Chinese herbal formulas as adjuncts to antihistamines in chronic spontaneous urticaria: a network meta-analysis of efficacy, recurrence, and safety

Background Chronic spontaneous urticaria (CSU) presents treatment challenges despite second-generation antihistamines (sgAHs) serving as the first-line therapy. Purpose The aim of this network meta-analysis is to systematically evaluate the efficacy hierarchy and safety profile of classical traditional Chinese medicine (TCM) formulas used as adjuncts to antihistamines. Methods We systematically evaluated 50 randomized controlled trials involving 5,814 patients using both Bayesian and frequentist network meta-analyses (NMAs) to compare the efficacy, recurrence, and safety of sgAHs alone or in combination with classical TCM formulas. The primary outcome was clinical improvement based on the Symptom Score Reducing Index (SSRI), with secondary outcomes including recurrence rates and adverse events (AEs). Risk of bias was assessed using RoB 2.0, and evidence certainty was evaluated using the CINeMA framework. Bayesian and frequentist NMA approaches were employed. Sensitivity analyses were conducted based on the study quality and prescription modifications. Results Most combination regimens of classical TCM formulas were superior to antihistamine monotherapy for both SSRI ≥90% and ≥60% outcomes. Combinations involving Danggui Yinzi, Yupingfeng powder, and Guizhi decoction consistently ranked among the top in terms of efficacy. Among these regimens, loratadine or ebastine combined with Danggui Yinzi demonstrated the most pronounced reduction in recurrence risk, with the effect being more evident in the long-course subgroup (>12 weeks). Certain combination regimens, such as cetirizine combined with Danggui Yinzi and loratadine combined with Guizhi decoction , were associated with a reduced risk of AEs. However, no evaluated treatment showed a statistically significant advantage over cetirizine monotherapy in reducing IgE or IL-4 levels. The certainty of evidence for efficacy outcomes was predominantly moderate, whereas the overall certainty for safety outcomes was relatively low. Conclusion In CSU management, classical TCM formulas, particularly Danggui Yinzi, Yupingfeng powder, and Guizhi decoction, may improve remission and reduce recurrence when combined with sgAHs without increasing the incidence of AEs. Further high-quality head-to-head trials are needed to confirm these findings. Systematic Review Registration https://www.crd.york.ac.uk/PROSPERO , identifier CRD420251022634.