| ObjectiveChronic urticaria is a common disease in dermatology.At present,the second-generation antihistamines are recognized as the first-line drugs for the treatment of chronic urticaria at China and abroad.In the European guidelines for urticaria,omalizumab is a second-line treatment for chronic urticaria,but some patients with chronic urticaria do not respond to treatment with omalizumab.In Chinese guidelines for the treatment of chronic urticaria,third-line treatment is an immunosuppressive agent represented by Tripterygium glycosides and cyclosporine.Cyclosporine is also considered to be an alternative third-line immunosuppressive agent for the treatment of chronic urticaria in the European guidelines for urticaria,while azathioprine and methotrexate are recommended.However,there is no clear comparison on the effective rate,adverse reactions and recurrence rate of these four immunosuppressive agents in the treatment of patients with chronic urticaria.Tripterygium glycosides is one of the traditional Chinese medicine extracts with representative and therapeutic potential in China,which has significant effects and immunomodulatory effects and is widely used in clinical practice.A number of studies have shown that Tripterygium glycosides combined with antihistamines have fair efficacy in the treatment of chronic urticaria.Therefore,reticular meta-analysis was used to compare the efficacy and safety of Tripterygium glycosides,methotrexate,cyclosporine,and azathioprine combined with antihistamines in the treatment of chronic urticaria,in order to understand the order of the effective rate and incidence of adverse reactions of the four immunosuppressive agents and provide reference and evidence-based medical evidence for the clinical treatment of chronic urticaria.MethodsThe search strategy was determined according to the study objectives,and all published literatures related to immunosuppressive agents combined with antihistamines in the treatment of chronic urticaria from the establishment date to December 31,2021 were searched by computer in the American Full-text Database（Pub Med）,Cochrane library and Chinese Biomedical Literature Database（CBM）,Chinese Science and Technology Journal Database（VIP）,Knowledge Infrastructure（CNKI）,and Wanfang Database,and all literatures were screened.All literatures needed to meet both the inclusion criteria and exclusion criteria,and the literature quality of the selected articles was analyzed using the Cochrane Risk Assessment Tool.At the same time,the data in the literatures were extracted,including basic information,intervention measures,number of cases in the treatment group,effective number,number of patients with recurrence,adverse reactions,outcome indicators,follow-up time,etc.Finally,reticular meta-analysis was performed on all data using R 4.1.2 statistical software.ResultsA total of 58 randomized controlled trials（RCTs）with a total of 5528 patients,including 5 interventions,were included,with the overall clinical response rate as the primary outcome measure and the incidence and recurrence rate of adverse reactions as secondary outcome measures.Odds ratio（OR）and 95% confidence intervals（95% CI,Confident intervals）were used as effect measures.In terms of clinical response rate,58 articles contained a total of 5 interventions,of which（1）Tripterygium glycosides combined with antihistamines,methotrexate combined with antihistamines,cyclosporine combined with antihistamines and azathioprine combined with antihistamines had better efficacy than antihistamines.（2）There was no significant difference in the effective rate between Tripterygium glycosides combined with antihistamines,methotrexate combined with antihistamines,cyclosporine combined with antihistamines and azathioprine combined with antihistamines.Overall,the clinical response rate of immunosuppressive agents combined with antihistamines is higher than that of antihistamines.UAS7 analysis: The included literatures were analyzed according to UAS7 efficacy evaluation criteria,and 4 interventions were ranked probabilistically: cyclosporine combined with antihistamines,azathioprine combined with antihistamines >Tripterygium glycosides combined with antihistamines >methotrexate combined with antihistamines,antihistamines.Incidence of adverse reactions: Four interventions were included in the 41 included articles,namely,Tripterygium glycosides tablets combined with antihistamines,methotrexate combined with antihistamines,cyclosporine combined with antihistamines,and azathioprine combined with antihistamines.One control measure is antihistamines.In terms of adverse reactions,a total of 41 studies in the included literatures reported the occurrence of adverse reactions,including 4 groups of intervention drugs and 1 group of control drugs,which were Tripterygium glycosides combined with antihistamines,methotrexate combined with antihistamines,cyclosporine combined with antihistamines and azathioprine combined with antihistamines.Because the reticular meta-analysis results showed that the incidence of adverse reactions of methotrexate combined with antihistamines was lower than that of cyclosporine combined with antihistamines and azathioprine combined with antihistamines,there was no significant difference in pairwise comparisons between the other interventions.Because most of the adverse reactions mentioned in the 41 included literatures were gastrointestinal reactions or nervous system reactions,which could be relieved spontaneously without special treatment,the probability of adverse reactions was no longer ranked.Recurrence rate: 26 of 58 included literatures mentioned the number of patients with recurrence,of which the interventions in25 literatures were Tripterygium glycosides combined with antihistamines and antihistamines,and the interventions in only one literature were cyclosporine combined with antihistamines and azathioprine combined with antihistamines.Since there was no direct comparison between the two groups of interventions,a reticular meta-analysis could not be used,but because there were many literatures on Tripterygium glycosides combined with antihistamines included,we used Review Manager 5.4 to perform a direct meta-analysis and could see that the long-term efficacy of Tripterygium glycosides combined with antihistamines was better than that of antihistamines.Conclusion1.Compared with antihistamines,immunosuppressive agents combined with antihistamines are effective and safe in the treatment of chronic urticaria.2.Cyclosporine,azathioprine combined with antihistamines in the treatment of chronic urticaria may be a better effective combination of four immunosuppressive agents combined with antihistamines in the treatment of chronic urticaria.However,due to the small number of clinical studies and the fact that all included literatures were in English,with certain regional differences,it has certain instability,so clinicians and researchers may be required to carry out high-quality multi-center large-sample clinical study or laboratory study subsequently to verify and support the results of this analysis.3.Because most of the literatures included in this study are Tripterygium glycosides combined with antihistamines in the treatment of chronic urticaria,which is because Tripterygium glycosides are Chinese patent medicines,which are medical characteristics in China,and Tripterygium glycosides are only third-line therapeutic drugs in the guidelines for urticaria in China,and their related research literatures may have certain regional bias,and the results of this study also have certain regional and era limitations,and it is expected that more and better studies will supplement or criticize this study in the future. |
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