Efficacy And Safety Of Iguratimod In The Treatment Of Early Rheumatoid Arthritis For 6 Months

Research purposeRheumatoid arthritis(RA)is a common autoimmune disease,with multiple joint pain and resulting in joint deformity and loss of function.In recent year,that RA diagnostic standard has been continuously update,the ACR classification standard in 1987,although high in accuracy,has made it possible for patients to be diagnosed to miss an early treatment opportunity;new diagnostic criteria proposed by ACR/EULAR in 2010 try to discover early RA,after which national scholars attach importance to the screening of ERA courses with a course of less than 24 months,And suggest a very early RA(VERA)concept with a symptom less than 3 months.In 2012,the Professor Li Zhang established the ERA "Chinese Standard",and the sensitivity accuracy was recognized by the peer.In recent years,several databases have conducted systematic follow-up studies of ERA,and there are no large-scale data and treatment strategies in our country.The concept of the RA-standard treatment is to adjust the treatment plan according to the disease activity,because the early diagnosis and treatment of the early diagnosis and treatment of the RA is emphasized by the expert:consensus at home and abroad due to the early and more easy joint destruction of the RA,and the·'Treatment of Window"in the three months of the onset of the disease is controlled to reduce the disease progression and deterioration,blocking joint failure and achieving a higher withdrawal response rate.Within a period of 12 months and within 3 months,VERA is the prime time to increase the response rate and to reduce bone destruction.At home and abroad,the high-risk predictive factors for RA joint destruction included Anti-CCP antibodies,Rheumatoid Factor(RF)positive and bone destruction at baseline,and the first two antibodies were also highly sensitive to ERA diagnostic sensitivity.High-frequency ultrasound can detect the thickness and blood flow of the joint synovial membrane,so the antibody detection and the ultrasound technique are the powerful weapon for the early diagnosis,treatment selection and curative effect evaluation of the ERA and the VERA.However,in clinical practice,it has been found that there are differences in the activity,response and prognosis of different types of ERA(such as whether the antibody is positive,whether the inflammatory index level is parallel to the synovial disease of the joint,etc.).Some patients even fluctuate repeatedly and can only be diagnosed as Undifferentiated Arthritis(UA)and delay treatment.Therefore,there has been a lack of unified treatment intervention and follow-up for these different subtypes at home and abroad,and the clinical indexes such as different phenotypes,disease activity,predictive factors,treatment response and the level of immune inflammation in patients were analyzed.The correlation of specific gene expression has not yet established big data and individualized targeted therapy strategies in patients with ERA and VERA.Iguratimod(IGU)is a new type of small molecule drug(DMARDs),which has a unique mechanism of action,such as inhibiting the release of inflammatory factors,directly inhibiting b cells and reducing the level of autoantibodies.Down-regulation of cellular immunity induced negative regulation of immunity and reduction of bone loss.At the same time,IGU is a derivative of nimesulide,which can quickly relieve the symptoms of arthritis patients,so IGU is a new drug with both DMARDs and non-steroidal anti-inflammatory drug(NSAIDs)function.Clinical practice has found that the response of arthritis patients to IGU is individual difference.Because the clinical manifestations of er are not typical and the progress is not uniform,the inflammatory indexes and antibodies can not fully reflect the joint lesions,which makes people hesitate to reduce the withdrawal of dmards in the face of different subtypes of ERA,At present,there are few reports of IGU in the treatment of ERA and VERA.It is worth exploring whether UA and VERA patients can use IGU single drug to achieve rapid control and successfully reduce it to drug-free remission.Therefore,according to the stratification of disease activity and prognostic factors,igu single drug and MTX and other DMARDs are used to treat UA,ERA and RA,with different phenotypes in order to increase and decrease the drug in order to meet the standard treatment,which will certainly further understand the clinical characteristics of this new drug.Immune mechanism and drug target are beneficial to the basic research of era in China,the formulation of clinical diagnosis and treatment plan,and the further improvement of cost-effectiveness ratio of Pharmacoeconomics.Research methodA total of 232 patients with the Department of Rheumatology in Qilu Hospital of Shandong University were collected and their clinical characteristics were recorded.according to the poor prognosis factors and the disease activity of the baseline period,the treatment for 6 months with the igu single agent and/or the combination of the methotrexate(mtx),the hcq,the hormone(pred)and the other dmeds is adopted to observe the change of the state of the disease,and the ascending step or the step-down treatment is adopted,And finally the condition control is achieved.The clinical indexes such as tenderness(T28)/swollen joint(sw28),erythrocyte sedimentation rate(ESR)and c-reactive protein(CRP)were recorded during each follow-up.Each patient needed to do health assessment questionnaire(HAQ)The responses to DAS28-ESR,SDAI,CDAI,GH-VASand ACR20 remission and eular remission were calculated,the use of IGU and accompanying drugs was recorded,and the clinical efficacy and adverse reactions were evaluated.According to the manifestations of arthritis at baseline,serological indexes and imaging findings,the previous drugs were divided into different diagnostic subgroups and divided into RA group(in accordance with the 1987 ACR classification standard).ERA group(according to 2010 ACR/EULAR classification standard and 2012 ERA Chinese standard but not 1987 ACR classification standard,course of disease?24 months)and UA group(does not meet 2010 RA standard and 2012 ERA Chinese standard,and the course of disease?24 months)and different subtypes,It was divided into high antibody type(high titer Anti-CCP antibody or RF),high inflammatory type(Anti-CCP antibody and RF negative,but ESR and/or CRP significantly increased)and local joint type(Anti-CCP antibody and RF negative,ESR and CRP increased not significantly.However,ultrasound/MRI imaging showed typical synovitis of wrist,mcp,pip,toes and ankle joints.According to the history of not receiving any dmards drugs in the past,the rest of dmards were replaced with Elamod after ineffective treatment,the rest of dmards were replaced with IGU after treatment with imtolerance,and the recurrence after withdrawal was changed to IGU.According to sex,age,duration of disease,baseline morning stiffness grade,baseline haq grade,baseline CRP grade and baseline DAS28-ESR grade,they were grouped according to sex,age,duration of disease,baseline morning stiffness grade,baseline CRP grade and baseline DAS28-ESR grade.In the follow-up,a total of 165 patients had completed 6-month clinical observation(F-group)due to the withdrawal or lost-to-follow-up of the patient due to the efficacy,safety and economic reasons,and the pre-and post-treatment indexes were repeated with the spss 20 for general linear model,and the single-factor analysis of variance,The statistical methods such as the independent sample t test and the chi-square test were used to compare the baseline disease activity,the efficacy and the drug response,and the treatment protocol data analysis.Of the 67 patients(UF group)who did not complete the 6-month follow-up,165 patients in the same Fgroup were diagnosed with baseline characteristics,the cause of the entry,the prognostic factors,the baseline morning stiffness,the baseline CRP,the baseline HAQ,the baseline DAS28-ESR,the initial treatment protocol,and the entire treatment regimen,The clinical characteristics of the patients with iu-sensitive population,poor compliance and non-tolerance were found by multi-dimensional contrast analysis,such as the adverse reaction and the reason of the withdrawal.Research productionF group:the indexes affecting the activity of the baseline disease were age(>60y),course of disease(diagnosis of),ERA<3 months),imaging diagnosis of synovitis without autoantibody and high inflammatory level,and poor prognosis.And morning stiffness time,CRP,HAQ and other indicators affecting the activity of the disease.The indexes that did not affect the baseline disease activity were as follows:sex,way of entering the group.The curative effect of F group:the indexes of morning stiffness,HAQ,SDAI,CDAI,DAS28-ESR and other indexes of activity,function and inflammation in group F were significantly lower than those in the baseline after 6 months of completion(p<0.05),and the indexes of activity,function and inflammation in group F were significantly lower than those in the baseline(p<0.05).After 6 months of treatment,the clinical remission rate of DAS28-ESR was 52%,the clinical remission rate of SDAI was 49%,the clinical remission rate of CDAI was 74%,the good response rate of ? DAS28-ESR was 46%,the remission rate of ACR20 was 76%,and the remission rate of EULAR was 30%.According to the different indexes of the baseline,it was found that there was no significant difference in the description and statistics of each subgroup at the baseline,and the activity index of each disease was significantly lower than that of the baseline at the three time points of January,March and June(p<0.05).At 6 m time point,remission or low disease activity can be achieved to varying degrees.The curative effect of uf group was significantly lower than that of f group,and the baseline crp of uf group was significantly higher than that of f group.Comparison of adverse reactions between group UF and group F:there were 37 adverse reactions in group F during 6 months of treatment,including abnormal liver function,infection,digestive tract symptoms,abnormal skin and mucous membrane,abnormal renal function and cardiovascular events.Peripheral neuropathy.Adverse reactions occurred 7 times in UF group.In all the population,there were mainly:ERA or UA,negative antibody,poor prognosis,less nave group,short course of course and mild baseline condition.The summary of the baseline and the whole treatment plan found that the two-linked,triple and tralogy of performance were the highest,and it was worthy of clinical promotion.ConclusionIn this experiment,IGU as the center of the drug regimen in the treatment of ERA,achieved good results,especially for the morning stiffness time,high CRP,prognosis factors,long course of elderly ERA patients have a better effect.It shows that IGU is the main treatment,the combination of double to quadruple therapy has high performance-price ratio and less adverse reactions,which is worthy of clinical promotion.