Ulcerative colitis patients in clinical remission demonstrate correlations between fecal immunochemical test results, mucosal healing, and risk of relapse

AIM: To assess the risk of relapse in ulcerative colitis (UC) patients in clinical remission using mucosal status and fecal immunochemical test (FIT) results.METHODS: The clinical outcomes of 194 UC patients in clinical remission who underwent colonoscopy were based on evaluations of Mayo endoscopic subscores (MESs) and FIT results.RESULTS: Patients with an MES of 0 (n = 94, 48%) showed a ten-fold lower risk of relapse than those with an MES of 1-3 (n = 100, 52%) (HR = 0.10, 95%CI: 0.05-0.19). A negative FIT result (fecal hemoglobin concentrations ≤ 100 ng/mL) was predictive of patients with an MES of 0, with a sensitivity of 0.94 and a specific of 0.76. Moreover, patients with a negative FIT score had a six-fold lower risk of clinical relapse than those with a positive score (HR = 0.17, 95%CI: 0.10-0.28). Inclusion of the distinguishing parameter, sustaining clinical remission > 12 mo, resulted in an even stronger correlation between negative FIT results and an MES of 0 with respect to the risk of clinical relapse (HR = 0.11, 95%CI: 0.04-0.23).CONCLUSION: Negative FIT results one year or more after remission induction correlate with complete mucosal healing (MES 0) and better prognosis. Performing FIT one year after remission induction may be useful for evaluating relapse risk.

Probiotic Medilac-S^(█) for the induction of clinical remission in a Chinese population with ulcerative colitis: A systematic review and meta-analysis

AIM To assess the effects of probiotic Medilac-S~ as adjunctive therapy for the induction of remission of ulcerative colitis(UC) in a Chinese population through a systematic review and meta-analysis. METHODS A systematic literature search was conducted to find randomized, controlled trials in a Chinese population with at least two study arms-a control arm which receives a conventional, oral aminosalicylate drug, and a treatment arm, which administers the same conventional drug in conjunction with the probiotic Medilac-S~ per os. Both English and Chinese databases were searched, including Pub Med, EMBASE, Google Scholar, Chinese National Knowledge Infrastructure, Wanfang Data, and VIP Search, and study data was extracted onto standardized abstraction sheets. Meta-analyses were conducted for primary and secondary outcomes of interest using a fixed or random effects model. The primary outcome was the induction of clinical remission and the secondary outcomes included changes in Sutherland index, endoscopic and histological scores, proportion of reported clinical symptoms and adverse events(AEs). For outcomes with sufficient data, the type of conventional drug therapy was also assessed to determine if the effects of combination therapy with Medilac-S~ was influenced by drug type. All tests were conducted using a type Ⅰ error rate of 0.05 and all confidence intervals(CI) were based on a 95% confidence level. Review protocol was uploaded to PROSPERO(CRD42018085658 upon completion).RESULTS Fifty-three clinical trials with a total of 3984 participants were identified and included in the review. Medilac-S~ adjunctive therapy significantly improved induction of clinical remission(RR = 1.21; 95%CI: 1.18-1.24; P < 0.0001) with the estimated likelihood of effective treatment, on average, 21% higher for those consuming the probiotic. Sutherland index scores showed the control mean was on average 3.10(CI: 2.41-3.78; P = 0.0428) units greater than the treatment mean, thereby demonstrating significant improvement in participants taking the probiotic. Similarly, a significant difference was seen between the overall reduction of endoscopic and histological scores of control and treatment arm participants, with score decreases in the control groups 0.71(CI: 0.3537-1.0742) and 1.1(CI: 0.9189-1.2300) units smaller than treatment group score decreases. The proportion of participants reporting clinical symptoms,(abdominal pain, tenesmus, blood and mucous in stool, and diarrhea) was significantly reduced after combination therapy with Medilac-S~(P < 0.0001) and estimated to be on average 44%(RR = 0.44, CI: 0.32-0.59), 53%(RR = 0.53, CI: 0.38-74), 40%(RR = 0.40, CI: 0.28-0.58) and 47%(RR = 0.47 CI: 0.36-0.42) respectively, of the proportion of individuals reporting the aforementioned symptoms after conventional therapy alone. The risk of AEs was also significantly reduced with adjunctive Medilac-S~ therapy. The proportion of individuals in the treatment groups reporting AEs was an estimated 72% of the proportion of individuals in the control groups reporting AEs(RR = 0.72, CI: 0.55-0.94, P = 0.0175). Upon comparing effect means for different drug types in conjunction with Medilac-S~, evidence of significant variability(P < 0.0001) was observed, and sulfasalazine was found to be the most effective drug in both primary and secondary outcomes. CONCLUSION Evidence suggests Medilac-S~ adjunctive therapy should be considered standard care for UC in a Chinese population because it aids in the induction of clinical remission, improves symptoms of the gastrointestinal tract and reduces risk of AEs.

Long-term sustained clinical remission of peritoneal metastatic pancreatic ductal adenocarcinoma after sequential chemoradiation therapy: a case report

Patients with peritoneal metastatic pancreatic ductal adenocarcinoma(pmPDAC)with high-level serum carbohydrate antigens(CAs)always suffer extremely dismal prognosis,with a median survival of several months.Herein,we reported a case of pmPDAC with high serum CAs who had long-term clinical remission with normalization of CAs after chemoradiation.In November 2019,a 64-year-old male patient was admitted to our center with a solid mass measuring 2.8×2.5×2.0 cm in the body of the pancreas near the celiac trunk.Positron emission tomography-computed tomography(PET-CT)revealed an standardized uptake value max(SUVmax)of 4.2.The serum CA 242 level exceeded 150.0 U/mL(normal range:0–20 U/mL),and CA 19-9 was elevated at 975.2 U/mL(normal range:0–34 U/mL).During laparotomy,the tumor was found to encircle the celiac trunk over 180°,with several small peritoneal nodules in the lesser omental cavity.Pathological examination confirmed the diagnosis of pmPDAC.Nextgeneration sequencing revealed RAS G12V,EGFR mutation(-),low tumor mutation burden(TMB),and microsatellite stability(MSS).The patient underwent 6 cycles of the AG regimen(gemcitabine plus nab-paclitaxel),resulting in significant tumor shrinkage and a sharp decline in CAs.Partial remission was achieved.However,due to intolerant neurotoxicity,the AG regimen was discontinued.Subsequently,synchronous oral fluorouracil(S1)and radiation therapy were administered.Five months after radiation treatment,all CAs normalized.Oral S1 was continued for an additional 3 months.Eventually,all anti-cancer drugs were stopped.Computed tomography scans indicated that the tumor still surrounded the celiac trunk and common hepatic artery.After a thorough discussion,a wait-and-see strategy was adopted.Remarkably,32 months after stopping anti-cancer medication,the patient remains in good health,with sustained normalization of CAs.At the last follow-up,he had lived for 50 months,and the normalization of the CAs was sustained for 36 months.Although he still suffers the risk of disease progression,it is a successful case of state-of-the-art chemoradiation for a dismal pmPDAC patient.

Disease clearance in ulcerative colitis:A new therapeutic target for the future

Advancements in murine modeling systems for ulcerative colitis have diversified our understanding of the pathophysiological factors involved in disease onset and progression.This has fueled the identification of molecular targets,resulting in a rapidly expanding therapeutic armamentarium.Subsequently,management strategies have evolved from symptomatic resolution to well-defined objective endpoints,including clinical remission,endoscopic remission and mucosal healing.While the incorporation of these assessment modalities has permitted targeted intervention in the context of a natural disease history and the prevention of complications,studies have consistently depicted discrepancies associated with ascertaining disease status through clinical and endoscopic measures.Current recommendations lack consideration of histological healing.The simultaneous achievement of clinical,endoscopic,and histologic remission has not been fully investigated.This has laid the groundwork for a novel therapeutic outcome termed disease clearance(DC).This article summarizes the concept of DC and its current evidence.

Role of the combination of biologics and/or small molecules in the treatment of patients with inflammatory bowel disease

Inflammatory bowel disease(IBD)is a group of chronic diseases that includes ulcerative colitis,Crohn’s disease,and indeterminate colitis.Patients with IBD require prolonged treatment and high utilization of healthcare resources for proper management.The treatment of patients with IBD is focused on achieving therapeutic goals including clinical,biochemical,and endoscopic variables that result in improvement of the quality of life and prevention of disability.Advanced IBD treatment includes tumor necrosis factor inhibitors,integrin antagonist,antagonist of the p40 subunit of interleukin 12/23,and small molecule drugs.However,despite the multiple treatments available,about 40%of patients are refractory to therapy and present with persistent symptoms that have a great impact on their quality of life,with hospitalization and surgery being necessary in many cases.Dual therapy,a strategy sometimes applicable to refractory IBD patients,includes the combination of two biologics or a biologic in combination with a small molecule drug.There are two distinct scenarios in IBD patients in which this approach can be used:(1)Refractory active luminal disease without extraintestinal manifestations;and(2)patients with IBD in remission,but with active extraintestinal manifestations or immune-mediated inflammatory diseases.This review provides a summary of the results(clinical response and remission)of different combinations of advanced drugs in patients with IBD,both in adults and in the pediatric population.In addition,the safety profile of different combinations of dual therapy is analyzed.The use of newer combinations,including recently approved treatments,the application of new biomarkers and artificial intelligence,and clinical trials to establish effectiveness during long-term followup,are needed to establish new strategies for the use of advanced treatments in patients with refractory IBD.

Infliximab trough level combined with inflammatory biomarkers predict long-term endoscopic outcomes in Crohn’s disease under infliximab therapy

BACKGROUND Infliximab trough level(ITL)severely affects therapeutic outcomes of Crohn’s disease(CD)patients under infliximab(IFX).Recently,frontier research has focused on identifying ITL based on different therapeutic targets.Although previous studies have elaborated clinical value of ITL monitoring on short-term outcomes in CD patients during therapy,studies contraposing the predictive value of ITL on long-term endoscopic outcomes in CD patients are still scarce domestically and overseas.AIM To explore the predictive value of ITL in combination with inflammatory biomarkers on long-term endoscopic outcomes in CD with clinical remission during IFX maintenance therapy.METHODS CD patients with endoscopic remission under long-term IFX maintenance therapy in the First Affiliated Hospital of Zhejiang Chinese Medicine University from January 2012 to December 2020 were collected.ITL and inflammatory biomarkers were continuously monitored during the therapy.The Step I study was conducted from weeks 14 to 54 of IFX treatment.The Step II study was conducted from weeks 54 to 108 of IFX treatment.Endoscopic outcomes were defined as endoscopic activity(Crohn’s disease endoscopic index of severity score>2 points or Rutgeerts score>i1)and endoscopic remission(Crohn’s disease endoscopic index of severity score≤2 points or Rutgeerts≤i1).Endoscopic relapse free survival was defined as endoscopic remission at the beginning of the study stage and maintaining endoscopic remission during the study stage.RESULTS At week 14,low ITL[odds ratio(OR)=0.666,95%confidence interval(CI):0.514-0.862,P<0.01]and high fecal calprotectin(FCP)level(OR=1.002,95%CI:1.001-1.004,P<0.01)increased the risk of endoscopic activity at week 54.At week 54,low ITL(OR=0.466,95%CI:0.247-0.877,P<0.01)and high C-reactive protein(CRP)level(OR=1.590,95%CI:1.007-2.510,P<0.01)increased the risk of endoscopic activity at week 108.At week 14,ITL≤5.60μg/mL[area under the curve(AUC)=0.83,95%CI:0.73-0.90,P<0.001]and FCP>238μg/g(AUC=0.82,95%CI:0.72-0.89,P<0.001)moderately predicted endoscopic activity at week 54.ITL≤5.60μg/mL in combination with FCP>238μg/g indicated 82.0%possibility of endoscopic activity.At week 54,ITL≤2.10μg/mL(AUC=0.85,95%CI:0.72-0.93,P<0.001)and CRP>3.00 mg/L(AUC=0.73,95%CI:0.60-0.84,P=0.012)moderately predicted moderate endoscopic activity at week 108.ITL≤2.10μg/mL in combination with CRP>3.00 mg/L indicated 100.0%possibility of endoscopic activity.From weeks 14 to 54 of IFX treatment,patients with ITL>5.60μg/mL had higher rate of endoscopic relapse free survival than those with ITL≤5.60μg/mL(95.83%vs 46.67%).From weeks 54 to 108 of IFX treatment,patients with ITL>2.10μg/mL had higher rate of endoscopic survival free relapsed rate than those with ITL≤2.10μg/mL(92.68%vs 30.77%).CONCLUSION Combination of ITL,CRP,and FCP contribute to long-term endoscopic prognosis monitoring.During IFX maintenance treatment,low ITL,high CRP level,and high FCP level were independent risk factors of CD patients with clinical remission in adverse endoscopy outcomes within 1-year follow-up.

The efficacy and safety of thalidomide in the treatment of refractory Crohn’s disease in adults:a double-center,double-blind,randomized–controlled trial

Background Thalidomide is applied in therapy for refractory Crohn’s disease(CD)in adults,but systematic and rigorous clinical evidence is scant.The aim was to provide theoretical references for the efficacy of thalidomide in the therapy for refractory CD in adults.Methods A double-center,double-blind,placebo-controlled,randomized clinical trial of refractory CD in adults in two inflammatory bowel disease centers in China.In the double-blind trial,patients were randomly assigned to 100mg of thalidomide or placebo daily for 8 weeks.The primary outcome was considered as the clinical remission rate calculated based on the Crohn’s disease activity index at the eighth week following thalidomide or placebo treatment.In open label,nonresponse to placebo was additionally treated with 8 weeks of thalidomide;all responders were continuously treated with thalidomide until the 48th week.Results Twenty-five patients were randomly assigned to each group.At the eighth week,the clinical remission rate in the thalidomide group was significantly higher than that in the placebo group(68.0%[17/25]vs 16.0%[4/25];relative risk,4.2;95%confidence interval,1.8–10.9,P<0.001).After a 48-week follow-up,the continuous treatment rate of thalidomide was 46.3%(19/41).Adverse events during the whole process were reported in 58.5%of patients,mainly involving drowsiness,rash,and peripheral neuropathy that were mild and tolerable.Conclusion Thalidomide can be used in the induction and maintenance therapy of refractory CD in adults.And it could be one of the treatment options for refractory CD.