS, Basra MK, et al. Clinical experience and psychometric properties of the Children’s Dermatology Life Quality Index (CDLQI), 1995-2012. Br J Dermatol. 2013;169(4):734-59, http://dx.doi.org/10.1111/bjd.12437.
27. Morgan M, McCreedy R, Simpson J, Hay RJ. Dermatology quality of life scales-a measure of the impact of skin diseases. Br J Dermatol. 1997;136(2):202-6.
28. Anderson RT, Rajagopalan R. Development and validation of a quality of life instrument for cutaneous diseases. J Am Acad Dermatol. 1997;37(1):41-50.
29. Chren MM, Lasek RJ, Flocke SA, Zyzanski SJ. Improved discriminative and evaluative capability of a refined version of Skindex, a quality-of-life instrument for patients with skin diseases. Arch Dermatol. 1997;133:1433-40.
30. Chren MM, Lasek RJ, Sahay AP, Sands LP. Measurement properties of Skindex-16: a brief quality-of-life measure for patients with skin diseases. J Cutan Med Surg. 2001;5(2):105-10, http://dx.doi.org/10.1177/120347540100500202.
31. 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-Q2oL). Allergy. 2005;60:1073-8, http://dx.doi.org/10.1111/j.1398-9995.2005.00833.x.
32. Jariwala SP, Moday H, de Asis L, Fodeman J, Hudes G, de Vos G, et al. The Urticaria Severity Score: a sensitive questionnaire/index for monitoring response to therapy in patients with chronic urticaria. Ann Allergy Asthma Immunol. 2009;102:475-82, http://dx.doi.org/10.1016/S1081-1206(10)60120-2.
33. 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(2):80-6.
34. Weller K, Groffik A, Magerl M, Tohme N, Martus P, Krause K, et al. Development and construct validation of the angioedema quality of life questionnaire. Allergy. 2012;67(10):1289-98, http://dx.doi.org/10.1111/all.12007.
35. Carrillo DC, Borges MS, García E, Egea E, Serrano CD. Omalizumab vs. placebo in the management of chronic idiopathic urticaria: a systematic review. World Allergy Organ J. 2014;7(1):72, http://dx.doi.org/10.1186/s40413-014-0050-z.
36. Urgert MC, van den Elzen MT, Knulst AC, Fedorowicz Z, van Zuuren EJ. Omalizumab in patients with chronic spontaneous urticaria: a systematic review and GRADE assessment. Br J Dermatol. 2015;173(2):404-15, http://dx.doi.org/10.1111/bjd.13845.
37. Zhao ZT, Ji CM, Yu WJ, Meng L, Hawro T, Wei JF, et al. Omalizumab for the treatment of chronic spontaneous urticaria: a meta analysis of randomized clinical trials. J Allergy Clin Immunol. 2016;137(6):1742-50, http://dx.doi.org/10.1016/j.jaci.2015.12.1342.
38. van der Valk P, Moret G, Kiemeney L. The natural history of chronic urticaria and angioedema in patients visiting a tertiary referral centre. Br J Dermatol. 2002;146:110-3.
39. Sanchez-Borges M, Caballero-Fonseca F, Capriles-Hulett A, González-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;31:964-71, http://dx.doi.org/10.1111/jdv.14221.
40. Kulthanan K, Jiamton S, Thumpimukvatana N, Pinkaew S. Chronic idiopathic urticaria: prevalence and clinical course. J Dermatol. 2007;34:294-301, http://dx.doi.org/10.1111/j.1346-8138.2007.00276.x.
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Rubini, N., Ensina, L., Silva, E., Sano, F., & Solé, D. (2019). Effectiveness and safety of Omalizumab in the treatment of chronic spontaneous urticaria: Systematic review and meta-analysis. Allergologia Et Immunopathologia, 47(6), 515-522. https://all-imm.com/index.php/aei/article/view/264
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Rubini, N., Ensina, L., Silva, E., Sano, F., & Solé, D. (2019). Effectiveness and safety of Omalizumab in the treatment of chronic spontaneous urticaria: Systematic review and meta-analysis. Allergologia Et Immunopathologia, 47(6), 515-522. https://all-imm.com/index.php/aei/article/view/264