Relapse Of Colitis Research Articles

A characterization of pro-inflammatory cytokines in dextran sulfate sodium-induced chronic relapsing colitis mice model

Repeated cycles of dextran sulfate sodium (DSS) administration in mice, inducing chronic relapsing colitis, have been used to mimic human ulcerative colitis (UC). However, no systematic characterization of pro-inflammatory cytokines in these DSS mice has been reported. In this study, the development of colitis was examined by assessment of the disease severity and inflammation in the colon of C57BL/6 mice that received DSS. ELISA was used to analyze the levels of pro-inflammatory cytokines in serum, colon, spleen and supernatant of cultured splenocytes. mRNA levels of the above cytokines in colon and mesenteric lymph node (MLN) were measured with RT-PCR. The mice receiving three cycles of 2% DSS over a 43-day period showed a fluctuating appearance of diarrhea and bloody feces, and a significant reduction in body weight and colon length. When compared with normal control mice, an increase in TNF-α level in serum was detected in the DSS mice, along with a decrease in the amounts of TNF-α, IL-17, IL-1β and IL-6 in the colonic tissue. However, mRNA levels of these cytokines were found to be significantly increased in the colon while decreased in the MLN of the colitis mice. Further, the ELISA assay suggested a pronounced increase of TNF-α production by cultured splenocytes with PMA/ionomycin re-stimulation but no increase in its presence in spleen tissue upon DSS challenge. In conclusion, we have systematically demonstrated the dysregulation of pro-inflammatory cytokines in the DSS-induced chronic relapsing colitis model, which will provide markers to test emerging therapeutic strategies by this model.

Role of TNFα Antagonists in Susceptibility to Mycobacterial Infection in Association with Genetic Polymorphisms in Crohn’s Disease

Abstract Crohn’s disease (CD) is a relapsing inflammatory bowel disease that has been associated with bacterial triggers such as Mycobacterium avium subspecies paratuberculosis (MAP). Overreactive immune response in CD patients involves a significant elevation in Tumor Necrosis Factor alpha (TNFα), which causes upregulation in multiple cytokine levels, leading to formation and maintenance of granuloma. Standard CD treatment includes immunomodulators and biologics such as Anti-TNFα. We hypothesize that blocking TNFα promotes MAP survival which worsens the disease condition. Therefore, CD treatment plan should include MAP-specific antibiotics and novel cytokine targets based on personalized medicinal approach. RHB-104, a triple antibiotics formulation ((63.3 %) clarithromycin, (6.7 %) clofazimine, and (30 %) rifabutin), recombinant TNFα, adalimumab (Humira®), and certolizumab pegol (Cimzia®) were evaluated in vitro for effect on MAP culture and macrophages infected with MAP. As expected, RHB-104 was detrmintal to MAP (MIC< 2ug/mL), while anti-TNFα therapeutics had no direct bactericidal effects at concentrations as high as 4x Cmax. Recombinant TNFα reduced MAP survival in infected macrophages by 2.63 logs. On the contrary, both anti-TNFα therapeutics promoted MAP survival by 1.54 logs. Additionally, we have identified 2 significant single nucleotide polymorphisms (rs767455 and rs3397) related to TNFR superfamily 1(A/B) in 54 CD patients compared to 50 healthy subjects by using TaqManTM genotyping assay. This study should provide i) data about the safety of Anti-TNFα biologics in CD patients-associated with MAP infection and ii) predictions toward response to treatment plan based on patient’s pharmacogenomics.

Microscopic colitis in patients with ulcerative colitis or Crohn’s disease: a retrospective observational study and review of the literature

Objectives: Onset of microscopic colitis (MC) in patients with ulcerative colitis (UC) or Crohn’s disease (CD), or vice versa, has been reported occasionally but the subject is not well described. We therefore report a retrospective observational study of such patients and review the literature.Methods: Forty-six Swedish gastroenterology clinics were contacted about patients with diagnoses of both inflammatory bowel disease (IBD) and MC. Publications were searched on PubMed.Results: We identified 31 patients with onset of MC after a median (range) of 20 (2–52) years after diagnosis of IBD, or vice versa; 21 UC patients developed collagenous colitis (CC) (n = 16) or lymphocytic colitis (LC) (n = 5); nine CD patients developed CC (n = 5) or LC (n = 4); one CC patient developed CD. Of the 21 UC patients, 18 had extensive disease, whereas no consistent phenotype occurred in CD. Literature review revealed 27 comprehensive case reports of patients with diagnoses of both IBD and MC. Thirteen MC patients developed IBD, of which four required colectomy. Fourteen IBD patients later developed MC. There were incomplete clinical data in 115 additional reported patients.Conclusions: Altogether 173 patients with occurrence of both IBD and MC were found. The most common finding in our patients was onset of CC in a patient with UC. Although these are likely random associations of two different disorders, MC should be considered in the patient with UC or CD if there is onset of chronic watery diarrhoea without endoscopic relapse of IBD.

Low dose Naltrexone for induction of remission in inflammatory bowel disease patients

BackgroundAround 30% of patients with inflammatory bowel disease (IBD) are refractory to current IBD drugs or relapse over time. Novel treatments are called for, and low dose Naltrexone (LDN) may provide a safe, easily accessible alternative treatment option for these patients. We investigated the potential of LDN to induce clinical response in therapy refractory IBD patients, and investigated its direct effects on epithelial barrier function.MethodsPatients not in remission and not responding to conventional therapy were offered to initiate LDN as a concomitant treatment. In total 47 IBD patients prescribed LDN were followed prospectively for 12 weeks. Where available, endoscopic remission data, serum and biopsies were collected. Further the effect of Naltrexone on wound healing (scratch assay), cytokine production and endoplasmic reticulum (ER) stress (GRP78 and CHOP western blot analysis, immunohistochemistry) were investigated in HCT116 and CACO2 intestinal epithelial cells, human IBD intestinal organoids and patient samples.ResultsLow dose Naltrexone induced clinical improvement in 74.5%, and remission in 25.5% of patients. Naltrexone improved wound healing and reduced ER stress induced by Tunicamycin, lipopolysaccharide or bacteria in epithelial barriers. Inflamed mucosa from IBD patients showed high ER stress levels, which was reduced in patients treated with LDN. Cytokine levels in neither epithelial cells nor serum from IBD patients were affected.ConclusionsNaltrexone directly improves epithelial barrier function by improving wound healing and reducing mucosal ER stress levels. Low dose Naltrexone treatment is effective and safe, and could be considered for the treatment of therapy refractory IBD patients.

Accuracy of Consecutive Fecal Calprotectin Measurements to Predict Relapse in Inflammatory Bowel Disease Patients Under Maintenance With Anti-TNF Therapy: A Prospective Longitudinal Cohort Study.

Predicting relapse in inflammatory bowel disease (IBD) patients could allow early changes in therapy. We aimed at evaluating the accuracy of consecutive fecal calprotectin (FC) measurements to predict flares in IBD patients under maintenance treatment with anti-tumor necrosis factor (TNF) drugs. A prospective longitudinal cohort study with 16-month follow-up period was designed. IBD patients in clinical remission for at least 6 months under anti-TNF therapy were included. FC was quantified at 4-month intervals for 1 year, and patients were clinically evaluated for relapse at 2-month intervals. Diagnostic accuracy of FC for predicting relapse was evaluated by receiver-operating characteristic curve analysis. In total, 95 of 106 included patients finalized the study and were analyzed (median age 44 y, 50.5% female, 75% with Crohn's disease). A total of 30 patients (31.6%) had a relapse over follow-up. FC concentration was significantly higher in patients who relapsed (477 μg/g) than in patients who maintained in remission (65 μg/g) (P<0.005). The optimal cutoff to predict remission was 130 μg/g (negative predictive value of 100%), and 300 μg/g to predict relapse (positive predictive value of 78.3%). FC is a good predictor of clinical relapse and a particularly good predictor of remission over the following 4 months in patients with IBD on maintenance therapy with anti-TNF drugs. FC levels <130 μg/g is consistently associated with maintained disease remission, whereas concentrations >300 μg/g allow predicting relapse with a high probability at any time over the following 4 months.

Non-alcoholic fatty liver disease phenotypes in patients with inflammatory bowel disease

Non-alcoholic fatty liver disease (NAFLD) can be detected in up to 33.6% of inflammatory bowel disease (IBD) patients, often in absence of metabolic risk factors. Nevertheless, most of previous studies on such issue were conducted within the IBD population only. The primary aim of this study was to compare clinical and metabolic features of NAFLD in patients with and without IBD (w/o IBD) and to identify specific NAFLD phenotypes within the IBD population. Among 223 NAFLD patients, 78 patients with IBD were younger compared to 145 without (w/o) IBD, were less likely to have altered liver enzymes, had lower mean body weight, smaller waist circumference and lower body mass index (BMI); at the same time, MetS was more prevalent among patients w/o IBD (56.6 vs. 23.1%, p < 0.001). Within IBD population, patients with severe IBD showed more often severe steatosis (S3) at ultrasound (US) (32.1 vs. 16.6%, p = 0.01), compared to mild-to-moderate disease. Independent risk factors for S3 US steatosis in IBD patients at the multivariate logistic regression analysis were: more than 1 IBD relapse per year during disease history (OR 17.3, 95% CI 3.6–84), surgery for IBD (OR 15.1, 95% CI 3.1–73.7) and more extensive intestinal involvement (OR 19.4, 95% CI 3.4–110.9); the ongoing anti-Tumor Necrosis Factor alpha (antiTNFα) therapy was the only independent factor which protect toward the presence of altered liver enzymes (OR 0.15, 95% CI 0–0.8, p = 0.02). In conclusion, NAFLD in IBD patients is different from that in patients w/o IBD, who seem to develop different NAFLD phenotypes according to intestinal disease clinical course. More severe IBD seem to predict the presence of more severe steatosis. Therapy with antiTNFα antibodies could prevent alteration of liver enzymes in such population.

The Value of Fecal Markers in Predicting Relapse in Inflammatory Bowel Diseases

The inflammatory bowel diseases (IBDs) are lifelong chronic illnesses that place an immense burden on patients. The primary aim of therapy is to reduce disease burden and prevent relapse. However, the occurrence of relapses is often unpredictable. Current disease monitoring is primarily by way of clinical indices, with relapses often only recognized once the inflammatory episode is established with subsequent symptoms and gut damage. The window between initial upregulation of the inflammatory response and the recognition of symptoms may provide an opportunity to prevent the relapse and associated morbidity. This review will describe the existing literature surrounding predictive indicators of relapse of IBD with a specific focus on fecal biomarkers. Fecal biomarkers offer promise as a convenient, non-invasive, low cost option for disease monitoring that is predictive of subsequent relapse. To exploit the potential of fecal biomarkers in this role, further research is now required. This research needs to assess multiple fecal markers in context with demographics, disease phenotype, genetics, and intestinal microbiome composition, to build disease behavior models that can provide the clinician with sufficient confidence to intervene and change the long-term disease course.

P384 Gari-leo prospective study on anti-TNF therapy in ulcerative colitis relapse patients

P384 Gari-leo prospective study on anti-TNF therapy in ulcerative colitis relapse patients

P181 ENTERIC INFECTION IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE: ENDOSCOPIC AND HISTOLOGIC FINDINGS DO NOT DIFFERENTIATE INFECTION FROM FLARE

The similar presentations in relapse of inflammatory bowel disease (IBD) and enteric infection pose substantial barriers to diagnosis and treatment. The objective of this study was to investigate the endoscopic and histologic predictors of enteric infection in patients with IBD and an exacerbation in symptoms using a multiplex PCR-based stool test for 22 pathogens. We reviewed the records of 691 patients with IBD who underwent a gastrointestinal pathogen panel PCR stool test (GI PCR; BioFire FilmArray) during an exacerbation of symptoms between January 2015 and May 2017. We identified patients who underwent endoscopy within 30 days of the test and collected baseline characteristics, PCR outcomes, medication exposures, and endoscopic and histologic findings. 77 patients underwent endoscopy within 30 days of a GI PCR test (Table 1). 26 (33.8%) were positive for 14 enteric pathogens with E.coli species (14, 42.4%) and Norovirus (5, 15.2%; Table 2) as the most common. Endoscopic esophagitis was more common in patients with a positive test (p=0.04), but there were no other predictors of an infection including ileitis (p=0.43) and colitis (p=0.58) on endoscopy or chronicity (p=0.21), architectural distortion (p=0.65), and granulomas (p=0.46) on histology. These findings did not differ between viruses and bacteria. Of patients who tested positive, 12 (46.2%) received antibiotics. Patients who tested negative were more likely to have IBD medications added or up-titrated (p=0.004). Endoscopic and histologic findings did not differentiate flare of IBD from enteric infection. Our results suggest that these entities may elicit similar endoscopic and histologic findings, or coexist, and PCR stool testing may identify potential pathogens. As PCR testing significantly impacted management, further study is required to evaluate the impact of various enteric infections on the course of IBD and treatment strategies following GI PCR testing.

PREGNANCY IN ACUTE AND CHRONIC ULCERATIVE COLITIS: CASE REPORTS

Ulcerative colitis is an autoimmune idiopathic chronic relapsing inflammatory bowel disease involving the mucosa and thesubmucosa of the large bowel starting at the rectum. Acute disease occurring for the first time in pregnancy is not common and hasthe Truelove and Witt’s criteria for defining acute ulcerative colitis. Acute ulcerative colitis in pregnancy is difficult to diagnoseand carries the risk of pre-term birth as well as fetal growth restriction along with fetal malformations if not treated aggressively.Drugs and investigations safe in pregnancy along with appropriate care of the patient can improve the pregnancy outcome andpatient’s health. Chronic ulcerative colitis patients have exacerbations in pregnancy or early postpartum. These patients may havepoor absorption in spite of proper medication and have difficulty in building up the hemoglobin levels during pregnancy. Here, weare reporting two cases, one each of acute as well as chronic ulcerative colitis in pregnancy with their investigations, treatment, andoutcome in respect to maternal health during the entire pregnancy as well as fetal growth and complications.

Elevation of serum pyruvate kinase M2 (PKM2) in IBD and its relationship to IBD indices

ObjectivesEndoscopy remains the gold standard to diagnose and evaluate inflammatory bowel disease (IBD) activity. Current biomarkers or their combinations cannot adequately predict IBD risk, diagnosis, progression or relapse, and response to therapy. Pyruvate kinase M2 (PKM2) is emerging as a significant mediator of the inflammatory process. We aimed to assess levels of serum PKM2 in healthy and newly diagnosed IBD patients and its relationship with IBD indices and microbiota changes. Design and methodsIBD serum samples from newly diagnosed patients were collected and analyzed using a PKM2-ELISA and correlated with disease activity scores, IBD disease type, and intestinal microbiota. Furthermore, we tested the genetic and protein expression of PKM2 in an in vitro intestinal cell model of inflammation. ResultsSerum PKM2 levels were 6-fold higher in IBD patients compared to healthy controls, with no sensitivity to disease phenotype (Crohn's Disease or Ulcerative Colitis) or localization of inflammation. Serum PKM2 had considerably less interindividual variability than established IBD fecal biomarkers. A positive Pearson correlation (r=0.6121) existed between serum PKM2 and Bacteroidetes fecal levels in Crohn's disease (CD), while a negative (r=−0.6128) correlation was observed with Actinobacteria fecal levels. Furthermore, LPS (500ng/mL) significantly increased PKM2 expression in vitro, which was significantly suppressed by an anti-inflammatory flaxseed bioactive agent. ConclusionOur data suggests PKM2 as a putative biomarker for IBD and the dysbiosis of microflora in CD. Investigations involving larger number of clinical patients are necessary to validate its use as a serum biomarker of IBD.

Rare occurrence of inflammatory bowel disease in a cohort of Han Chinese ankylosing spondylitis patients- a single institute study

Despite a high prevalence of ankylosing spondylitis (AS) in Han Chinese, the clinical experience remains very limited in the extra-articular presentation of inflammatory bowel disease (IBD). A monocentric retrospective study was performed for the AS-associated IBD manifestation. This study analyzed AS patients fulfilling the 1984 revised New York diagnostic criteria, excluding those who had the onset of IBD before or concurrently with the diagnosis of AS, for their demographic, clinical, laboratory, radiological, pathological and medication data, particularly in the usage of anti-TNF monoclonal antibody. Among 988 AS patients with 19.8% female, 4 (0.4%) had the overt IBD presentation, one female and 3 male aged 28 to 47 years (38.8 ± 4.6), all ulcerative colitis with the characteristic histopathological findings. At the onset of colitis, all had a long-term disease duration of 10 to 25 years (17.5 ± 6.5) and high BASDAI 7.5 to 8.8 (8.2 ± 0.5) with the hip joint involvement. There were recurrent flares of colitis despite the treatment with corticosteroids and messalazopyrin/salazopyrin, and no relapses of IBD were observed for 6.0 ± 1.1 years after the adalimumab (ADA) therapy. In this retrospective cohort, we demonstrate the rarity of AS-associated IBD manifestation in Han Chinese with a beneficent effect from the ADA therapy.

Overview of paediatric IBD

Inflammatory bowel disease (IBD) is a chronic complex disease of children and adults requiring a range of medications and surgical techniques to induce and maintain remission. In common with other immune-mediated inflammatory disorders, it has shown an ever-increasing rise in incidence worldwide over the last 50 years. The cause of IBD arises from interactions between the microbiome in the gut and the gastrointestinal and systemic immune system in genetically susceptible persons, and with environmental triggers to both develop IBD and have relapses of IBD. The burden of IBD in children and adolescents can be high, and treatment needs a multi-disciplinary approach aiming to abolish symptoms, promote growth and development, and support a restriction-free life. Achieving healing of the intestinal mucosa promotes long-term remission and helps to avoid disease complications.

Heme Oxygenase-1 Induction and Anti-inflammatory Actions of Atractylodes macrocephala and Taraxacum herba Extracts Prevented Colitis and Was More Effective than Sulfasalazine in Preventing Relapse.

Background/AimsIn inflammatory bowel disease (IBD), repeated bouts of remission and relapse occur in patients and can impose a risk of colitis-associated cancer. We hypothesized that plant extracts of Atractylodes macrocephala (AM) or Taraxacum herba (TH) may be better than sulfasalazine for treating this disease because these extracts can promote additional regeneration.MethodsMurine intestinal epithelial IEC-6 cells were pretreated with AM or TH before a lipopolysaccharide (LPS)-induced challenge. Acute colitis was induced with 7 days of dextran sulfate sodium (DSS) in male C57BL/6 mice, and extracts of AM and TH were administered for 2 weeks before DSS administration.ResultsIn vitro studies demonstrated that AM or TH treatment reduced LPS-induced COX-2 and tumor necrosis factor-α mRNA levels but increased heme oxygenase-1 (HO-1). Oral preadministration of AM and TH rescued mice from DSS-induced colitis by inhibiting inflammatory mediators via inactivated extracellular signal regulated kinase and repressed nuclear factor κB and signal transducer and activator of transcription 3, but the effect was weaker for sulfasalazine than that for the extracts. Anti-inflammatory activities occurred via the inhibition of macrophage and T lymphocyte infiltrations. Unlike sulfasalazine, which did not induce HO-1, TH extracts afforded significant HO-1 induction.ConclusionsBecause the AM or TH extracts were far superior in preventing DSS-induced colitis than sulfasalazine, AM or TH extracts can be considered natural agents that can prevent IBD relapse.

Enteric Infection in Relapse of Inflammatory Bowel Disease: The Utility of Stool Microbial PCR Testing.

The similar presentations in relapse of inflammatory bowel disease (IBD) and enteric infection pose substantial barriers to diagnosis and treatment. The objective of this study was to investigate the incidence, etiology, predictors, and treatment of enteric infection in patients with IBD. We reviewed the records of 214 patients with IBD who underwent 295 gastrointestinal pathogen panel and Clostridium difficile infection (CDI) polymerase chain reaction (PCR) stool tests during an exacerbation of symptoms. We collected baseline characteristics, PCR outcomes, and medication exposures. We tested for associations via the Chi-square test and the t-test. Logistic regression analysis was used to identify predictors of enteric infection. Of 295 PCR tests ordered during an exacerbation of symptoms, 38 (12.9%) were positive for CDI and 41 (13.8%) were positive for 14 other pathogens, with E. coli species as the most common. A previous history of CDI or colonic involvement of IBD predicted CDI, whereas a previous colectomy predicted negative testing for CDI. The majority with CDI (24, 63.2%) received oral vancomycin and 15 (37.5%) with other enteric pathogens were treated for their infection. Patients with CDI had a longer median length of hospital stay (8.5 versus 4 days, P = 0.041). Patients who tested negative for enteric infections were more likely to have IBD medications added or up-titrated (P = 0.027). Enteric infection was detected in 79 (26.8%) symptomatic patients with IBD , with CDI the most frequent followed by E. coli. Negative stool PCR testing was associated with changes in IBD management. Broad enteric PCR testing should be considered during relapse of IBD.

Clinical Utility of Fecal Calprotectin Monitoring in Asymptomatic Patients with Inflammatory Bowel Disease: A Systematic Review and Practical Guide.

In asymptomatic patients with inflammatory bowel disease (IBD), "monitoring" involves repeated testing aimed at early recognition of disease exacerbation. We aimed to determine the usefulness of repeated fecal calprotectin (FC) measurements to predict IBD relapses by a systematic literature review. An electronic search was performed in Medline, Embase, and Cochrane from inception to April 2016. Inclusion criteria were prospective studies that followed patients with IBD in remission at baseline and had at least 2 consecutive FC measurements with a test interval of 2 weeks to 6 months. Methodological assessment was based on the second Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) checklist. A total of 1719 articles were identified; 193 were retrieved for full text review. Six studies met eligibility for inclusion. The time interval between FC tests varied between 1 and 3 months. Asymptomatic patients with IBD who had repeated FC measurements above the study's cutoff level had a 53% to 83% probability of developing disease relapse within the next 2 to 3 months. Patients with repeated normal FC values had a 67% to 94% probability to remain in remission in the next 2 to 3 months. The ideal FC cutoff for monitoring could not be identified because of the limited number studies meeting inclusion criteria and heterogeneity between selected studies. Two consecutively elevated FC values are highly associated with disease relapse, indicating a consideration to proactively optimize IBD therapy plans. More prospective data are necessary to assess whether FC monitoring improves health outcomes.

Clinical presentation of immune-related colitis associated with PD-1 inhibitor monotherapy (MONO) and combination PD-1/CTLA-4 inhibitors (COMBO) in melanoma.

9566 Background: Ipilimumab-related colitis has been well described, but the clinical presentation of colitis related to MONO or COMBO therapy has not. We aimed to characterize clinical features that define this serious adverse event. Methods: This retrospective study included melanoma pts with colitis screened from 6 academic centers treated with either MONO or COMBO therapy. Clinically relevant colitis was defined as diarrhea/colitis symptoms requiring systemic steroids. The onset, management, and outcomes related to colitis were summarized. Results: We screened 866 pts and identified 72 with clinically relevant colitis. For the MONO cohort, the incidence was 3.5% (23/657) and 23.4% (49/209) in the COMBO cohort. MONO-colitis occurred at a median 33 weeks (wks) into therapy, while median onset was 8 wks with COMBO therapy. One pt had grade 5 colitis from COMBO therapy. Despite the use of systemic steroids, COMBO-colitis needed more infliximab therapy (38.8% vs 26.1%). The median prednisone equivalent dose was higher for COMBO therapy (1.5 vs 1 mg/kg), and the median taper was shorter for MONO-colitis (4 vs 6 wks). Steroid dose-escalation for worsening symptoms during taper was more common with COMBO-colitis (42.9% vs 17.3%). Relapse was similar between cohorts (MONO: 26.1%, COMBO: 20.4%). Relapses occurred more frequently in COMBO therapy with tapers shorter than the median (38.1% vs 25.0%), and more frequently in MONO therapy with steroid doses lower than the median (60% vs 21.7%). MONO-colitis pts (17.4%) were less likely than COMBO-colitis pts (46.9%) to be restarted on PD-1 therapy. When restarted, only 13% with COMBO therapy relapsed as compared to 50% with MONO therapy. Objective response rates for MONO and COMBO cohorts were 72.7% and 56.1%, respectively. Conclusions: Colitis occurred with a much higher incidence in COMBO therapy. MONO-colitis was associated with a milder course with later onset, shorter duration and lower dose of steroids, fewer dose-escalations, and need for infliximab as compared to COMBO therapy. Relapse of colitis was generally associated with shorter steroid tapers for COMBO therapy and lower steroid doses for MONO therapy.

5 Outcomes following ANTI-TNF discontinuation and the risk of relapse in inflammatory bowel disease; a single centre experience

Background Crohn’s disease (CD) and Ulcerative Colitis (UC) are chronic inflammatory bowel (IBD) conditions that result in fluctuations of disease activity. Infliximab and Adalimumab are well-established agents associated with inducing and maintaining remission in IBD. Long term use of this agent has an associated risk profile and significant healthcare budget implications. Aims The aim was to identify patients in remission suitable for discontinuation of anti-TNF therapy and follow their clinical course to identify the patients who maintained a clinical remission Methods A single centre retrospective of our 1000 IBD patients. We reviewed IBD cohort on Anti TNF therapy. Analysis of colonoscopy findings and patient symptoms at time of discontinuation was performed and subsequent clinical follow following withdrawal of therapy. Results We identified 65 patients on Infliximab. 37 (57%) have UC and 28 (43%) have CD. Following a mean treatment interval of 41 months Infliximab therapy was discontinued in 19 (29%) patients. Of the discontinuation cohort 11 (58%) patients had UC, 6 (31.5%) had CD 2 (10.5%) were indeterminate colitis. During a follow up of 36 months 18 (95%) remained in clinical remission, while 1 (5%) relapsed. We identified 198 patients on Adalimumab in our cohort for treatment of CD. Of this cohort 3 (1.5%) were discontinued as they were in clinical remission. The follow up for this arm was 50 months. There have been 2 (66%) relapses in this group. Conclusions Successful remission was achieved in 95% of our Infliximab cohort and 33% of our Adalimumab cohort resulting in fewer hospital admissions, improvement in patient quality of life and decreased healthcare costs that are associated with provision of both maintenance and rescue therapy for flares of disease.

Cytomegalovirus colitis in hospitalized inflammatory bowel disease patients in Taiwan: a referral center study

BackgroundColitis is exacerbated in patients with concurrent cytomegalovirus (CMV) infection and inflammatory bowel disease (IBD). We assessed the prevalence and clinical features of CMV colitis in hospitalized IBD patients.MethodsA retrospective study reviewed the data from January 1, 1998 through December 31, 2013 compiled at the National Taiwan University Hospital. The CMV colitis patients’ demographic data, clinical information, treatment regimens, pathologic findings, and outcome were analyzed.ResultsA total of 673 IBD patients were hospitalized during the study period. There were 312 patients diagnosed with Crohn’s disease (CD) and 361 with ulcerative colitis (UC). CMV colitis was diagnosed as having positive inclusion bodies in colonic tissue. Six of the 312 CD patients (1.9%) and five of the 361 UC patients (1.4%) were diagnosed with CMV colitis. Compared to CD patients without CMV colitis, patients with CMV colitis were more often older (p < 0.005). Higher steroid usage was noted in the CMV positive group compared to age and gender matched CMV negative IBD patients (81.8% vs. 51.5%). Eight patients received ganciclovir treatment. Three patients who did not receive antiviral treatment had colitis flare-ups after the index admission.ConclusionsThe prevalence of CMV colitis in hospitalized IBD inpatients was 1.6% in Taiwan. Two associated factors for CMV colitis in hospitalized IBD patients were that they were elderly in CD and were on higher doses of steroids. Routine histopathology studies and/or PCR for refractory colitis patients are suggested to diagnose CMV colitis. Once the diagnosis is made, antiviral treatment is recommended to decrease the colitis relapse rate.

Raised faecal calprotectin is associated with subsequent symptomatic relapse, in children and adolescents with inflammatory bowel disease in clinical remission.

Reliable data on inflammatory biomarkers for predicting relapse of paediatric inflammatory bowel disease (IBD) are lacking. To investigate the predictive value of faecal calprotectin (FC) and CRP for symptomatic relapse in pediatric IBD in clinical remission. In this cross-sectional cohort study, patients <18 years with Crohn's disease or ulcerative colitis in clinical remission ≥3 months were included. At baseline, clinical and biochemical disease activity were assessed using the abbreviated-Pediatric Crohn's Disease Activity Index or Pediatric Ulcerative Colitis Activity Index, and FC and CRP respectively. Disease course over the subsequent 12 months was retrospectively assessed. In total, 114 patients (56% males; median age 14.9 years) were included. Baseline FC was higher in patients that developed symptomatic relapse [median (IQR), relapse 370 μg/g (86-1100) vs. remission 122 μg/g (40-344), P = 0.003]. Baseline FC was predictive of symptomatic relapse within 6 months [HR per 250 μg/g (95% CI): 1.46 (1.21-1.77), P < 0.001], with good predictive accuracy (AUC: 0.82). Optimal FC cut-off was 350 μg/g, with positive and negative predictive value of 41% and 96%. Baseline CRP was higher in patients that developed symptomatic relapse [median (IQR), relapse 1.0 μg/g (0.6-5.0) vs. remission 1.0 μg/g (0.4-2.0), P = 0.033]. Baseline CRP was predictive of symptomatic relapse within 6 months from baseline [HR per 1 mg/L (95% CI): 1.10 (1.02-1.19), P = 0.011], with fair predictive accuracy (AUC: 0.72). Optimal CRP cut-off was 1.0 mg/L, with positive and negative predictive value of 21% and 94%. Faecal calprotectin and CRP are predictive of symptomatic relapse and may be valuable in management of paediatric IBD in clinical remission.