Treatment Of Rheumatoid Arthritis With Combination Of Methotrexate And Tripterygium Wilfordii: Meta-analysis And System Biological Interpretation

Objective Extracts of Tripterygium wilfordii Hook F(TwHF),a traditional Chinese herbal medicine,have been widely used for the treatment of rheumatoid arthritis(RA)in combination with methotrexate(MTX)in China.However,the efficacy,safety and mechanisms of this MTX plus TwHF treatment remain unclear.In this thesis,we aim to evaluate the efficacy and safety of this treatment strategy by Meta-analysis,and then to examine the underlying mechanisms by system biological analysis.MethodsFor meta-analysis,a comprehensive search of database in both Chinese and English was performed.Data from the selected studies was extracted and analyzed according to certain standards.For system biology analysis,we searched the targets of TwHF from TCNMID,searched the RA related gene from OMIM,GAD and KEGG,and searched the targets of MTX and other RA drugs from DrugBank and Pharmainformatics Database.And then system biology analysis was performed to examine the biological implications.Results1.Six randomized controlled trials were included in final analysis with a total of 643 patients.All trials added TwHF(in the form of tripterygium glycosides)in the MTX based therapy.For the efficacy,the add-on of TwHF increased by 50%responder rates(RR 1.337,95%CI:1.188-1.505,P<0.001),and it also reduced swollen and tender joint counts,shorted the duration of morning stiffness,and decreased the erythrocyte sedimentation rate,the level of C-reactive protein and rheumatoid factor.For the safety,the add-on of TwHF did not increase the rate of adverse events(RR 0.824,95%CI:0.635-1.068,P = 0.143).2.System biological analysis showed that TwHF and MTX co-targeted lymphocyte proliferation pathway.In addition,TwHF targeted additional three unique pathways in immune system process(regulation of mononuclear cell,toll-like receptor TLR1:TLR2 signal pathway and regulation of interferon-gamma-mediated signaling pathway).Conclusion The MTX plus TwHF therapy may be a more effective and similar safe strategy for treatment of RA compared to MTX monotherapy,which is supported by system biological analysis.The long-term effect and safety of tripterygium wilfordii combined methotrexate need further research.