Total Glucosides Of Paeony Combined With Traditional Disease Modifying Antirheumatic Drugs For Rheumatoid Arthritis:A Systematic Review

Objective:To evaluate the efficacy and safety of the combination of total glucosides of paeony(TGP)and traditional disease modifying antirheumatic drugs(DMARDs)in the treatment of rheumatoid arthritis(RA).Methods:A systematic literature search was performed,using Pubmed,Embase,Cochrane Library,Wanfang database,Weipu database,CNKI(up to January 2017 for all resources above),to search any language publications of randomized controlled trials(RCT)about the combination of TGP and traditional DMARDs treating RA.The participants were patients with RA,both sexes,any race,age ?18 and treatment duration?12weeks.The primary outcomes were ACR20/50/70.Secondary outcomes were tender joint count(TJC),swollen joint counts(SJC),C-reactive protein(CRP),erythrocyte sedimentation rate(ESR),etc.The safety outcomes were adverse events(AEs),toxicity-related withdrawals and total withdrawals.Two reviewers independently identified the included trials,evaluated bias risk and extracted relevant data.The Cocharane collaboration's Review manager 5.3 software was used for data analysis.Results: Twenty two RCTs met the inclusion criteria.They compared TGP plus traditional DMARD(s)with the same traditional DMARD(s).All RCTs treated the patients with oral TGP.Traditional DMARD(s)used in these RCTs were leflunomide(LEF)(5 RCTs),methotrexate(MTX)(9 RCTs),MTX and LEF(6 RCTs),MTX and hydroxychloroquine(HCQ)(1 RCT),and sulfasalazine(SSZ)(1 RCT),respectively.All RCTs were of high bias risk.No RCT used placebo.Only one RCT mentioned blinding on patients.Others did not specify any blinding measures.Therefore,blinding was judged as high risk bias for all trials.The information of randomization,allocation concealment and result data completeness was unclear in 15,22 and 19 RCTs,respectively.Seven studies did not report some outcomes planned in study protocol and were of high risk bias in selective reporting.Meta analysis showed that TGP plus traditional DMARD(s)were superior to the same traditional DMARD(s)in all primary outcomes.And the difference was statistically significant between the two groups.The RRs(95%CI)o f ACR20,ACR50,ACR70 were 1.16(1.02,1.31),1.32(1.09,1.60)and 1.38(1.01,1.89),respectively.TGP plus traditional DMARD(s)were superior to the same traditional DMARD(s)in some secondary outcomes including CRP,ESR,the duration of morning stiffness,SJC,patients pain VAS and patient global assessment(PGA)VAS.The difference was statistically significant between the two groups.The MDs(95%CI)of CRP,ESR,the duration of morning stiffness,SJC,patients pain VAS(0-100,the following VAS being the same)and Ph GA VAS were-5.84(-8.76,-2.92)mg/L,-3.52(-5.90,-1.14)mm/h,-0.11(-0.22,-0.01)h,-1.34(-2.45,-0.23),-6.6(-10.76,-2.46)and-8.67(-16.38,-0.96),respectively.No significant difference was found between TGP plus traditional DMARD(s)group and the same traditional DMARD(s)group in other secondary outcomes.AEs were significantly fewer in TGP plus traditional DMARD(s)group than in the same traditional DMARD(s)group.RR(95%CI)was 0.56(0.45,0.68).Conclusion: Comparing with the same traditional DMARD(s),TGP plus traditional DMARD(s)might get higher ACR20/50/70.Moreover,TGP plus traditional DMARD(s)might be more advantageous in CRP,ESR,the duration of morning stiffness,SJC,patient pain VAS and Ph GA VAS.Adding TGP to traditional DMARD(s)might decrease AEs.