Baseline systemic inflammatory indices as predictors of treatment escalation in chronic spontaneous urticaria a cohort study

Abstract

Management of chronic spontaneous urticaria (CSU) remains challenging due to frequent patient refractoriness to high-dose H1-antihistamines, necessitating omalizumab therapy. At diagnosis, reliable and accessible biomarkers are critical to predict which patients will require treatment escalation. This study aimed to evaluate baseline hematological parameters and derive inflammatory indices for their capacity to predict maximum H1-antihistamine dose and subsequent need for omalizumab in a homogenous CSU cohort without major comorbidities. This single-center, retrospective cohort study included 185 adult CSU patients. Baseline inflammatory markers were analyzed relative to the primary outcome of omalizumab requirement and secondary outcome of intensity of antihistamine dose. Multivariate logistic regression and receiver operating characteristic analyses identified independent predictors and optimized cut-off values. Higher baseline levels of inflammatory markers, such as white blood cell count, neutrophils, neutrophil-to-lymphocyte ratio, systemic immune-inflammation index, and aggregate index of systemic inflammation (AISI), were significantly associated with the need for fourfold antihistamine dosing. Adjusted multivariate analysis identified AISI ≥ 346.8 (adjusted odds ratio [aOR] = 7.45) as an independent predictor of omalizumab requirement, while erythrocyte sedimentation rate (ESR) > 7.5 (aOR = 0.24) was identified as an independent protective factor against omalizumab requirement. As a standalone biomarker, AISI demonstrated an area under the curve (AUC) of 0.733 and a negative predictive value (NPV) of 96.4% at this threshold. In this cohort, baseline AISI was independently associated with omalizumab requirement and appears to be a promising marker that warrants external validation, whereas elevated ESR appears protective. Given the retrospective single-center design, these findings should be interpreted cautiously. A high NPV of the AISI cut-off suggests potential clinical utility for ruling out patients unlikely to require treatment escalation.