The Medical Treatment In Moderate To Severe Ulcerative Colitis And Analysis Of Related Factors Of The Efficacy

BackgroundUlcerative colitis(UC)is a chronic,idiopathic inflammatory disease that affects the colon and rectum,and its incidence is rising worldwide,especially in the new industrialized countries.UC is characterised by relapsing and remitting mucosal inflammation,and the main clinical features include diarrhoea,rectal bleeding,abdominal pain,tenesmus and different degrees of systemic symptoms.It seriously affects the lives and work of patients,and resulting in disability.The etiology and pathogenesis of UC is not yet very clear.Traditional treatments for UC include 5-aminosalicylic acid drugs,glucocorticoids(GCS),and immunosuppressants.Patients with moderate to severe colitis,especially acute severe ulcerative colitis(ASUC),have a severe condition and poor prognosis,and some of them have poor response to traditional drugs.Studies have shown that a new biological agent,infliximab(IFX),which is a type of anti-TNF-a drugs,could induce and maintain remission in moderate to severe disease effectively.And it can also be used as a salvage therapy in patients with ASUC and refractory to steroid.At present,global multicenter studies have confirmed the efficacy and safety of IFX in moderate to severe colitis.However,There are only a few studies with small sample size based on Chinese population.In the first part of the study,we retrospectively analyzed the efficacy of intravenous GCS and salvage therapy in ASUC,and identified the related factors of GCS efficacy.In the second part,we further explored the efficacy,safety of IFX in Chinese patients with moderate to severe UC,and identified the related factors of the efficacy.In the third part,we performed a systematic review and meta-analysis to evaluate the efficacy and safety of IFX dose intensification in moderate to severe UC with secondary loss of response to IFX.Chapter 1 The efficacy of glucocorticoids in acute severe ulcerative colitis and analysis of related factorsObjectiveTo evaluate the efficacy of intravenous GCS in ASUC,and identify the related factors of the efficacy.MethodsFrom January 2006 to October 2017,we retrospectively reviewed the clinical,laboratory,endoscopy data of 43 patients with ASUC who received intravenous GCS treatment at Nanfang Hospital.We evaluated the efficacy of GCS and followed the patients up to analyze the outcomes.Univariate and multivariate Logistic regression were performed to analyze the related factors of response to GCS.ResultsA total of 43 ASUC patients were included,male to female ratio was 1.26:1,the mean age of on set was 38.2 years.Among the patiens,58.1%(25/43)had a age of on set less than 40 years,88.4%(38/43)were chronic relapse type,and 62.8%(27/43)had pancolitis.All of the patients underwent intravenous GCS treatment,the effective rate was 62.8%(27/43).9 patients received medicine rescue therapy.8 cases were treated with IFX,of which 6 cases induced remission,1 case happened to secondary loss of response,and 1 case was ineffective.Another 1 case was treated with cyclosporin A,which was ineffective and then changed to IFX+AZA therapy effectively.The effective rate of medicine rescue therapy was 88.8%(8/9).The colectomy rate was 11.6%(5/43)with 30 days,and the other patients did not have intestinal resection within 1 year of follow-up.Univariate analysis showed that severe attack history,previous GCS therapy,deep ulcer,a stool frequency>6 and obvious bloody stools on the third day of treatment were related to poor GCS efficacy(all P<0.05).Multivariate logistic regression analysis showed that severe attack history(OR=7.244,95%CI:1.156-45.405,P=0.034)and obvious bloody stools on the third day of treatment(OR=6.305,95%CI:1.036-38.387,P=0.046)were independent risk factors of poor GCS efficacy.ConclusionMost of ASUC were chronic relapse type and pancolitis.The effective rate of GCS was 62.8%.Severe attack history,previous GCS therapy,deep ulcer,a stool frequency>6 and obvious bloody stools on the third day of treatment were related to GCS efficacy.Severe attack history and obvious bloody stools on the third day of treatment were independent risk factors of poor GCS efficacy.Chapter 2 The efficacy and safety of infliximab in moderate to severe ulcerative colitis and analysis of related factorsObjectiveTo evaluate the clinical efficacy and safety of infliximab in Chinese patients with moderate to severe UC,and identify the related factors of the efficacy.MethodsFrom January 2011 to October 2017,we retrospectively reviewed the clinical data of 58 patients with moderate to severe UC who received IFX treatment at Nanfang Hospital.The short-and long-term outcomes were assessed at week 14 and week 30,and adverse events were evaluated,and predictors of response and remission were identified.Furthermore,we compared the efficacy of IFX with IFX combined azathioprine(AZA).ResultsA total of 58 UC patients were included,the mean age of on set was 38.7 years,and the median of the follow-up was 11.5 months(range:1-51 months).The mean Mayo score of baseline was 9.97±1.57.At week 14,the rates of clinical response and remission were 82.1%(46/56)and 32.1%(18/56);At week 30,the rates of clinical response and remission were 70.2%(33/47)and 46.8%(22/47).A total of 52.9%(27/51)of the patients achieved mucosal healing and 6.9%(4/58)of the patients underwent colectomy during follow-up period.At week 14,rates of clinical response of IFX group and IFX+AZA group were 77.6%(38/49)vs 88.9%(8/9)(P>0.05);rates of clinical remission of IFX group and IFX+AZA group were 24.5%(12/49)vs 66.7%(6/9)(P<0.05).And we found that the combination therapy with AZA was the only significant predictor of clinical remission at week 14.Adverse events occurred in 22.4%(13/58)of patients,with most being mild,but 3 patients(5.2%)occurred active tuberculosis(TB).ConclusionIFX could induce and maintain clinical remission in Chinese patients with moderate to severe UC effectively.And patients treated with IFX+AZA were more likely to achieve clinical remission at week 14 than those receiving IFX monotherapy.IFX was relatively safe in Chinese paitients,but the incidence of TB in our study is higher than previously reported.Considering the high incidence of TB in China,it is necessary to strengthen the screening of latent tuberculosis infection and preventive anti-TB treatment before IFX therapy.Chapter 3 Systematic review with meta-analysis:the efficacy and safety of dose optimization in ulcerative colitis patients with secondary loss of response to infliximabObjectiveTo perform a systematic review and meta-analysis to evaluate the efficacy and safety of infliximab dose intensification in ulcerative colitis patients who lost response to infliximab.MethodsA systematic literature search was performed in English databases,including PubMed/Medline and Ovid,and Chinese databases,including Chinese periodical full-text database(CNKI),Wanfang resource database and Chinese technological periodical full-text database(VIP).Relevant published artcles were searched until December 2017.Studies reporting the efficacy and safety of infliximab dose optimization(Dose doubling or Interval shortening)in ulcerative colitis patients were included.The outcomes were the pooled rates of rapid and sustained clinical response or remission,rates of colectomy,adverse events.The pooled rates were performed by a random or fixed effects model.The MINORS was used to assess the quality of evidence.ResultsOf the collective 5,920 initial candidate articles,5 retrospective studies with 321 patients in 28 medical centers were ultimately included in the analysis.The pooled rate of rapid clinical response was 71%(I2=93.9%,random effects model,95%CI:50%-92%,n=277).The pooled rate of rapid clinical remission was 52%(I2=98%,random effects model,95%CI:17%-88%,n=294).Sustained clinical response or remission rate at 52 week was 49%(I2=92.6%,random effects model,95%CI:21%-77%,n=147).The pooled colectomy rate during follow-up was 18%(I2=74.8%,random effects model,95%CI:9%-27%,n=304).The pooled adverse events rate during follow-up was 8%(I2=0.0%,fixed effects model,95%CI:5%-12%,n=277).No one died during the follow up period of dose optimization.ConclusionDose optimization(Dose doubling or Interval shortening)was effective and safe for part of ulcerative colitis patients who lost response to infliximab.Prospective studies with large sample size are still needed to text its efficacy and safety.