Abstract: 【Abstract】 Objective To explore predictive factors for the efficacy of omalizumab in the treatment of refractory chronic spontaneous urticaria （CSU）. Methods Totally, 40 patients with refractory CSU treated with omalizumab were enrolled from Department of Dermatology, the Second Affiliated Hospital of Soochow University from 2019 to 2021. Before treatment, clinical data including the urticaria activity score over 7 days （UAS7） and dermatology life quality index （DLQI） were collected; venous blood samples were collected for the detection of total immunoglobulin E （IgE） antibodies, eosinophil counts and basophil counts, anti-thyroid peroxidase （TPO） IgG antibody levels, mean platelet volume, as well as C-reactive protein （CRP）, D-dimer, complements C3 and C4, interleukin （IL）-2, IL-4, IL-6, IL-10, IL-17A, tumor necrosis factor （TNF）-α and interferon （IFN）-γ levels, and percentages of CD4+ T cells and CD8+ T cells; meanwhile, the autologous serum skin test （ASST） was performed. After 12-week treatment with omalizumab, 40 CSU patients were divided into well-responding group and poorly-responding group according to the UAS7 score, and the above laboratory indicators were compared between the two groups. For continuous variable indicators with significant differences, the accuracy of prediction and optimal cut-off values were determined by using the receiver operating characteristic （ROC） curve; for categorical variable indicators with significant differences, the sensitivity and specificity for the prediction of poor clinical response to omalizumab were calculated; correlations among the above indicators were analyzed by Pearson correlation analysis. Results After 12-week treatment with omalizumab, 28 CSU patients responded well to omalizumab, and 12 responded poorly. Before treatment, the poorly-responding group showed significantly increased proportions of patients with eosinopenia （6/12）, basopenia （7/12）, decreased C3 （6/12）, decreased C4 （6/12）, positive anti-TPO IgG antibodies （5/12） and low total IgE levels （8/12）, increased proportion of CD4+ T cells （71.13% ± 3.26%）, and increased IL-17A levels （27.16 ± 9.75 pg/ml） compared with the well-responding group （14.3%, 10.7%, 14.3%, 7.1%, 10.7%, 14.3%, 60.33% ± 5.12%, 19.24 ± 10.84 pg/ml, respectively; all P < 0.05）, but decreased IL-6 levels compared with the well-responding group （t = 5.75, P < 0.05）. According to the ROC analysis and calculation of sensitivity, specificity and accuracy, the above indicators showed high accuracy in predicting therapeutic effect of omalizumab, and the optimal cut-off values of IL-6, IL-17A, and CD4+ T cell proportion were 8.672 pg/ml, 23.415 pg/ml, and 67.95%, respectively. In addition, the IL-6 level was significantly positively correlated with the total IgE level in CSU patients at baseline （r = 0.43, P = 0.006）. Conclusion Before the selection of omalizumab for the treatment of refractory CSU, there is a need to detect the eosinophil and basophil counts, levels of complements C3, C4, anti-TPO IgG antibodies, total IgE, IL-17A and IL-6, and CD4+ T cell proportions to predict therapeutic effect of omalizumab, so as to determine whether omalizumab is suitable for the patients.

Key words: Urticaria, Chronic spontaneous urticaria, Omalizumab, Efficacy, Predictors, Cytokines