Systematic Review Of Randomized Controlled Trials Investigating Iguratimod For Treatment Of Rheumatoid Rrthritis

Objective: To evaluate the efficacy and safety of iguratimod for thetreatment of rheumatoid arthritis (RA).Methods: Randomized controlled trials (RCT) about iguratimod for RA inany language were sought using the following sources: Pubmed,CochraneLibrary, CENTRAL, Embase, CBM, CNKI, Weipu database, Wanfang database(upto January2013).Two reviewers independently identified the eligiblestudies, assessed their risk of bias and extracted data. RevMan software5.1was used for meta-analysis.The primary outcomes were ACR20/50/70.There were10secondary outcomes, including rest pain, morning stiffness,tender joint count etc. The safety outcomes were adverse events,toxicity-related withdrawals and total of withdrawals and drop-outs.Results: Six RCTs met the inclusion criteria. Two of them were reportedonly as abstract and result data was imcomplete.The dosage of iguratimodwas25mg/d or50mg/d with the duration of treatment ranged from8weeksto28weeks.These RCTs compared iguratimod with placebo,SSZ,MTX ornimesulide. One of them was of high quality. Others were not.Amongthem,2,1and3RCTs did not offer detail information of randomization,allocation concealment and blinding,respectively.We were unable toassess the risk of bias of those two RCTs with only abstract report.FourRCTs compared iguratimod with placebo.One of them had only abstractreport.The results showed that iguratimod was superior to placebo in boththe primary and secondary outcomes. The RRs of ACR20,ACR50and ACR70were2.35(1.87,2.96),2.86(1.87,4.39) and4.75(2.08,10.84), respectively.There was no statistical difference in the rates of adverse events andtoxicity-related withdrawals between the iguratimod group and theplacebo group. The rate of total of withdrawals and drop-outs was lowerin the iguratimod group. One trial compared50mg iguratimod group with25mg iguratimod group. The results showed50mg group was superior to25mg group in the ACR20outcome, but nonsuperior in the ACR50and ACR70outcomes.The RRs of ACR20,ACR50and ACR70were1.57(1.16,2.12),1.25(0.78,1.99) and0.99(0.49,2.02).The50mg group was also found to have better effect inthe outcomes of rest pain, patient’s global assessment, physician’sglobal assessment and ESR.There was no statistical difference in thesafety outcomes between the two groups.Two trials compared iguratimodwith SSZ and MTX respectively. There was no statistically significantdifference between iguratimod and SSZ group. RRs of ACR20and ACR50were1.09(0.88,1.36) and0.98(0.67,1.44). However, the iguratimod group hadlower ACR response rate compared to MTX although the difference was notstatistically significant.The RRs of ACR20,ACR50and ACR70were0.93(0.79,1.08),0.82(0.65,1.03) and0.84(0.57,1.23).In the safety outcomes therewas no statistical difference between the iguratimod group and SSZ groupas well as between the iguratimod group and MTX group.Two RCTs comparediguratimod with nimesulide.Each reported that ACR20and ACR50werestatistically higher in the iguratimod group than in the nimesulide grouprespectively.There was no statistical difference in ACR70and safetyoutcomes between the two groups.The result data of these two RCTs wasimcomplete and were not included in our analysis.Conclusion: Compared to placebo, iguratimod might increase the ACRresponse rate in RA patients and benefit them in secondary outcomes.50mggroup was superior to25mg group.Higher rates of adverse events andtoxicity-related withdrawals were found in iguratimod than in placebogroup although the difference was not statistically significant.Comparison of iguratimod and SSZ showed similar efficacy and safety withSSZ.The efficacy and safety of iguratimod in comparison with nimesulideand MTX in the treetment of RA needs more evidence of RCTs.