The Effect of Placebo on Pruritus in Patients with Chronic Urticaria: A Systematic Review and Meta-Analysis of Randomized Placebo-Controlled Trials

BackgroundThe anti-pruritic effect of placebo in patients with chronic urticaria has gained increasing attention in clinical research. However, the extent of placebo effect and its influencing factors in the treatment of chronic urticaria are not well understood.ObjectiveThe objective of this systematic review and meta-analysis was to investigate the effect of placebo on pruritus in patients with chronic urticaria and to explore relevant influencing factors.MethodsPubMed, Embase, Web of Science, Cochrane Library, and PsycINFO were searched from inception to 10 July, 2024. Primary outcome included pruritus scores. The secondary outcomes focused on global symptoms and quality of life. Subgroup analyses and meta-regression analyses were conducted based on drug types, sample size, participants' age, and other variables. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system and a trial sequential analysis were employed to establish the reliability of evidence.ResultsA total of 65 eligible publications (including 67 randomized controlled trials) involving 10,704 patients with chronic urticaria were included. The pruritus scores decreased following placebo treatment (moderate evidence). In addition, favorable results were observed in global symptoms (moderate evidence) and quality of life (low evidence) after placebo treatment. Subgroup analyses indicated that the type of active medication in intervention groups was an influencing factor of placebo effect of pruritus. Meta-regression analyses demonstrated that the anti-pruritic effect of placebo was inversely correlated with sample size and positively correlated with participants' age. A trial sequential analysis provided further support for the anti-pruritic effect of placebo.ConclusionsA substantial improvement of pruritus after placebo treatment was observed in patients with chronic urticaria. The anti-pruritic effect of placebo varied with sample size, participants' age, and type of active medication used. Future research should further investigate the effect size of placebo and clarify the potential mechanism.PROSPERO RegistrationThe protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO) as CRD42023482608.