Adult Crohn's Disease Patients Research Articles

P109 Analysis of the clinical, gastroscopic, and pathological features of upper gastrointestinal lesions in Crohn’s disease

With the increasing incidence of Crohn's disease (CD) of the upper gastrointestinal (UGI) tract, whether gastroscopy should be routinely performed in asymptomatic adult CD patients is controversial. We aimed to assess the prevalence of UGI involvement, determine the role of gastroscopy in the diagnosis, and assess whether UGI symptoms should be used as guidelines for gastroscopy. This cross-sectional study included consecutive patients diagnosed with CD at our centre between June 2017 and May 2018. gastroscopies and histological reviews were performed by designated endoscopists and pathologists. Ten specimens were obtained from six areas of the UGI tract (the oesophagus, gastric body, antrum and angulus, duodenal bulb, and descending duodenum). Both demographic and clinical data were collected. Among the 169 included patients, endoscopic and histological lesions suspected to be of UGI CD were found in 74 (43.79%) and 106 (62.72%) patients, respectively. Seven (4.14%) patients had non-caseating granulomas, 15 (8.88%) patients had focally enhanced gastritis, and 36 (21.3%) patients had focal active gastritis. 137 (81.1%) patients had no UGI symptoms, among these, endoscopic and/or pathological abnormalities were observed in 108 (78.8%) patients. Twenty-four (75%) patients with UGI symptoms did not have any endoscopic or histological abnormalities. In total, the rates of non-caseating granulomas, focally enhanced gastritis, and focal active inflammation were significantly higher in the asymptomatic group (p = 0.033). According to the endoscopic and histological features, 26 patients (15.4%) were identified having UGI CD involvement among 169 CD patients, and among these, 24 patients (17.5%) were asymptomatic, whereas 2 (6.3%) were symptomatic. We further observed that the frequency of characteristic histological lesions was significantly higher in the gastric antrum and angulus than in any other biopsy site (p = 0.028). Focally enhanced gastritis and focal active inflammation had significantly higher frequencies than non-caseating granulomas in the stomach (p < 0.01). There were no significant differences in the basic data between patients with or without endoscopic or pathological abnormalities (p > 0.05). There was a high frequency of UGI involvement in adult CD patients, irrespective of the presence or absence of UGI symptoms. Confirmable characteristic UGI lesions of CD are also common, and routine gastroscopy and biopsy may be recommended for patients suspected of having or diagnosed with CD. Focally enhanced gastritis and focal active inflammation were observed to be more common than non-caseating granulomas which may helpful in the diagnosis of CD and are worth focussing on.

Early Postoperative Anti-TNF Therapy Does Not Increase Complications Following Abdominal Surgery in Crohn's Disease.

The impact of postoperative anti-TNF therapy on infectious complications following Crohn's disease surgery remains controversial. Use of anti-TNF therapy 2-4weeks postoperatively appears safe, but safety of use within 2weeks is unknown. We sought to evaluate the effect of anti-TNF therapy initiated within 2weeks of abdominal surgery in patients with Crohn's disease. We conducted a retrospective review of adult Crohn's disease patients undergoing abdominal surgery between 2004 and 2011. Infectious and non-infectious complications were compared between patients exposed to anti-TNF therapy within 2weeks or between 2 and 4weeks postoperatively and to those without exposure using chi-squared and regression analysis. Three hundred thirty-one abdominal surgeries were included; 241 were without anti-TNF exposure, 46 received postoperative anti-TNF within 2weeks of surgery, and 44 received anti-TNF therapy 2-4weeks after surgery. Patients who received anti-TNF therapy within 2weeks of surgery, those initiated between 2 and 4weeks of surgery, and those who did not receive anti-TNF therapy within 4weeks of surgery had no significant difference in rates of infectious complications (22%, 32%, 33%, p = 0.332). Rates of non-infectious complications (4%, 9%, 14%, p = 0.143), mortality (0%, 0%, 3%, p = 0.105), hospital readmission (17%, 16%, 15%, p = 0.940), and reoperation (11%, 11%, 16%, p = 0.563) were also similar between groups. Use of early anti-TNF therapy within 2weeks or between 2 and 4weeks following abdominal surgery did not increase risk of postoperative surgical infections in Crohn's patients.

Isolated colonic Crohn's disease is associated with a reduced response to exclusive enteral nutrition compared to ileal or ileocolonic disease

Exclusive enteral nutrition (EEN) as a primary therapy is safe and effective for inducing the clinical remission of active luminal Crohn's disease (CD). Whether isolated colonic involvement affects the efficacy of EEN is controversial. We aimed to identify the influence of isolated colonic CD on the efficacy of EEN and to determine other potential predictors of the response to induction therapy with EEN in adult patients with CD. Data for adult CD patients treated with EEN as an induction therapy at our centre from January 1, 2014, to May 31, 2017, were reviewed. Eligible patients were divided into an isolated colonic Crohn's disease (cCD) group and a non-isolated colonic Crohn's disease (non-cCD) group according to the disease location. The rates of clinical remission and inflammatory and nutritional serum markers were compared between the groups. Possible relationships between isolated colonic involvement or other potential factors and the efficacy of EEN were assessed by univariate and multivariate analyses. The propensity score matching method was used to confirm the results. Overall, 241 patients were included in the analysis: 52 patients in the cCD group and 189 patients in the non-cCD group. The rates of clinical remission differed between the two groups (cCD group: 51.9% versus non-cCD group: 68.3%, P=0.029). Multivariate analyses indicated that isolated colonic involvement was associated with a reduced response to EEN (OR=2.74; [CI] 95%=[1.2-6.23], P=0.016). Additionally, the lean body mass index (LBMI) before treatment was associated with the efficacy of EEN (OR=0.636; [CI] 95%=[0.444-0.912], P=0.014). These associations were confirmed using the propensity score model. For patients with isolated colonic CD, multivariate analysis showed that pancolitis (OR=16.7; [CI] 95%=[1.074-260.5], P=0.044) was another independent factor for the efficacy of EEN. Further analysis showed that even in patients who achieved clinical remission after EEN, inflammatory serum markers declined more slowly in the cCD group than in the non-cCD group, and the time to remission was longer in the cCD group. Isolated colonic CD showed a reduced response to induction therapy with EEN compared with ileal or ileocolonic disease in adult patients. Patients with isolated colonic CD required more time to benefit from EEN therapy compared with patients with non-colonic CD. Additionally, LBMI before treatment was associated with the efficacy of EEN.

Real-world clinical, endoscopic and radiographic efficacy of vedolizumab for the treatment of inflammatory bowel disease.

Vedolizumab is an α4β7 integrin antagonist with proven efficacy for inducing and maintaining clinical response and remission in Crohn's disease (CD) and ulcerative colitis (UC). To evaluate clinical and objective response and remission rates with vedolizumab in a large, real world cohort. A retrospective cohort study of adult CD and UC patients receiving vedolizumab between 2012 and 2017 was conducted. clinical or objective response and remission at 3, 6 and 12months after induction. Clinical remission was defined by complete, steroid-free absence of symptoms. Objective remission was defined by endoscopic mucosal healing or normalisation of radiographic appearance on contrast-enhanced ultrasound or CT/MR enterography. The study included 222 vedolizumab patients (122 CD, 100 UC). In CD, clinical remission at 3, 6 and 12months was achieved in 19.8% (22/111), 22.1% (21/95) and 22.1% (15/68) of patients, respectively. Objective remission occurred in 11.5% (6/52), 21.2% (14/66), and 18.9% (7/37) of patients at 3, 6 and 12months, respectively. In UC, clinical remission at 3, 6, and 12months was 51.0% (51/100), 61.8% (55/89) and 61.9% (39/63), respectively. Endoscopic remission occurred in 27.5% (11/40), 41.0% (16/39) and 47.8% (22/46) of patients at 3, 6 and 12months, respectively. In multivariable analysis, patients with UC as compared to CD, and those with milder disease activity were more likely to achieve objectively defined remission at both 6 and 12months. Vedolizumab was effective for induction and maintenance of clinical and objective remission, both in Crohn's disease and ulcerative colitis.

Clinical Benefit of Capsule Endoscopy in Crohn's Disease: Impact on Patient Management and Prevalence of Proximal Small Bowel Involvement.

Ileocolonoscopy and computed tomography (CT) or magnetic resonance (MR) enterography (CTE/MRE) are utilized to evaluate patients with small bowel (SB) Crohn's disease (CD). The purpose of our study was to estimate the impact of capsule endoscopy (CE) on patient management after clinical assessment, ileocolonoscopy, and CTE/MRE. We prospectively analyzed 50 adult CD patients without strictures at clinically indicated ileocolonoscopy and CTE/MRE exams. Providers completed pre- and post-CE clinical management questionnaires. Pre-CE questionnaire assessed likelihood of active SBCD and management plan using a 5-point level of confidence (LOC) scales. Post-CE questionnaire assessed alteration in management plans and contribution of CE findings to these changes. A change of ≥2 on LOC scale was considered clinically meaningful. Of the 50 patients evaluated (60% females), median age was 38 years, median disease duration was 3 years, and median Crohn's Disease Activity Index (CDAI) score was 238 points. All CTE/MRE studies were negative for proximal disease. CE detected proximal disease in 14 patients (28%) with a median Lewis score of 215 points. CE findings altered management in 17 cases (34%). The most frequent provider-perceived benefits of CE were addition of new medication (29%) and exclusion of active SB mucosal disease (24%). CE is a safe imaging modality that alters clinical management in patients with established SBCD by adding incremental information not available at ileocolonoscopy and cross-sectional enterography.

Efficacy of a concomitant elemental diet to reduce the loss of response to adalimumab in patients with intractable Crohn's disease.

Secondary loss of response to adalimumab (ADA-LOR) commonly occurs in patients with Crohn's disease (CD) treated with adalimumab (ADA). We evaluated the efficacy of concomitant elemental diet (ED) therapy to reduce ADA-LOR in adult CD patients. Patients were divided into either an ED (≥900kcal/day) or a non-ED group (<900kcal/day). Cumulative non-ADA-LOR rates were compared between groups. The effects of ED intake to reduce ADA-LOR were also assessed in antitumor necrosis factor-alpha (TNF-α)-naïve and infliximab (IFX)-intolerant or refractory CD patients. Serum ADA and TNF-α levels were measured. We enrolled 117 CD patients into the ED (n=25) or non-ED (n=92) groups. Although the cumulative non-ADA-LOR rate was higher in the ED group than in the non-ED group, ED intake was not an independent reducing factor for ADA-LOR (adjusted hazard ratio=0.725; 95% confidence interval: 0.448-1.180; P=0.196) in all patients. ED intake was significantly more effective in reducing ADA-LOR in IFX-intolerant or refractory patients than in anti-TNF-α-naïve patients in a dose-related manner (P for interaction <0.20). Serum ADA levels did not differ between the groups. Serum TNF-α levels were significantly lower in the ED group than in the non-ED group at week 28 (P=0.044) and week 52 (P=0.043). Concomitant ED therapy reduced ADA-LOR in IFX-intolerant or refractory patients in a dose-related manner. Reductions in the TNF-α levels by concomitant ED intake may contribute to reduce ADA-LOR in CD patients.

Daily hassles score associates with the somatic and psychological health of patients with Crohn's disease.

To examine the associations of daily hassles with the somatic and psychological health of Crohn's disease (CD) patients. A cross-sectional study of 400 self-selected adult CD patients was performed with completion of demographic, medical, and psychosocial questionnaires: economic status; Patient Harvey-Bradshaw Index of disease activity; Daily Hassles Scale (DHS); Short Inflammatory Bowel Disease Questionnaire (SIBDQ) and Short-Form Health Survey (SF-36 Physical and Mental Health) quality of life measures; Brief Symptom Inventory of psychological stress with summary Global Severity Index (GSI); Family Assessment Device; and List of Threatening Life Experiences. Analyses included correlations, regressions, and Sobel test statistic. The patients were aged 38.7 ± 14.1 years, 61% female and 67% working. The Patient Harvey-Bradshaw Index was 5.52 ± 4.87. The DHS was 88.0 ± 23.2, similar in men and women, higher in smokers, and increased with greater disease activity (p<.001). The most commonly reported hassles were time, social, and work. DHS had significant negative correlations with age, disease duration, and economic status and positive correlations with GSI, SF-36, and SIBDQ. An increased Daily Hassles score was associated with reduced SIBDQ (p<.001) and SF-36 Mental Health (p<.001) and increased GSI (p<.001) and Patient Harvey-Bradshaw Index (p<.001). This effect of DHS on Patient Harvey-Bradshaw Index was mediated by GSI (Sobel t=6.09, p<0.001). Daily hassles in CD patients are shown for the first time to be associated with increased psychological stress and disease activity and reduced quality of life and lower economic status. This has psychotherapeutic implications.

Surgical Rates for Crohn's Disease are Decreasing: A Population-Based Time Trend Analysis and Validation Study.

Objectives:Temporal changes for intestinal resections for Crohn’s disease (CD) are controversial. We validated administrative database codes for CD diagnosis and surgery in hospitalized patients and then evaluated temporal trends in CD surgical resection rates.Methods:First, we validated International Classification of Disease (ICD)-10-CM coding for CD diagnosis in hospitalized patients and Canadian Classification of Health Intervention coding for surgical resections. Second, we used these validated codes to conduct population-based surveillance between fiscal years 2002 and 2010 to identify adult CD patients undergoing intestinal resection (n=981). Annual surgical rate was calculated by dividing incident surgeries by estimated CD prevalence. Time trend analysis was performed and annual percent change (APC) with 95% confidence intervals (CI) in surgical resection rates were calculated using a generalized linear model assuming a Poisson distribution.Results:In the validation cohort, 101/104 (97.1%) patients undergoing surgery and 191/200 (95.5%) patients admitted without surgery were confirmed to have CD on chart review. Among the 116 administrative database codes for surgical resection, 97.4% were confirmed intestinal resections on chart review. From 2002 to 2010, the overall CD surgical resection rate was 3.8 resections per 100 person-years. During the study period, rate of surgery decreased by 3.5% per year (95% CI: −1.1%, −5.8%), driven by decreasing emergent operations (−10.1% per year (95% CI: −13.4%, −6.7%)) whereas elective surgeries increased by 3.7% per year (95% CI: 0.1%, 7.3%).Conclusions:Overall surgical resection rates in CD are decreasing, but a paradigm shift has occurred whereby elective operations are now more commonly performed than emergent surgeries.

Risk Factors for Rescue Therapy in Crohn's Patients Maintained on Infliximab After Withdrawal of the Immunomodulator: A Long-Term Follow-Up.

Usefulness of thiopurine and scheduled infliximab combination therapy in non-immunomodulator (IM)-naïve Crohn's disease (CD) patients and theoptimal length of dual therapy are still debated. To determine proportion of patients developing disease flare requiring rescue therapy and risk factors associated with disease flare after de-escalation of IM from combination therapy. Adult CD patients in clinical remission on combination therapy were identified from a large single-center database between 2002 and 2009. Patients who had their IM stopped in the absence of adverse events were included. Association between clinical and demographic variables and time until rescue therapy was analyzed using Cox-proportional hazard models. Forty-three CD patients on combination therapy in clinical remission at time of IM de-escalation were identified and followed up for a median duration of 61.6months (range 5.4-129.5). Median duration of remission on combination therapy prior to IM de-escalation was 12.0months (range 4-74). Thirty-one patients (72.1%) required rescue therapy during follow-up. On multivariable analysis, age at diagnosis <16years versus >40years (HR 4.55, 95% CI 1.18-17.62, p=0.028), using methotrexate instead of azathioprine in combination with infliximab (HR 3.37, 95% CI 1.14, 9.96, p=0.028), and duration of combination therapy <6months (HR 5.68, 95% CI 1.58, 20.36, p=0.007) increased risk forrescue therapy. A large proportion of CD patients on combination therapy experienced a flare following IM withdrawal. Young age at diagnosis, short duration of combination therapy, and methotrexate use were independent predictors of the need for rescue therapy.

Genetic Markers and Radiologic Disease Activity in Crohnʼs Disease: Results From a Cohort at a Tertiary Care IBD Referral Center

Introduction: Several studies have examined association between serologic/immunologic biomarkers and outcome parameters among Crohn's disease (CD) patients. Impact of serologic/immunologic biomarkers on CD outcomes is difficult to study due to their variability over time. Contrary to this, genotypes are time independent. We studied association between select IBD specific genetic markers and radiologic disease activity (RDA) in CD patients seen at a U.S. tertiary care IBD referral center. Methods: Adult CD patients >19 years followed for at least one year between 2014 and 2016 at our IBD center and tested for presence of ATG16L1, ECM1, NKX2-3 genotypes (associated with IBD) and absence of STAT3 genotype (associated with IBD) at initial observation were included. Radiologic data including CT/MR enterography and MRI/CT Abdomen and pelvis were reviewed. We performed univariate analyses to examine incidence rates of moderate to severely active radiologic disease among CD patients based on presence or absence of above genotypes. We built Generalized Poisson Regression Models (GPR) for Rate Data to estimate adjusted (for age, sex, race, duration of disease, steroid use, biologic use, methotrexate use, azathioprine use) incidence rate ratios (IRR) of radiologic active disease based on dichotomous assessment at each clinic visit among CD patients with presence vs. absence of selected IBD specific genotypes. Results: Of the 76 CD patients with available genetic markers, 54 were followed in clinic for at least one year. Of these, 45 (83%) had positive genotype ATG16L1, 28 (52%) had positive ECM1, 42 (78%) had NKX2-3 and 25 (46%) lacked STAT3 genotype respectively (Table 1). Among CD patients, incidence rate of radiologic active disease was 81.48 per 100 person-years for genotype ATG16L1, 90.63 per 100 person-years for genotype ECM1, 75.51 per 100 person-years for genotype NKX2-3, 86.21 per 100 person-years for absence of genotype STAT3. GPR Model for Rate Data when adjusted showed that CD patients with genotypes ATG16L1 (IRR 1.34, 95%CI 0.54 - 3.27) and ECM1 (IRR 1.12, 95%CI 0.54 - 2.33) had slightly higher rate of radiologic active disease during the observation period (Table 2). These associations did not reach statistical significance.Table: Table. Characteristic description of Crohn's disease patients by Genetic MarkersTable: Table. Rates and Rate Ratios of Crohn's Disease Related Radiologic Disease Activity (RDA)Conclusion: Presence of ATG16L1 and ECM1 genotypes may play a role in predicting radiologic active disease in CD. However, further study of these associations in larger samples is needed to better elucidate their overall impact on CD outcomes.

Development and Validation of a Multi-marker Serum Test for the Assessment of Mucosal Healing in Crohnʼs Disease Patients

Introduction: Mucosal healing (MH) has become the primary therapeutic target in Crohn's Disease (CD). Ileocolonoscopy, currently the gold standard for assessing MH, is invasive and time-consuming with poor patient acceptance. This limits the practical feasibility for serial monitoring of mucosal disease activity and response to treatment. We developed a serum-based, multi-analyte MH algorithm incorporating a panel of biomarkers associated with biological pathways important for mucosal homeostasis in CD patients. Methods: Retrospective serum samples were taken from adult CD patients at or within 30 days of ileocolonoscopy. A panel of serum proteomics biomarkers, selected from a total of 48 markers based on their correlation with endoscopic activity, were used to train a logistic regression model against visualized endoscopic disease severity determined by either CDEIS or SES-CD scores. The model was independently validated in a prospectively collected, centrally read, longitudinal cohort of 118 patients from the TAILORIX clinical trial. The final model utilized 13 biomarkers to produce a 0-100 scale termed as the Mucosal Healing Index (MHI). The markers represent multiple biological pathways thought to be involved in the MH process including angiogenesis (Ang1, Ang2), cell adhesion (CEACAM1, VCAM1), growth factor signaling (TGF||), inflammation (CRP, SAA1), matrix remodeling (mmp-1, -2, -3, -9 and EMMPRIN), and immune modulation (IL7). Results: A total of 748 samples from 396 patients (mean age: 34 years, 49% males, 26% ileal, 52% ileocolonic and 22% colonic disease) were used for the training and validation of the MH index. The overall accuracy of the test was 90% with a negative predictive value (NPV) of 92% for identifying patients in remission (CDEIS<3) or with mild (CDEIS 3-8) endoscopic disease (MHI range 0-40) and a positive predictive value (PPV) of 87% for identifying patients with endoscopic evidence of active disease (CDEIS ≥3; MHI range 50-100). 14% of the specimens fell within an intermediate zone (MHI 41-49) with an observed 78% probability of active disease. Test performance is shown in Table 1.Table: Table. Mucosal Healing Index Performance for Detecting Mucosal Disease Severity in CD PatientsConclusion: A peripheral blood-based test has been developed that can be used as a non-invasive surrogate for mucosal endoscopic activity assessed with ileocolonoscopy in CD patients. The incorporation of this test into current practice could aid in the management and monitoring of CD patients to help determine therapeutic efficacy in a treat to target paradigm.

Role of capsule endoscopy and fecal biomarkers in small-bowel Crohn's disease to assess remission and predict relapse

Capsule endoscopy (CE) is the most sensitive test to diagnose small-bowel Crohn's disease (CD). Conventional parameters poorly assess CD remission, and although fecal biomarkers assess colonic activity, their role in assessing remission is uncertain. We report CE findings in small-bowel CD patients in clinical remission compared with fecal biomarkers and standard clinical tools to determine mucosal remission and predict relapses. Forty-three adult small-bowel CD patients in clinical remission (Crohn's Disease Activity Index [CDAI]<150) were prospectively enrolled at 4 academic centers and followed clinically for 12 months. Baseline CE studies were scored using the Capsule Endoscopy Scoring Index (CESI or Lewis score). Baseline and endpoint fecal biomarkers were assayed. CE findings were normal in 17 patients (40%), mild inflammation in 19 (44%), and moderate to severe inflammation in 7 (16%). Of the 26 patients (60%) with mucosal inflammation on CE, 85% had elevated baseline fecal calprotectin and 77% elevated lactoferrin level. Calprotectin and lactoferrin were normal in all patients without inflammation and elevated in all with moderate to severe inflammation. CESI correlated significantly with calprotectin, lactoferrin, and S100A12 levels but not either CDAI or C-reactive protein. During follow-up, 14% of patients exhibited a clinical flare; all had mucosal inflammation at CE and 83% had elevated baseline calprotectin and lactoferrin levels. In small-bowel CD patients in clinical remission, many had ongoing mucosal inflammation assessed by CE and fecal biomarkers. Only some developed a clinical flare during medium-term follow-up. These findings suggest CE and fecal biomarkers are useful in monitoring small-bowel CD progress.

Analysis of SHIP1 expression and activity in Crohn's disease patients.

BackgroundSH2 domain containing inositol-5-phosphatase (SHIP1) is an important modulator of innate and adaptive immunity. In mice, loss of SHIP1 provokes severe ileitis resembling Crohn’s disease (CD), as a result of deregulated immune responses, altered cytokine production and intestinal fibrosis. Recently, SHIP1 activity was shown to be correlated to the presence of a CD-associated single nucleotide polymorphism in ATG16L1. Here, we studied SHIP1 activity and expression in an adult cohort of CD patients.MethodsSHIP1 activity, protein and mRNA expression in peripheral blood mononuclear cells from CD patients in clinical remission were determined by Malachite green assay, Western blotting and qRT-PCR respectively. Genomic DNA was genotyped for ATG16L1 rs2241880.ResultsSHIP1 protein levels are profoundly diminished in a subset of patients; however, SHIP1 activity and expression are not correlated to ATG16L1 SNP status in this adult cohort.ConclusionsAberrant SHIP1 activity can contribute to disease in a subset of adult CD patients, and warrants further investigation.

Antibiotics for induction and maintenance of remission in Crohn's disease

Antibiotics for induction and maintenance of remission in Crohn's disease

P441 Thalidomide induces clinical remission and mucosal healing in adults with active Crohn's disease: a prospective open-label study

Background: Thalidomide is effective in inducing clinical remission and longer-term maintenance of remission in children and adolescents with refractory Crohn's disease (CD). However, little is known about efficacy and safety of thalidomide therapy for adult CD patients—particularly with respect to mucosal healing. Methods: We conducted a prospective observational open-label study (ClinicalTrials.gov, NCT02501291) between January 2013 and April 2015. Forty-seven adult patients with active CD who were resistant or intolerant to corticosteroids and/or immunomodulators or biologics received 50–100mg of thalidomide daily. Primary outcome was clinical remission evaluated at week 8. Endoscopic assessment was performed at week 24 and defined as endoscopic response (decrease in CDEIS score >5 points from baseline CDEIS of 6 or more), endoscopic remission (CDEIS score <3) and mucosal healing (no ulceration). Results: The clinical remission rate was 14.9% and 23.4% at week 4 and 8, but increased to 46.8% at week 12 and 53.2% at week 24 out of all 47 included patients (intention-to-treat analysis). Out of the 47 patients, 32 consented and underwent ileocolonoscopy at week 24. The rate of endoscopic response and endoscopic remission were 68.4% and 43.8%. Mucosal healing (no ulceration) was achieved in 28.1% of patients. Adverse events occurred in 27 (57.4%, 27/47) patients but necessitated therapy discontinuation in only 5/47 (10.7%) of patients. Conclusions: Low-dose thalidomide was effective and tolerated for inducing and maintaining clinical remission in adult patients with active CD, but the optimal time frame for thalidomide to induce clinical remission may be longer than previously appreciated and is probably optimal at 12 weeks. Mucosal healing could be reasonably achievable with thalidomide.

P273 Prediction of treatment response in Crohn's disease patients using contrast enhanced ultrasound: a pilot study

Background: Increased vascularity of the bowel wall is an early pathologic change that occurs in patients with active Crohn's disease (CD) and is used in imaging methods with intravenous contrast. We investigated whether a baseline contrast-enhanced ultrasound (CEUS) can differentiate responders from non-responders treated medically over a period of 6 to 12 months. Methods: Unselected adult CD patients from a tertiary care IBD center were recruited. Baseline demographic and clinical data was gathered and CEUS was performed at baseline in patients using a second-generation US microbubble contrast agent (Definity®) using 0.2 ml as bolus followed by drip infusion at a fixed rate. Following placement of an ROI (region of interest) over the bowel wall, perfusion analysis software modeled time-intensity curves (TIC) and relative kinetic perfusion parameters were measured. In each patient, clinical activity, treatment and therapeutic outcome were assessed at 3, 6 and 12 months after the CEUS. Treatment changes after baseline, systemic steroid dependency, ongoing clinical activity, new disease complications and need for surgery during the observation period were considered treatment failures. CEUS parameters were compared in patients with active (aCD) versus inactive CD (aCD) at baseline and in patients with favorable versus poor outcome at 3, 6 and 12 months post CEUS. Results: Twenty-one patients (9 men, median age 32 years, median disease duration 13 years; 15 aCD and 12 with previous surgery) were recruited. Baseline kinetic CEUS parameters peak systolic velocity (PSV-wash in rate) & wash in/wash out area under curve (WiWoAUC) in bolus and drip infusion differed significantly in aCD (n=15) versus iCD patients (n=6), while there was no difference in bowel wall US features including peristalsis, vascularity, layers loss, submucosa echogenicity nor in CRP levels between the two groups (Table 2). At baseline, 8 patients were started on a new treatment or were escalated and 5 of them were non-responders at 6 months. There was a trend towards higher median values in baseline CEUS kinetic parameters (PSV and WiWoAUC) in responders versus non-responders (Table 2). Conclusions: CEUS is a potentially useful, non-invasive tool to identify patients with active CD and who are more likely to respond to therapy.

Surgery in Pediatric Crohn's Disease: Indications, Timing and Post-Operative Management.

Pediatric onset Crohn's disease (CD) tends to have complicated behavior (stricture or penetration) than elderly onset CD at diagnosis. Considering the longer duration of the disease in pediatric patients, the accumulative chance of surgical treatment is higher than in adult onset CD patients. Possible operative indications include perianal CD, intestinal stricture or obstruction, abdominal abscess or fistula, intestinal hemorrhage, neoplastic changes and medically untreatable inflammation. Growth retardation is an operative indication only for pediatric patients. Surgery can affect a patient's clinical course, especially for pediatric CD patient who are growing physically and mentally, so the decision should be made by careful consideration of several factors. The complex and diverse clinical conditions hinder development of a systemized treatment algorithm. Therefore, timing of surgery in pediatric CD patients should be determined with individualized approach by an experienced and well organized multidisciplinary inflammatory bowel disease team. Best long-term outcomes will require proactive post-operative monitoring and therapeutic modifications according to the conditions.

Diffusion-Weighted MR Enterography to Monitor Bowel Inflammation after Medical Therapy in Crohn's Disease: A Prospective Longitudinal Study.

ObjectiveTo prospectively evaluate the performance of diffusion-weighted imaging (DWI) to monitor bowel inflammation after medical therapy for Crohn's disease (CD).Materials and MethodsBefore and following 1–2 years of medical therapy, between October 2012 and May 2015, 18 randomly selected adult CD patients (male:female, 13:5; mean age ± SD, 25.8 ± 7.9 years at the time of enrollment) prospectively underwent MR enterography (MRE) including DWI (b = 900 s/mm2) and ileocolonoscopy. Thirty-seven prospectively defined index lesions (one contiguous endoscopy-confirmed inflamed area chosen from each inflamed anatomical bowel segment; 1–4 index lesions per patient; median, 2 lesions) were assessed on pre- and post-treatment MRE and endoscopy. Visual assessment of treatment responses on DWI in 4 categories including complete remission and reduced, unchanged or increased inflammation, and measurements of changes in apparent diffusion coefficient (ΔADC), i.e., pre-treatment–post-treatment, were performed by 2 independent readers. Endoscopic findings and CD MRI activity index (CDMI) obtained using conventional MRE served as reference standards.ResultsΔADC significantly differed between improved (i.e., complete remission and reduced inflammation) and unimproved (i.e., unchanged or increased inflammation) lesions: mean ± SD (× 10-3 mm2/s) of -0.65 ± 0.58 vs. 0.06 ± 0.15 for reader 1 (p = 0.022) and -0.68 ± 0.56 vs. 0.10 ± 0.26 for reader 2 (p = 0.025). DWI accuracy for diagnosing complete remission or improved inflammation ranged from 76% (28/37) to 84% (31/37). A significant negative correlation was noted between ΔADC and ΔCDMI for both readers with correlation coefficients of -0.438 and -0.461, respectively (p < 0.05).ConclusionDWI is potentially a feasible tool to monitor quantitatively and qualitatively bowel inflammation of CD after medical treatment.

Thalidomide is a therapeutic agent that is effective in inducing and maintaining endoscopic remission in adult CD patients

Previous studies have indicated that thalidomide may be effective in achieving clinical remission and response; however, there is a lack of studies on its effect in endoscopic remission. The aim of this study was to assess the efficacy and safety of thalidomide in inducing and maintaining endoscopic remission. A retrospective study was conducted in adult Crohn's disease (CD) patients treated with thalidomide. Patients were assessed based on their medical records. Endoscopy was performed after 4-6 months of thalidomide administration, and the simple endoscopic score for CD (SES-CD) was obtained. Twenty of the 21 (95.2%) eligible patients were recruited. Endoscopic remission was achieved in 7 of the 14 (50%) endoscopy active patients who received thalidomide treatment, whereas 10 (71.4%) patients showed an endoscopy response. The other 6 patients in endoscopic remission still maintained remission after thalidomide treatment. The SES-CD in endoscopy active patients was significantly reduced after thalidomide treatment (P<0.05). A total of 32 adverse events occurred in 17 of the 21 (81.0%) patients. Adverse events resolved spontaneously in 11 (64.7%) patients and resulted in treatment discontinuation and dose reduction in 4 (19.1%) and 2 (9.5%) patients, respectively. Thalidomide therapy is effective in inducing and maintaining endoscopic remission in adult CD patients. However, side effects may limit its clinical use in CD treatment.

Effect of psychosocial stressors on patients with Crohn's disease: threatening life experiences and family relations.

Threatening life experiences and adverse family relations are major psychosocial stressors affecting mental and physical health in chronic illnesses, but their influence in Crohn's disease (CD) is unclear. We assessed whether these stressors would predict the psychological and medical condition of CD patients. Consecutive adult CD patients completed a series of instruments including demography, Patient Harvey-Bradshaw Index (P-HBI), Short Inflammatory Bowel Disease Questionnaire (SIBDQ), short-form survey instrument (SF-36), brief symptom inventory (BSI), family assessment device (FAD), and list of threatening life experiences (LTE). Associations of FAD and LTE with P-HBI, SIBDQ, SF-36, and BSI were examined by multiple linear and quantile regression analyses. The cohort included 391 patients, mean age 38.38±13.95 years, 59.6% women, with intermediate economic status. The median scores were as follows: P-HBI 4 (2-8), FAD 1.67 (1.3-2.1), LTE 1 (0-3), SF-36 physical health 43.75 (33.7-51.0), SF-36 mental health 42.99 (34.1-51.9), and BSI-Global Severity Index 0.81 (0.4-1.4). The SIBDQ was 47.27±13.9. LTE was associated with increased P-HBI in all quantiles and FAD in the 50% quantile. FAD and LTE were associated with reduced SIBDQ (P<0.001). Higher LTE was associated with lower SF-36 physical and mental health (P<0.001); FAD was associated with reduced mental health (P<0.001). FAD and LTE were associated positively with GSI in all quantiles; age was associated negatively. CD patients with more threatening life experiences and adverse family relations were less healthy both physically and mentally. Physicians offering patients sociopsychological therapy should relate to threatening life experiences and family relations.