D1.514 - Assessment of Serum Substance P Levels in Chronic Spontaneous Urticaria with Predominant Pruritus Refractory to H1-Antihistamines and Omalizumab

Substance P is a neuropeptide that activates cutaneous mast cells and modulates pruritus intensity in dermatologic conditions. However, its role and prognostic relevance in chronic spontaneous urticaria (CSU) remain unclear. 

Serum Substance P Levels (SSPL) were measured in four cohorts: (1) CSU with incomplete disease control at blood sampling (n=10; Group 1); (2) CSU with persistent pruritus, defined as an isolated UAS7 elevation driven by pruritus (mean 5.67, SD 4.97) despite H1-antihistamines and/or omalizumab (n=15; Group 2); (3) CSU with predominant pruritus in patients receiving/indicated for psychopharmacotherapy (n=24; Group 3); (4) pruritus of other causes (n=12; Group 4); and healthy controls (n=10). 

A total of 61 patients were included. Among them, 49 CSU patients were selected to derive a treatment-level–based cut-off potentially reflecting disease severity. An SSPL threshold of 18.863 pg/mL showed high sensitivity (94.1%; 16/17) and moderate specificity (56.3%; 18/32) for identifying patients who required omalizumab due to insufficient efficacy of antihistamines (p=0.000565).

SSPL were higher in Group 2 (24.55 [22.24–35.23]) than in controls (15.88 [10.61–25.32]; p=0.0213). A comparable increase was observed in Group 4 (23.85 [18.03–40.05]; p=0.0409). Groups 1 and 3 did not differ from controls: 23.07 [18.97–25.47] (p=0.4727) and 17.47 [15.78–21.40] (p=0.4384), respectively.

In CSU patients receiving omalizumab, SSPL was 23.54 [21.67–30.47] (n=17), higher than in CSU treated with H1-antihistamines and/or psychopharmacotherapy (18.32 [15.55–24.23]; p=0.00296) and higher than controls (p=0.0254).

Blood parameters were analyzed (eosinophils, basophils, leukocytes, ESR, CRP). To differentiate CSU subtypes (I, IIb), total IgE, IgG-anti-TPO, and IgG-anti-TG were assessed. SSPL correlated with CRP in all patients (p=0.0176) and within each group. 

High SSPL were found in persistent pruritus with pruritus-isolated UAS7 increases and in pruritus of other causes. SSPL showed no differences in patients treated with H1-antihistamines and/or psychopharmacotherapy. However, high SSPL were detected in patients receiving omalizumab and with elevated CRP. These patients have incomplete control primarily due to dominant pruritus, which may require different therapeutic approaches. Further analysis across additional urticaria phenotypes is planned to increase sample size and strengthen the evidence base.