Efficacy And Safety Of 24-week Treatment With Iguratimod As The First-line CsDMARD For Patients With Rheumatoid Arthritis And Early Rheumatoid Arthritis:A Prospective,Cohort Study

ObjectiveRheumatoid arthritis(RA)is a chronic,synovitis-dominated autoimmune disease of unknown etiology that can lead to progressive bone destruction,resulting in joint deformity and functional loss.Epidemiological surveys show that there are about 5 million patients with RA in China.Chinese rheumatology started later than Europe and the United States,but most of the original drugs come from foreign giants.So the development of original drugs is particularly important for the progress of rheumatology discipline in China.As the first new anti-rheumatic drug with independent intellectual property rights jointly developed by China and Japan,the successful development and marketing of iguratimod(IGU)is important for the treatment of rheumatic diseases.The optimal first-line treatment for patients with early rheumatoid arthritis(ERA)and rheumatoid arthritis has not been determined.The aim of this study was to observe the efficacy and safety of 24-week treatment with IGU as the first-line conventional synthetic disease-modifying antirheumatic drug(csDMARD)for patients with rheumatoid arthritis and early rheumatoid arthritis and to explore the clinical characteristics of IGU and the optimal combination of IGU to contribute to real-world studies of the domestic original drug.MethodsPatients with rheumatoid arthritis attending the rheumatology clinic of Qilu Hospital of Shandong University from November 2016 to September 2019 were collected and evaluated by the 1987 ACR rheumatoid arthritis criteria the 2010 ACR/EULAR criteria,and the 2012 Chinese early rheumatoid arthritis criteria.Patients who met the 1987 ACR criteria were included in the RA group,and those who did not meet the 1987 ACR criteria but met the 2010 ACR/EULAR criteria and/or met the 2012 Chinese early rheumatoid arthritis criteria were included in the ERA group.All enrolled patients were given IGU treatment with or without methotrexate(MTX),hydroxychloroquine sulfate(HCQ),and prednisone(Pred)according to their baseline disease activity,previous drug response,and tolerability.Patients’age,gender,duration of disease(months),duration of morning stiffness(minutes),blood count,Erythrocyte sedimentation rate(ESR),C-reactive protein(CRP),Swollen joints of 28 counted(SW28),Tender joints of 28 counted(T28),Health Assessment Questionnaire(HAQ),previous medication use,previous medical history,joint ultrasound score,joint X-ray score were recorded at baseline.The patients’ morning stiffness time,blood count,ESR,CRP,T28,SW28,blood count,liver and kidney function,and urine count were recorded at 4,12,and 24 weeks,and the efficacy indexes such as disease activity of 28 joints(DAS28),ACR20/50/70,Boolean remission,EULAR response,and adverse events(AE)were calculated,and the clinical characteristics and treatment response of patients in both groups were analyzed.Results1.Two hundred and seventeen patients completed the 24-week study.At 24 weeks,24(54.6%)and 85(49.1%)patients in the ERA and RA groups achieved low disease activity or clinical remission on DAS28-ESR,32(72.7%)and 133(76.9%)reached ACR20,18(40.9%)and 87(50.3%)achieved ACR50,8(18.2%)and 43(24.9%)achieved ACR70,16(36.4%)and 56(32.4%)achieved Boolean remission,and 35(79.6%)and 137(79.2%)achieved good or moderate EULAR response.2.The IGU regimen demonstrated good efficacy over the course of treatment,with significant decreases in all disease activity indicators from baseline.The improvement in symptomatology was more pronounced during ERA and RA treatment compared to the improvement in serum inflammatory indicators such as ESR and CRP.The best improved indicator in the ERA group was SW28(mean improvement rate 68.5%),followed by SDAI(51.1%),T28(46.5%),and CDAI(46.7%),respectively.The improvement rate of the above four indicators was significantly better than that of ESR.The best improved index in the RA group was SW28(74.6%),followed by CDAI(64.3%)and T28(62.3%),respectively,and the improvement of the three physicians’ indexes was better than that of CRP(12.7%)and ESR(11.3%)(p<0.05).3.Repeated-measures ANOVA found that there were differences in DAS28-ESR,SDAI,CDAI,HAQ,PGA,and CRP changes between ERA and RA patients at 24 weeks.ERA group has mild disease activity and slow improvement,while RA group has severe baseline disease and rapid improvement.There was no significant difference in the outcome of each index between the two at 24 weeks.4.It was found that middle and old age,high RF,high DAS28-ESR in baseline were independent risk factors for patients not achieve DAS28-ESR REM+LDA,and previously not used of IGU was an independent protective factor for patients with DAS28-ESR criteria.5.After adjusting age and gender,it was found that the improvement of SDAI and CDAI in patients with MTX combination was better than that that in non-MTX-combination patients,and the improvement of SDAI and CDAI in patients with Pred combination was also better.Although the improvement in patients with HCQ combination had no significant benefit,the attainment rate of ACR70 was higher in patients who combined HCQ in the dosing regimen at 24 weeks.6.The safety of the IGU-based csDMARD regimen was good.Thirteen(22.03%)and sixty-one(26.64%)adverse events were observed in the ERA and RA groups,and no serious adverse events were observed,with a safety profile superior to that of the Japanese phase Ⅳstudy.ConclusionERA and RA patients have different clinical characteristics:ERA patients have early age of onset,short disease duration,low baseline disease activity,and shorter DAS28-ESR attainment time.Early treatment of ERA is recommended to facilitate early attainment.RA patients have late age of onset,long disease duration,relatively heavy baseline disease activity,and longer DAS28-ESR attainment time than RA,but the disease activity decreases rapidly after given adequate treatment in RA group.Therefore,treatment with IGU is safe and effective in patients with ERA and RA,and improves joint symptoms better than inflammatory parameters.IGU in combination with MTX or Pred improves clinical activity without increasing the risk of adverse events,while combination with HCQ improves ACR70 after 24 weeks.The combination of IGU with LEF or HCQ may increase the risk of adverse events and combination with LEF increases the risk of discontinuation.Therefore,this study recommends IGU in combination with MTX or Pred,instead of LEF.For the combination of IGU and HCQ,the incidence of adverse events should be fully evaluated.