Predictors And Clinical Outcome Of Infliximab-withdrawal Crohn’s Disease Patients In The Medium-term Follow-up

Crohn’s Disease(CD)is a chronic and nonspecific gastrointestinal inflammation with complex and diverse extra digestive manifestations.The cause of the disease is not clear yet,but it is believed closely related to genetic susceptibility,environmental factors,intestinal microbial changes,abnormal immune response and so on[1].Currently,the treatment strategy is to continuously achieve the established treatment objectives,namely,the "standard treatment" strategy[2],maintain remission treatment,to prevent complications,intestinal failure and CD-related surgeries,and improve the quality of life of patients.With the development of immunology and people’s understanding of diseases,the strategies of early treatment,combination therapy of immunosuppressive agents and biological agents[3] are gradually applied in clinical practice and have been proved good curative effect.However,for patients in remission stage,it is still debatable whether biological agents should be used continuously and how to classify patients according to their risk factors,in order to adopt different strategies for drug use during remission.In 2012,STORI,a prospective study of CD patients in Europe and America,was followed up for more than two years after patients reached remission.It was found that about 50% of patients who discontinued biological agents did not experience recurrence during the 28-month followup period,suggesting that some low-risk patients could discontinue biological agents after remission[4].In recent years,a series of retrospective studies have been carried out in Europe on drug withdrawal strategies,but no consensus has been reached.SPARE,a three-arm clinical trialwhich is still recruiting patients,is expected to provide further prospective evidence to support correct drug withdrawal strategies.On the other hand,in China,the research in this area is almost blank.In view of the increasing incidence of CD in developing countries in recent years[5],and the clinical characteristics and prognosis of CD patients in eastern and Western countries are significantly different,it is worthy to discuss the discontinuation strategy of CD patients in China.Section Ⅰ[Background and goals] It is important to determine whether Infliximab(IFX)could be safely discontinued in patients with Crohn’s Disease(CD)after ensure therapy was effective.We assessed the risk of clinical relapse after IFX withdrawn in effective Chinese CD patients and identified factors associated with clinical relapse.[Methods] From 322 CD patients,97 patients included in this study.IFX then was been discontinued and patients were followed up for at least one year.We divided patients into different sub-group according their medication and therapy target,evaluated demographic,clinical and biologic factors with time to relapse using a Cox model to identify risk factor of clinical relapse separately.[Results] After a median follow-up period of 31 months,48 of the 97 patients experienced a clinical relapse;the 1-year relapse rate was 23.7%.The median time from IFX cessation to clinical relapse was 40.0 months.The 1-year relapse rate of musical healing subgroup and partial mucosal healing group was 15.7% and 32.6% separately.Patients taking thiopurine after the withdrawal had the low 1-year relapse rate(6.2%)while contrast to the other drug taking.Retreatment of IFX to relapsing patients still effective.[Conclusions] Approximately 25% of Chinese CD patients experienced a clinical relapse during the first year after IFX discontinuation.Patients should reach mucosal and take thiopurine after withdrawal to lower the relapse rate.IFX restart still effective after relapse,which indicate patients can be classified according their risk factors and take different exit strategy.Section ⅡInflammatory bowel disease(IBD)is a chronic,progressive and non-specific intestinal inflammation,which includes Crohn’s disease(CD)and Ulcerative Colitis(UC).Its chronic recurrent course seriously affects patient’s quality of life(Qo L).Conventional medicines include aminosalicylic acid,immunosuppressive agents and glucocorticoids.However,due to its adverse reactions and especially,poor efficacy to severe patients,patients were not so compliant.Since the first anti-Tumor Necrosis Factor alpha(TNFα)monoclonal antibody—Infliximab(IFX),came into market,the clinical remission rate of IBD has been greatly improved.IFX has also been widely used in clinic,while the problem also arises: about one third of patients would have no response to the initial use,and about 20% per year of patients would fail to respond to IFX in the later usage.Therefore,development of new drugs targeting to other inflammatory factors or inflammation-related signal pathways are crucial.Although the pathogenesis of IBD is still unknown,many abnormal downstream cytokines have been detected and proved to be closely related to the severity of the disease.In addition to abnormal elevation of TNFα,elevated expression of interleukin(IL)-12,IL-23 and leukocyte adhesion factor were also been detected in active disease.Blocking the above cytokines can effectively prevent the inflammatory reaction downstream and intestinal mucosal damage caused by leukocyte chemotaxis.Drugs targeting these target factors can effectively control symptoms and delay the course of disease.Therefore,this article would like to summary the research progresses of new biological agents in IBD treatment in recent years.