Anti-TPO IgG/Total IgE Ratio: Biomarker for Omalizumab Response Prediction in Chronic Spontaneous Urticaria

Background: According to recently published data, low total IgE, elevated IgG-anti-TPO, and a high IgG-anti-TPO/total IgE ratio are good biomarkers for subtype IIb autoimmune chronic spontaneous urticaria (CSU), which is frequently refractory to antihistamines and omalizumab.

Objectives: The aim of the study was to evaluate IgG-anti-TPO/total IgE ratio's utility in omalizumab response prediction.

Methods: Retrospective study of CSU patients treated with omalizumab at a UCARE between January 2009 and February 2022. Patients were grouped according to response in the first 16 weeks of treatment: responders UAS7 < 7 versus partial/non-responders UAS7≥7. Total IgE, IgG-anti-TPO, and IgG-anti-TPO/total IgE ratio were compared. Other inflammatory biomarkers - eosinophils, basophils, C-reactive protein, erythrocyte sedimentation rate, and d-dimer - were analyzed.

Statistical analysis: SPSS® (v25.0), p < 0.05 statistically significant.

Results: Total of 175 patients, 140 (80%) women, median age 49 [9-88] years, mean CSU duration pre-omalizumab 5.6 ± 8.2 [0-54] years, omalizumab duration 3.2 ± 2.5 [0-12] years. 116 (66%) had angioedema, 77 (44%) inducible chronic urticaria, 60 (34%) atopy, 24 (14%) autoimmune disease. With omalizumab 300 mg q4 weeks, 69% were responders and 31% partial/non-responders. Although not reaching significant differences, mean total IgE values were lower and mean IgG-anti-TPO values were higher in partial/non-responders versus responders (152 vs. 242 kU/L, p = 0.207, and 38.3 vs. 25.7 U/mL, p = 0.408, respectively). A higher IgG-anti-TPO/total IgE ratio was significantly associated with poorer response to omalizumab (p = 0.040). A cut-off >0.154 increased 10 times the odd of poorer response [95% CI 4.62-22], AUC 0.872, p < 0.001, with 87.7% sensitivity, although the low specificity (22.4%) does not allow the assumption of response with values <0.154. Other laboratory biomarkers did not show significant differences between partial/non-responders versus responders.

Conclusions: A high IgG-anti-TPO/total IgE ratio was a good biomarker of poor response to omalizumab in our CSU cohort, with a cut-off >0.154 increasing 10 times the odd of poorer response.