Biomarkers of response to omalizumab in patients with chronic spontaneous urticaria
Main Article Content
Keywords
chronic spontaneous urticaria, immunoglobulin E, omalizumab, urticaria activity score
Abstract
Background and Objectives: Managing chronic spontaneous urticaria (CSU) resistant to anti-histamines remains challenging, and predictors of omalizumab efficacy are not fully understood. This study evaluated omalizumab’s effectiveness, response patterns, and predictors in CSU patients.
Materials and Methods: A retrospective analysis was conducted on 72 patients receiving omalizumab for at least six months. Factors influencing response to anti-IgE therapy were examined.
Results: Among the 72 patients with chronic spontaneous urticaria (CSU), 86.1% responded to omalizumab: 58.3% had a good response (UAS-7 <6), 27.8% showed a partial response, and 13.9% were non-responders. Baseline total IgE levels were significantly higher in responders compared to non-responders (good: 291.4 kUA/L vs. 60.2 kUA/L, p = 0.003; partial: 148 kUA/L vs. 60.2 kUA/L, p = 0.049). ROC analysis identified a total IgE cut-off of 64 kUA/L for predicting omalizumab response (AUC: 0.67, p = 0.019; sensitivity: 82%, specificity: 48%). Non-responders had significantly higher erythrocyte sedimentation rates (20.0 mm/h vs. 8.25 mm/h, p = 0.018). Patients with recurrence post-treatment had elevated thyroid-stimulating hormone (TSH) and C-reactive protein (CRP) levels (p = 0.006, p = 0.007). Among responders, 29% had an early response and 71% a late response. Early responders had significantly lower anti-thyroglobulin (anti-TG) and antinuclear antibody (ANA) positivity (p = 0.036, p = 0.035). Systemic inflammatory indices (SII, SIRI) did not predict response.
Conclusions: Baseline total IgE may predict omalizumab response, while ANA and anti-TG positivity correlate with delayed response. Elevated TSH and CRP levels may indicate a higher recurrence risk after treatment discontinuation.
References
1 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(7):1393–414. 10.1111/all.13397
2 Fricke J, Ávila G, Keller T, Weller K, Lau S, Maurer M, et al. Prevalence of chronic urticaria in children and adults across the globe: Systematic review with meta-analysis. Allergy. 2020;75(2):423–32. 10.1111/all.14037
3 Ferrer M, Kinét JP, Kaplan AP. Comparative studies of functional and binding assays for IgG anti-Fc(epsilon)RIalpha (alpha-subunit) in chronic urticaria. J Allergy Clin Immunol. 1998;101(5):672–6. 10.1016/s0091-6749(98)70176-9
4 Hide M, Francis DM, Grattan CE, Hakimi J, Kochan JP, Greaves MW. Autoantibodies against the high-affinity IgE receptor as a cause of histamine release in chronic urticaria. N Engl J Med. 1993;328(22):1599–604. 10.1056/NEJM199306033282204
5 Asero R, Tedeschi A, Riboldi P, Griffini S, Bonanni E, Cugno M. Severe chronic urticaria is associated with elevated plasma levels of D-dimer. Allergy. 2008;63(2):176–80. 10.1111/j.1398-9995.2007.01514.x
6 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. 10.1016/j.jaci.2011.06.010
7 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.e4. 10.1016/j.jaci.2015.12.1342
8 Kaplan AP, Giménez-Arnau AM, Saini SS. Mechanisms of action that contribute to efficacy of omalizumab in chronic spontaneous urticaria. Allergy. 2017;72(4):519–33. 10.1111/all.13083
9 Zuberbier T, Abdul Latiff AH, Abuzakouk M, Aquilina S, Asero R, Baker D, et al. The international EAACI/GA2LEN/EuroGuiDerm/APAAACI guideline for the definition, classification, diagnosis, and management of urticaria. Allergy. 2022;77(3):734–66. 10.1111/all.15090
10 Marzano AV, Genovese G, Casazza G, Fierro MT, Dapavo P, Crimi N, et al. Predictors of response to omalizumab and relapse in chronic spontaneous urticaria: a study of 470 patients. J Eur Acad Dermatol Venereol. 2019;33(5):918–24. 10.1111/jdv.15350
11 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. 10.1111/all.13345
12 Kaplan A, Ferrer M, Bernstein JA, Antonova E, Trzaskoma B, Raimundo K, et al. Timing and duration of omalizumab response in patients with chronic idiopathic/spontaneous urticaria. J Allergy Clin Immunol. 2016;137(2):474–81. 10.1016/j.jaci.2015.08.023
13 Chen J, Ou S, Wu W, Zou H, Li H, Zhu H. Omalizumab in Chronic Spontaneous Urticaria: A Real-World Study on Effectiveness, Safety and Predictors of Treatment Outcome. Clin Cosmet Investig Dermatol. 2024;17:1799–808. 10.2147/CCID.S470160
14 Ertas R, Ozyurt K, Ozlu E, Ulas Y, Avci A, Atasoy M, et al. Increased IgE levels are linked to faster relapse in patients with omalizumab-discontinued chronic spontaneous urticaria. J Allergy Clin Immunol. 2017;140(6):1749–51. 10.1016/j.jaci.2017.08.007
15 Chuang K-W, Hsu C-Y, Huang S-W, Chang H-C. Association Between Serum Total IgE Levels and Clinical Response to Omalizumab for Chronic Spontaneous Urticaria: A Systematic Review and Meta-Analysis. J Allergy Clin Immunol Pract. 2023;11(8):2382–9.e3. 10.1016/j.jaip.2023.05.033
16 Lee HY, Jeon HS, Jang JH, Lee Y, Shin YS, Nahm DH, et al. Predicting responses to omalizumab in antihistamine-refractory chronic urticaria: A real-world longitudinal study. J Allergy Clin Immunol Glob. 2024;3(2):100245. 10.1016/j.jacig.2024.100245
17 Du Z, Zhi Y. Predictors of response to omalizumab in chronic spontaneous urticaria. J Allergy Clin Immunol. 2023;151(2):AB208.
18 Lee H-Y, Jeon H-S, Jang J-H, Lee Y, Shin YS, Nahm D-H, et al. Predicting responses to omalizumab in antihistamine-refractory chronic urticaria: A real-world longitudinal study. J Allergy Clin Immunol Glob. 2024;3(2):100245. 10.1016/j.jacig.2024.100245
19 Fok JS, Kolkhir P, Church MK, Maurer M. Predictors of treatment response in chronic spontaneous urticaria. Allergy. 2021;76(10):2965–81. 10.1111/all.14757
20 Asero R, Marzano AV, Ferrucci S, Cugno M. D-Dimer Plasma Levels Parallel the Clinical Response to Omalizumab in Patients with Severe Chronic Spontaneous Urticaria. Int Arch Allergy Immunol. 2017;172(1):40–4. 10.1159/000453453
21 Diluvio L, Piccolo A, Marasco F, Vollono L, Lanna C, Chiaramonte B, et al. Improving of psychological status and inflammatory biomarkers during omalizumab for chronic spontaneous urticaria. Future Sci OA. 2020;6(9):Fso618. 10.2144/fsoa-2020-0087
22 Yu R, Qian W, Zheng Q, Xiong J, Chen S, Chen A, et al. Analysis of the Efficacy and Recurrence of Omalizumab Use in the Treatment of Chronic Spontaneous Urticaria and Chronic Inducible Urticaria. Int Arch Allergy Immunol. 2023;184(7):643–55. 10.1159/000529250
23 Ferrer M, Giménez-Arnau A, Saldana D, Janssens N, Balp MM, Khalil S, et al. Predicting Chronic Spontaneous Urticaria Symptom Return After Omalizumab Treatment Discontinuation: Exploratory Analysis. J Allergy Clin Immunol Pract. 2018;6(4):1191–7.e5. 10.1016/j.jaip.2018.04.003
24 Oztop N, Demir S, Unal D, Beyaz S, Terzioglu K, Olgac M, et al. Predictive factors of recurrence after omalizumab cessation in the elderly with urticaria: A real-life study. Allergy Asthma Proc. 2022;43(6):519–28. 10.2500/aap.2022.43.220068
25 Meertens MAJ, Luijf T, van Lindonk EAM, Soegiharto R, Assil S, Alizadeh Aghdam M, et al. Age and fast initial response predict omalizumab retreatment in chronic urticaria. J Allergy Clini Immunol Pract. 2023;11(11):3556–8.e1. 10.1016/j.jaip.2023.07.030
26 Grieco T, Dies L, Sernicola A, Chello C, Gagliostro N, Carnicelli G, et al. Potential clinical and serological predictors of chronic spontaneous urticaria relapse in patients under omalizumab treatment. Immunotherapy. 2020;12(16):1173–81. 10.2217/imt-2020-0088
27 Kasperska-Zajac A. Acute-phase response in chronic urticaria. J Eur Acad Dermatol Venereol. 2012;26(6):665–72. 10.1111/j.1468-3083.2011.04366.x
28 Kasperska-Zajac A, Sztylc J, Machura E, Jop G. Plasma IL-6 concentration correlates with clinical disease activity and serum C-reactive protein concentration in chronic urticaria patients. Clin Exp Allergy. 2011;41(10):1386–91. 10.1111/j.1365-2222.2011.03789.x
29 Kolkhir P, Altrichter S, Hawro T, Maurer M. C-reactive protein is linked to disease activity, impact, and response to treatment in patients with chronic spontaneous urticaria. Allergy. 2018;73(4):940–8. 10.1111/all.13352
30 de Montjoye L, Darrigade AS, Giménez-Arnau A, Herman A, Dumoutier L, Baeck M. Correlations between disease activity, autoimmunity and biological parameters in patients with chronic spontaneous urticaria. Eur Ann Allergy Clin Immunol. 2021;53(2):55–66. 10.23822/EurAnnACI.1764-1489.132
31 Kolkhir P, Altrichter S, Asero R, Daschner A, Ferrer M, Giménez-Arnau A, et al. Autoimmune Diseases Are Linked to Type IIb Autoimmune Chronic Spontaneous Urticaria. Allergy Asthma Immunol Res. 2021;13(4):545–59. 10.4168/aair.2021.13.4.545
32 Zubiaga-Fernandez L, Testera-Montes A, Rondon C, Perez-Sanchez N, Gomez-Perez F, Vega-Chicote JM, et al. Biomarkers predicting the controller dose of omalizumab in patients with chronic spontaneous urticaria. Clin Exp Allergy. 2024;54(6):402–11. 10.1111/cea.14462
33 Kolkhir P, Borzova E, Grattan C, Asero R, Pogorelov D, Maurer M. Autoimmune comorbidity in chronic spontaneous urticaria: A systematic review. Autoimmun Rev. 2017;16(12):1196–208. 10.1016/j.autrev.2017.10.003
34 Brás R, Esteves Caldeira L, Bernardino A, Costa C. Anti-TPO IgG/Total IgE Ratio: Biomarker for Omalizumab Response Prediction in Chronic Spontaneous Urticaria. Int Arch Allergy Immunol. 2023;184(9):866–9. 10.1159/000532021
35 Casale TB, Win PH, Bernstein JA, Rosén K, Holden M, Iqbal A, et al. Omalizumab response in patients with chronic idiopathic urticaria: Insights from the XTEND-CIU study. J Am Acad Dermatol. 2018;78(4):793–5. 10.1016/j.jaad.2017.10.010
36 Gericke J, Metz M, Ohanyan T, Weller K, Altrichter S, Skov PS, et al. Serum autoreactivity predicts time to response to omalizumab therapy in chronic spontaneous urticaria. J Allergy Clin Immunol. 2017;139(3):1059–61.e1. 10.1016/j.jaci.2016.07.047
2 Fricke J, Ávila G, Keller T, Weller K, Lau S, Maurer M, et al. Prevalence of chronic urticaria in children and adults across the globe: Systematic review with meta-analysis. Allergy. 2020;75(2):423–32. 10.1111/all.14037
3 Ferrer M, Kinét JP, Kaplan AP. Comparative studies of functional and binding assays for IgG anti-Fc(epsilon)RIalpha (alpha-subunit) in chronic urticaria. J Allergy Clin Immunol. 1998;101(5):672–6. 10.1016/s0091-6749(98)70176-9
4 Hide M, Francis DM, Grattan CE, Hakimi J, Kochan JP, Greaves MW. Autoantibodies against the high-affinity IgE receptor as a cause of histamine release in chronic urticaria. N Engl J Med. 1993;328(22):1599–604. 10.1056/NEJM199306033282204
5 Asero R, Tedeschi A, Riboldi P, Griffini S, Bonanni E, Cugno M. Severe chronic urticaria is associated with elevated plasma levels of D-dimer. Allergy. 2008;63(2):176–80. 10.1111/j.1398-9995.2007.01514.x
6 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. 10.1016/j.jaci.2011.06.010
7 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.e4. 10.1016/j.jaci.2015.12.1342
8 Kaplan AP, Giménez-Arnau AM, Saini SS. Mechanisms of action that contribute to efficacy of omalizumab in chronic spontaneous urticaria. Allergy. 2017;72(4):519–33. 10.1111/all.13083
9 Zuberbier T, Abdul Latiff AH, Abuzakouk M, Aquilina S, Asero R, Baker D, et al. The international EAACI/GA2LEN/EuroGuiDerm/APAAACI guideline for the definition, classification, diagnosis, and management of urticaria. Allergy. 2022;77(3):734–66. 10.1111/all.15090
10 Marzano AV, Genovese G, Casazza G, Fierro MT, Dapavo P, Crimi N, et al. Predictors of response to omalizumab and relapse in chronic spontaneous urticaria: a study of 470 patients. J Eur Acad Dermatol Venereol. 2019;33(5):918–24. 10.1111/jdv.15350
11 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. 10.1111/all.13345
12 Kaplan A, Ferrer M, Bernstein JA, Antonova E, Trzaskoma B, Raimundo K, et al. Timing and duration of omalizumab response in patients with chronic idiopathic/spontaneous urticaria. J Allergy Clin Immunol. 2016;137(2):474–81. 10.1016/j.jaci.2015.08.023
13 Chen J, Ou S, Wu W, Zou H, Li H, Zhu H. Omalizumab in Chronic Spontaneous Urticaria: A Real-World Study on Effectiveness, Safety and Predictors of Treatment Outcome. Clin Cosmet Investig Dermatol. 2024;17:1799–808. 10.2147/CCID.S470160
14 Ertas R, Ozyurt K, Ozlu E, Ulas Y, Avci A, Atasoy M, et al. Increased IgE levels are linked to faster relapse in patients with omalizumab-discontinued chronic spontaneous urticaria. J Allergy Clin Immunol. 2017;140(6):1749–51. 10.1016/j.jaci.2017.08.007
15 Chuang K-W, Hsu C-Y, Huang S-W, Chang H-C. Association Between Serum Total IgE Levels and Clinical Response to Omalizumab for Chronic Spontaneous Urticaria: A Systematic Review and Meta-Analysis. J Allergy Clin Immunol Pract. 2023;11(8):2382–9.e3. 10.1016/j.jaip.2023.05.033
16 Lee HY, Jeon HS, Jang JH, Lee Y, Shin YS, Nahm DH, et al. Predicting responses to omalizumab in antihistamine-refractory chronic urticaria: A real-world longitudinal study. J Allergy Clin Immunol Glob. 2024;3(2):100245. 10.1016/j.jacig.2024.100245
17 Du Z, Zhi Y. Predictors of response to omalizumab in chronic spontaneous urticaria. J Allergy Clin Immunol. 2023;151(2):AB208.
18 Lee H-Y, Jeon H-S, Jang J-H, Lee Y, Shin YS, Nahm D-H, et al. Predicting responses to omalizumab in antihistamine-refractory chronic urticaria: A real-world longitudinal study. J Allergy Clin Immunol Glob. 2024;3(2):100245. 10.1016/j.jacig.2024.100245
19 Fok JS, Kolkhir P, Church MK, Maurer M. Predictors of treatment response in chronic spontaneous urticaria. Allergy. 2021;76(10):2965–81. 10.1111/all.14757
20 Asero R, Marzano AV, Ferrucci S, Cugno M. D-Dimer Plasma Levels Parallel the Clinical Response to Omalizumab in Patients with Severe Chronic Spontaneous Urticaria. Int Arch Allergy Immunol. 2017;172(1):40–4. 10.1159/000453453
21 Diluvio L, Piccolo A, Marasco F, Vollono L, Lanna C, Chiaramonte B, et al. Improving of psychological status and inflammatory biomarkers during omalizumab for chronic spontaneous urticaria. Future Sci OA. 2020;6(9):Fso618. 10.2144/fsoa-2020-0087
22 Yu R, Qian W, Zheng Q, Xiong J, Chen S, Chen A, et al. Analysis of the Efficacy and Recurrence of Omalizumab Use in the Treatment of Chronic Spontaneous Urticaria and Chronic Inducible Urticaria. Int Arch Allergy Immunol. 2023;184(7):643–55. 10.1159/000529250
23 Ferrer M, Giménez-Arnau A, Saldana D, Janssens N, Balp MM, Khalil S, et al. Predicting Chronic Spontaneous Urticaria Symptom Return After Omalizumab Treatment Discontinuation: Exploratory Analysis. J Allergy Clin Immunol Pract. 2018;6(4):1191–7.e5. 10.1016/j.jaip.2018.04.003
24 Oztop N, Demir S, Unal D, Beyaz S, Terzioglu K, Olgac M, et al. Predictive factors of recurrence after omalizumab cessation in the elderly with urticaria: A real-life study. Allergy Asthma Proc. 2022;43(6):519–28. 10.2500/aap.2022.43.220068
25 Meertens MAJ, Luijf T, van Lindonk EAM, Soegiharto R, Assil S, Alizadeh Aghdam M, et al. Age and fast initial response predict omalizumab retreatment in chronic urticaria. J Allergy Clini Immunol Pract. 2023;11(11):3556–8.e1. 10.1016/j.jaip.2023.07.030
26 Grieco T, Dies L, Sernicola A, Chello C, Gagliostro N, Carnicelli G, et al. Potential clinical and serological predictors of chronic spontaneous urticaria relapse in patients under omalizumab treatment. Immunotherapy. 2020;12(16):1173–81. 10.2217/imt-2020-0088
27 Kasperska-Zajac A. Acute-phase response in chronic urticaria. J Eur Acad Dermatol Venereol. 2012;26(6):665–72. 10.1111/j.1468-3083.2011.04366.x
28 Kasperska-Zajac A, Sztylc J, Machura E, Jop G. Plasma IL-6 concentration correlates with clinical disease activity and serum C-reactive protein concentration in chronic urticaria patients. Clin Exp Allergy. 2011;41(10):1386–91. 10.1111/j.1365-2222.2011.03789.x
29 Kolkhir P, Altrichter S, Hawro T, Maurer M. C-reactive protein is linked to disease activity, impact, and response to treatment in patients with chronic spontaneous urticaria. Allergy. 2018;73(4):940–8. 10.1111/all.13352
30 de Montjoye L, Darrigade AS, Giménez-Arnau A, Herman A, Dumoutier L, Baeck M. Correlations between disease activity, autoimmunity and biological parameters in patients with chronic spontaneous urticaria. Eur Ann Allergy Clin Immunol. 2021;53(2):55–66. 10.23822/EurAnnACI.1764-1489.132
31 Kolkhir P, Altrichter S, Asero R, Daschner A, Ferrer M, Giménez-Arnau A, et al. Autoimmune Diseases Are Linked to Type IIb Autoimmune Chronic Spontaneous Urticaria. Allergy Asthma Immunol Res. 2021;13(4):545–59. 10.4168/aair.2021.13.4.545
32 Zubiaga-Fernandez L, Testera-Montes A, Rondon C, Perez-Sanchez N, Gomez-Perez F, Vega-Chicote JM, et al. Biomarkers predicting the controller dose of omalizumab in patients with chronic spontaneous urticaria. Clin Exp Allergy. 2024;54(6):402–11. 10.1111/cea.14462
33 Kolkhir P, Borzova E, Grattan C, Asero R, Pogorelov D, Maurer M. Autoimmune comorbidity in chronic spontaneous urticaria: A systematic review. Autoimmun Rev. 2017;16(12):1196–208. 10.1016/j.autrev.2017.10.003
34 Brás R, Esteves Caldeira L, Bernardino A, Costa C. Anti-TPO IgG/Total IgE Ratio: Biomarker for Omalizumab Response Prediction in Chronic Spontaneous Urticaria. Int Arch Allergy Immunol. 2023;184(9):866–9. 10.1159/000532021
35 Casale TB, Win PH, Bernstein JA, Rosén K, Holden M, Iqbal A, et al. Omalizumab response in patients with chronic idiopathic urticaria: Insights from the XTEND-CIU study. J Am Acad Dermatol. 2018;78(4):793–5. 10.1016/j.jaad.2017.10.010
36 Gericke J, Metz M, Ohanyan T, Weller K, Altrichter S, Skov PS, et al. Serum autoreactivity predicts time to response to omalizumab therapy in chronic spontaneous urticaria. J Allergy Clin Immunol. 2017;139(3):1059–61.e1. 10.1016/j.jaci.2016.07.047
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Jul 1, 2025
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Öztürk Aktaş Özge, Öksüzer Çimşir D., Bülbül E. N., Şerbetçi, N., Fendoğlu, T. Z., İnan, E., Görgülü Akın B., Beyaz Şengül, Çelebi Sözener, Z., & Soyyiğit, Şadan. (2025). Biomarkers of response to omalizumab in patients with chronic spontaneous urticaria. Allergologia Et Immunopathologia, 53(4), 7–13. https://doi.org/10.15586/aei.v53i4.1443
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Öztürk Aktaş Özge, Öksüzer Çimşir D., Bülbül E. N., Şerbetçi, N., Fendoğlu, T. Z., İnan, E., Görgülü Akın B., Beyaz Şengül, Çelebi Sözener, Z., & Soyyiğit, Şadan. (2025). Biomarkers of response to omalizumab in patients with chronic spontaneous urticaria. Allergologia Et Immunopathologia, 53(4), 7–13. https://doi.org/10.15586/aei.v53i4.1443