| Objective: To evaluate the efficacy and safety of the methotrexate(MTX)combined with hydroxychloroquine(HCQ)in the treatment of rheumatoid arthritis(RA).Methods: A systematic literature search was performed,using Pubmed,Cochrane Library,Embase,Wanfang database,CNKI,Weipu database(up to January 2018 for all resources above),to search any language publications of randomized controlled trials(RCT)about the combination of MTX and HCQ treating RA.The participants were patients with RA.The primary outcomes were ACR20/50/70,and overall response(OR)which was defined as ?30% mean improvement in tender joint score(TJS),swollen joint score(SJS),C-reactive protein(CRP),erythrocyte sedimentation rate(ESR),morning stiffiness,etc.The secondary outcomes were tender joint count(TJC),swollen joint counts(SJC),TJS,SJS,CRP,ESR,morning stiffiness,Physician global assessment(PhGA)VAS etc.The safety outcomes were adverse events(AEs),toxicity-related withdrawals and total withdrawals.Two reviewers independently identified the included trials,evaluated risk of bias and extracted relevant data.The Cocharane collaboration's Review manager 5.3 software was used for data analysis.Results: This systematic review included 23 RCTs with a total enrollment of 1,730 patients,10 studies comparing MTX+HCQ with MTX alone(n=727),7 with MTX+leflumetide(LEF)(n=480),5 with MTX+sulfasalazine(SSZ)(n=535)and 1 with MTX+HCQ+SSZ(n=116).(1)MTX+HCQ got more OR than MTX alone.RR(95% CI)was 1.19(1.11,1.27)and NNT was 6.88.In the outcomes of morning stiffness time,TJC,SJC,TJS,SJS and PhGA VAS,CRP,ESR,etc.MTX+HCQ was superior to MTX(P<0.05).The incidence of Aes in MTX+HCQ was lower than in MTX.RR was 0.67(0.48,0.93)and NNH was 14.3.(2)MTX+HCQ was inferior to MTX+LEF in OR and ACR50,The RRs were 0.83(0.76,0.92)and 0.60(0.43,0.84),respectively.NNTs were 6.16 and 4.79.No significant difference was found in ACR20.RR was 0.85(0.72,1.00).In SJC,pain,PGA VAS,CRP,ESR,MTX+HCQ was inferior MTX+LEF(P<0.05).The incidence of AEs was similar.(3)MTX+HCQ was superior to MTX+SSZ in OR.RR and NNT were 1.21(1.09,1.35)and 6.41,respectively.However in ACR20,the difference was not significant and RR was 1.14(0.9,1.44).MTX+HCQ was superior to MTX+SSZ in the duration of morning stiffness,MD was-20.46(-36.91,-4.02)min.The incidence of AEs was similar.(4)The ACR20 of MTX+SSZ+HCQ had a tend to be superior to MTX+HCQ,but did not reach statistical significance.RR was 0.78(0.61,1.00).In the duration of morning stiffness,TJC,and ESR,MTX+HCQ+SSZ was superior to MTX+HCQ.The MDs were 50.10(15.44,84.76)min?4.00(0.68,7.32)min and 9.30(2.18,16.42)min,respectively.The incidence of AEs was similar.Conclusion: Compared with MTX alone,MTX+HCQ has advantages in both OR and AEs.There is no evidence that the efficacy of MTX+HCQ is superior to MTX combined with any other DMARD.MTX+HCQ might be inferior to MTX+SSZ+HCQ in efficacy.AEs was similar in MTX+HCQ and in MTX combination with other DMARD(s).More studies of high quality are needed to verify the combination of MTX and HCQ for RA. |
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