Systemic Review Of Effects And Safety Of Sinomenine In Treatment Of Rheumatoid Arthritis

Objective:To evaluate the efficacy and safety of sinomenine(SIN)in the treatment of rheumatoid arthritis(RA).Method: We search the Pubmed、Embase、Cochrane Library、CBM、Wangfang database and CNKI(all up to April,2020)to discover and select the randomized controlled trials(RCTs)that involved the efficacy and/or safety of SIN in the treatment of RA.The participants were patients with RA.The primary outcomes were ACR20/50/70.The secondary outcomes included OR(overall response)which was defined as≥30% mean improvement in duration of morning stiffness,grip strength,C-reactive protein(CRP),rheumatoid factor(RF),DAS28,duration of morning stiffness,grip strength,swollen joint count(SJC),tender joint count(TJC),erythrocyte sedimentation rate(ESR),RF and CRP,safety outcome included adverse events and withdrawals.Two reviewers independently identified the included trials,evaluated risk of bias and extracts data.We use the Review manager software 5.3 to analyze data.Result:A total of 34 RCTs(n=3030)were included in this study.Seven compared SIN with traditional synthetic antirheumatic drug(csDMARD),which included methotrexate(MTX),leflomide(LEF),salazosulfopyridine(SASP)and penicillamine.Among them only 2 RCTs(n=244)reported primary outcomes,showing no significant difference between SIN and LEF in ACR20,ACR50,ACR70.In terms of secondary outcome indicators,there was no significant difference between SIN and csDMARD in OR,morning stiffness duration,SJC,ESR and RF.The incidence of adverse reactions and abnormal liver function were lower in SIN than in csDMARD group.Because the sample size of the included studies was small and most of them were non-blinding studies which had high risk of bias,more high-quality studies are needed to compare SIN with csDMARD.RCTs compared SIN with blank on the basis of csDMARD(s)in the treatment of RA.Among them 14 RCTs compared the SIN+MTX with MTX.In terms of primary outcomes,2 RCT(n=178)showed that the ACR20 of SIN+MTX was better than that of MTX,and 3 RCT(n=218)showed more ACR50 by adding SIN on the basis of MTX or MTX+LEF.In terms of secondary outcome,OR,DAS28,morning stiffness duration,grip strength,SJC,TJC,ESR,RF and CRP were better in SIN than in blank group.There was no significant difference in the incidence of adverse reactions and liver function damage.Four RCTs compared SIN+reduced dosage of MTX with MTX.They did not report primary outcome.In terms of secondary outcome indicators of OR,morning stiffness time,grip strength,SJC,TJC,ESR,CRP,etc.,no significant difference was found between these two intervention groups.The incidence of adverse reactions was lower in the group of SIN+reduced dosage of MTX.Conclusion: Limited evidence suggest that SIN and LEF might obtain similar ACR20 and ACR50,and SIN and csDMARD have the similar benefits of SIN and LEF in terms of secondary outcome indicators.Adding SIN on the basis of csDMARD could benefit in ACR20,ACR50,OR,DAS28,morning stiffness duration,grip strength,SJC,TJC,ESR,RF and CRP without significant increase of adverse reactions.Compared with MTX,reduced dosage of MTX had similar benefits in terms of secondary outcomes and fewer adverse reactions.