Severe Crohn's Disease Research Articles

P128 INCIDENCE AND OUTCOMES OF HOME PARENTERAL NUTRITION IN PATIENTS WITH CROHN’S DISEASE IN OMLSTED COUNTY, MINNESOTA, USA

Abstract Introduction Patients (pts) with Crohn’s disease (CD) undergoing multiple surgeries are at risk of extensive bowel resections, short bowel syndrome (SBS) and malnutrition and may need home parenteral nutrition (HPN). The aim of our study was to estimate the incidence of HPN use in pts with CD in a population-based cohort, and to assess clinical outcomes and complications associated with nutritional intervention. Methods This study was a retrospective population-based cohort using Rochester Epidemiology Project to identify pts who were diagnosed with CD between 1970 and 2011 in Olmsted County, MN. To identify the individuals who required HPN, these Pts were crossed against the list of those who enrolled in the local HPN program. Descriptive statistics were used to evaluate incidence and clinical outcomes. Results Four hundred twenty nine pts with CD were diagnosed in Olmsted County between 1970 and 2011. Of these, 14 received HPN between 1992 and 2018. The pts were followed for a median of 16.85 years after diagnosis of CD (interquartile (IQR), 12.25–24.70) and required HPN a median of 7.67 years after diagnosis (IQR,1.6–15.89). Among the 14 receiving HPN, 85.71% were females. Eleven (78.57%) had moderate to severe CD and 12 (85.71%) pts involved with fistulizing disease. Crohn’s disease involved the ileum in 92.86%, colon in 71.43%, and proximal GI in 14.29% of the pts. Thirteen (92.86%) pts underwent surgery primarily due to obstruction (84.62%). Other indication included: failure of medical therapy (46.15%), fistulizing disease (46.15%), severe pain (30.77%), abdominal abscess (23.08%), bleeding (15.38%), and necrosis (15.38%). Median number of bowel resections was 4 (range, 0–7). Twelve pts (85.71%) had a stoma placed. The median duration of HPN was 2.48 years (range, 0.11–16.36). Indications for HPN included SBS in 64.28%, malnutrition in 28.57% and bowel rest in 21.43%. The mean number of hospitalizations after the start of HPN was 5 (range, 0–20). Catheter-related bloodstream infections occurred in 10 (71.43%) pts, and 3 (21.43%) had a thrombosis. Four pts had osteoporosis and 2 had osteopenia. Parenteral nutrition-associated liver disease occurred in 2 (14.29%) of pts. The pts’ body weight increased a median of 2.5 kilograms (kg) 6 months after the start of HPN but decreased a median of 1 kg at 12 months. Four (30.77%) pts were on HPN at time of last follow-up. Five (35.71%) pts deceased mainly due to CD. Conclusion Less than 4% of pts with CD need HPN. Most pts on HPN have moderate to severe disease who have undergone extensive bowel resection with resultant SBS and malnutrition. Approximately 70% were able to discontinue HPN. Interestingly, after 6 months, pts lost most of the weight they gained during the first 6 months of HPN. It was possible that this was due to noncompliance, or increased metabolic needs because of active disease.

P655 Pharmacokinetics of ustekinumab in children and adolescents with moderately to severely active Crohn’s disease: Results from UniStar, a phase 1 study

Abstract Background Ustekinumab (UST) is approved for the treatment of adults with moderate to severe Crohn’s disease (CD) or ulcerative colitis. In the UniStar study, the pharmacokinetics (PK) of UST and its relationship with efficacy was evaluated in children who failed prior therapy. UniStar consisted of a PK portion (week 0–16) and extension (week 16–216); we report data through week 16. Methods UniStar is a multicentre, double-blind study (NCT02968108) designed to assess the PK, safety, and efficacy of UST in children (2–<18 years) with moderately to severely active CD, Paediatric CD Activity Index (PCDAI) score >30, and evidence of inflammation as measured by C-reactive protein >3.0 mg/l or faecal calprotectin >250 µg/g or ulcerations on ileocolonoscopy despite adequate treatment with corticosteroids and/or immunomodulators and/or anti-TNF therapies. Patients were randomised (1:1) and stratified by body weight (BW) and prior anti-TNF use for induction to one of 2 weight range-based IV doses: 130mg vs. 390 mg if BW ≥40 kg and 3mg/kg vs. 9 mg/kg if BW <40 kg. At week 8, all patients received a single subcutaneous (SC) UST maintenance dose of 90mg if BW ≥40 kg or 2 mg/kg if BW <40 kg. UST PK outcomes were assessed and compared with adult Phase 3 CD trials. Results 44 patients (59% ≥40 kg; >90% anti-TNF exposed) were randomised and treated with UST (n = 23 lower dose; n = 21 higher dose). Baseline demographics were generally similar between treatment groups. Most patients (67%) had a severe CD (PCDAI >40). At weeks 0 (1 h after infusion), 3, 6, and 8, mean serum UST concentrations (SUC) in the lower- (51.3, 7.7, 3.0, 1.6 μg/ml) and higher-dose groups (149.0, 23.7, 9.1, 4.8 μg/ml) were generally dose proportional (Figure 1a). Following SC UST at week 8, the impact of the difference in induction doses had diminished by week 16 when mean SUC was 1.5 µg/ml in the lower-dose group vs. 1.8 µg/ml in the higher-dose group. In the overall paediatric population (combined doses), serum UST concentrations were comparable to those in the reference adult CD studies (Figure 1b and c). In the higher dose group, we observed a pattern toward lower mean serum UST concentrations in patients weighing <40 kg vs. those weighing ≥40 kg; thus, UST should be dosed higher in patients <40 kg. Overall at week 8 and week 16, more patients achieved clinical response (PCDAI reduction ≥15) and biomarker improvement with higher UST concentrations, although this pattern was not observed for clinical remission (PCDAI ≤10; Figure 2). Conclusion Overall, UST PK was generally comparable between paediatric and adult patients with CD. A trend towards better efficacy outcomes with higher UST concentrations was observed in children similar to adults with CD.

DOP10 Intestinal ultrasound response and transmural healing after ustekinumab induction in Crohn’s disease: Week 16 interim analysis of the STARDUST trial substudy

Abstract Background Intestinal ultrasound (IUS) is a non-invasive tool for evaluating transmural disease activity in Crohn’s disease (CD) patients. We report interim Week (W)16 results from an IUS substudy of STARDUST, a phase 3B randomised trial of CD patients treated with ustekinumab (UST), comparing a treat-to-target (T2T) maintenance treatment strategy vs. standard of care (SoC). The aim of the substudy was to assess changes in IUS parameters, including transmural response to UST induction therapy. Methods Patients (≥18 years) with moderate–severe active CD (CD Activity Index [CDAI] 220–450 and simple endoscopic index for CD [SES-CD] ≥3) who failed conventional therapy and/or 1 biologic, received weight-based IV UST dosing of ~6mg/kg at Week 0, then SC UST 90mg at W8. At Week 16, patients with CDAI reduction ≥70 points were randomised (1:1) to T2T or SoC treatment arms. Exclusion criteria: characteristics precluding IUS visualisation of affected bowel segments and normal bowel wall thickness (BWT) (≤2.0mm terminal ileum; ≤3.0mm colon) for all segments at baseline (BL). Key IUS endpoints assessed at W4, W8 and W16 (central reading): IUS response ≥25% BWT reduction from BL; BWT change from BL (mm); IUS remission (transmural healing) ‒ BWT normalisation, colour Doppler signal ≤1, normal echo stratification, and absence of inflammatory fat. The most affected bowel segment at BL was used for all IUS parameters. Correlations/% agreement between IUS response/remission and clinical (CDAI70, clinical response/remission), biomarker (CRP/FCal levels) and endoscopy outcomes (SES-CD scores) were assessed. Results The analysis included 82/94 patients enrolled in the IUS substudy; n = 76 patients had BL and ≥1 post-BL IUS assessment. BL characteristics were similar to those of the main STARDUST population. Overall IUS response and remission (transmural healing) rates at W16 were 33.8% and 11.3%, respectively (Table 1). The most affected segments were ileum in 66% and colon in 34% of patients, with better outcomes found in the colon (Table 2). BWT and Doppler’s signal started to normalise at W8, inflammatory fat and echo stratification at W16 (Table 2). Mean BWT improvement from BL was statistically significant as early as W4 (p = 0.0002; Table 3). Moderate agreement was observed between earlier IUS responses and later biomarkers/endoscopic improvements. Conclusion This was the first international, interventional, multicentre study using IUS in CD. IUS response to UST was detected as early as Week 4, and a clinically meaningful % of patients achieved transmural healing, primarily in the colon, at W16. IUS could be a valuable tool to detect early response to treatment in CD. Future studies need to confirm whether early IUS response is predictive of long-term outcomes for CD patients.

P129 Value of diffusion-weighted magnetic resonance enterocolonography for assessing Crohn’s disease activity

Abstract Background We aimed to determine diffusion-weighted imaging (DWI) value to predict active Crohn’s disease (CD) and compare apparent diffusion coefficients (ADC) with endoscopic and conventional magnetic resonance imaging (MRI) CD activity indices. Methods Overall, 229 patients with suspected CD prospectively underwent magnetic resonance enterocolonography (MR-EC) with DWI sequence and ileocolonoscopy. Magnetic resonance activity index (MaRIA), Clermont index, and CD endoscopic index of severity (CDEIS) were calculated. Results Out of 229 investigated patients, the clinical diagnosis of CD was confirmed in 100 persons. Using receiver operating characteristic curve, we showed that DWI score ≥2 had 96.9% sensitivity and 82.3% specificity for diagnosing CD. A threshold of ADC value of 1.30×10–3mm2/s can distinguish between normal and inflamed bowel segments with a sensitivity of 73.8% and a specificity of 98% using Copenhagen diagnostic criteria as the reference standard. While using MaRIA, the threshold of ADC value was established of 1.32 × 10–3 mm2/s with sensitivity and specificity (97.9%, 97.8%). ADC correlated with MaRIA-G (global) (r = -0.69, p = 0.001), Clermont-G (r = -0.722, p = 0.001) and CDEIS (r = -0.69, p = 0.001). Conclusion DWI is a valuable tool which is able to identify inflamed bowel segments as accurate as conventional MARIA score and to discriminate between mild and moderate and severe CD activity.

Sarcopenia and visceral obesity assessed by computed tomography are associated with adverse outcomes in patients with Crohn's disease.

Altered body composition may impact on the clinical course of Crohn's disease (CD) but is not detected by the simple body mass index (BMI) assessment. To assess the prevalence of sarcopenia and visceral obesity by a single computed tomography (CT) slice, and its association with adverse events in an adult hospitalized CD cohort. 88 CD patients who had abdominal CT scans during hospitalization were retrospectively enrolled. The skeletal muscle index (SMI) at the third lumbar vertebra level was used to assess sarcopenia. Sarcopenia was defined as a SMI <38.5cm2/m2 in women, <52.4cm2/m2 in men and visceral obesity as a visceral fat area ≥130cm2. Clinical malnutrition was defined by a BMI <18.5kg/m2. Univariate analysis was performed, and predictors for surgery in the follow-up were entered in a stepwise logistic regression model for multivariate analysis. The prevalence of sarcopenia was 58%, malnutrition 21.6%, and visceral obesity 19.3%. Among sarcopenic patients, 49% had a normal BMI, 13.7% were overweight, and 1(2%) was obese. Sarcopenic CD patients had significantly more abscesses (51% vs 16.7%, p=0.001), hospitalizations (61.2% vs 36.1%, p=0.022) and digestive surgery (63.3% vs 27.8%, p=0.001) than non-sarcopenic patients during the follow-up, whereas usual malnutrition assessment was not correlated with disease outcomes. In multivariate analysis, both sarcopenia and visceral obesity were associated with further occurrence of digestive surgery. Both sarcopenia and visceral obesity were associated with adverse outcomes in severe CD patients whereas usual nutritional assessment was not.

Use of Vitamin D With Anti-Tumor Necrosis Factor Therapy for Crohn's Disease.

BackgroundVitamin D (VD) has an important role in regulating gut mucosal immunity, and seems to be inversely linked to disease activity and more frequent relapses in inflammatory bowel disease. In this study, we evaluated patients with Crohn’s disease (CD) treated with anti-tumor necrosis factor (TNF) in association with VD.MethodsA double-blind, randomized, prospective study was conducted. Thirty patients with a history of moderate to severe CD, in use of anti-TNF, of both sexes, 18 to 70 years, with the dosage of VD < 75 nmol/L (30 ng/mL) were randomized and divided into three groups: group 1 (G1): 10 patients received 2,000 IU VD, per os (PO)/week for 8 weeks; group 2 (G2): 10 patients received 10,000 IU VD, PO/week for 8 weeks; group 3 (G3): 10 patients received 50,000 IU VD, PO/week for 8 weeks. Before and at the end of 8 weeks patients were submitted to VD, fecal calprotectin (FC) and C-reactive protein (CRP) dosage. Follow-up period was 52 weeks, and they are checked for disease activity recurrence (Crohn’s disease activity index (CDAI) > 150, FC > 300 and computerized tomography (CT) scan), FC, CRP, and VD levels.ResultsIncreased VD levels were observed in all groups (P < 0.0001). CRP did not change. There was a significant decrease of FC in G3 (1,014 ± 850 vs. 483 ± 564; P = 0.04), no significant decrease in G2 (76,767 ± 751 vs. 535 ± 823; P = 0.2) and increase in G1 (1,101 ± 744 vs. 1,357 ± 819; P = 0.4). During the 52-week follow-up period, it was showed that recurrent disease activity (CDAI > 150, FC > 200 and CT scan) was predominant in patients with VD < 30 group, and the remission rate was predominant in patients with VD > 30 group (P = 0.0001). A statistically significant difference in VD levels was noted in CD patients after 52 weeks that presented flare or disease remission (P = 0.001).ConclusionsUse of VD associated with anti-TNF treatment may improve clinical response in CD. VD levels greater than 30 ng/mL have better rates of remission.

Anti-IL-12/23p40 antibodies for maintenance of remission in Crohn's disease.

Anti-IL-12/23p40 antibodies for maintenance of remission in Crohn's disease.

Combination Therapy of Adalimumab With an Immunomodulator Is Not More Effective Than Adalimumab Monotherapy in Children With Crohn's Disease: A Post Hoc Analysis of the PAILOT Randomized Controlled Trial.

The PAILOT trial was a randomized controlled trial aimed to evaluate proactive vs reactive therapeutic drug monitoring in children with Crohn's disease (CD) treated with adalimumab. Our aim in this post hoc analysis of the PAILOT trial was to assess the efficacy and safety of adalimumab combination treatment in comparison with monotherapy at week 72 after adalimumab induction. Participants were children 6-17 years old, biologic naïve, with moderate to severe CD, who responded to adalimumab induction at week 4. Patients receiving immunomodulators at baseline maintained a stable dose until week 24; patients could then discontinue immunomodulators. At each visit, patients were assessed for disease index, serum biomarkers, fecal calprotectin, adalimumab trough concentration, and anti-adalimumab antibodies. Out of the 78 patients (29% female; mean age, 14.3 ± 2.6 years), 34 patients (44%) received combination therapy. During the study period, there was no significant difference in the rates of sustained corticosteroid-free clinical remission (25/34, 73%, vs 28/44, 63%; P = 0.35) or sustained composite outcome of clinical remission, C-reactive protein ≤0.5 mg/dL, and calprotectin ≤150 µg/g (10/34, 29%, vs 14/44, 32%; P = 0.77) between the combination group and the monotherapy group, respectively. Clinical and biological outcomes did not differ between the proactive and reactive subgroups within the combination and monotherapy groups. Adalimumab trough concentrations and immunogenicity were not significantly different between groups. The rate of serious adverse events was not significantly different between groups but was numerically higher in the monotherapy group. Combination therapy of adalimumab and an immunomodulator was not more effective than adalimumab monotherapy in children with CD (ClinicalTrials.gov No. NCT02256462).

Development and Validation of a Test to Monitor Endoscopic Activity in Patients With Crohn’s Disease Based on Serum Levels of Proteins

Noninvasive tests to measure endoscopic activity in patients with Crohn's disease (CD) have limitations. We aimed to develop a test to identify patients in remission, based on endoscopic analysis, and monitor CD activity based on serum levels of proteins. We developed a test to measure 13 proteins in blood (ANG1, ANG2, CRP, SAA1, IL7, EMMPRIN, MMP1, MMP2, MMP3, MMP9, TGFA, CEACAM1, and VCAM1), called the endoscopic healing index [EHI], using samples from 278 patients with CD from a multinational training cohort. We validated the test using 2 independent cohorts of patients with CD: 116 biologic-naive patients with early-stage CD (validation cohort 1) and 195 biologic-exposed patients with chronic CD (validation cohort 2). The ability of the test to identify patients with active disease vs patients in remission (defined as a simple endoscopic score for CD of ≤2 and ≤1 in each segment, or a total CD endoscopic index of severity score <3) was assessed by using area under receiver operating characteristic curve (AUROC) analysis. The diagnostic accuracy of the test was compared with that of measurement of serum C-reactive protein (CRP) and fecal calprotectin. The EHI scores range from 0 to 100 units; higher scores indicate more severe CD activity, based on endoscopy findings. The EHI identified patients in remission with an AUROC of 0.962 in validation cohort 1 (95% confidence interval, 0.942-0.982) and an AUROC of 0.693 in validation cohort 2 (95% confidence interval, 0.619-0.767), regardless of CD location or phenotype. A cutoff value of 20 points identified patients in remission with the highest level of sensitivity (97.1% in validation cohort 1 and 83.2% in validation cohort 2), with specificity values of 69.0% and 36.6%, respectively. A cutoff value of 50 points identified patients in remission with the highest level of specificity (100% in validation cohort 1 and 87.8% in validation cohort 2), with sensitivity values of 37.3% and 30.0%, respectively. The EHI identified patients in remission with a significantly higher AUROC value than the test for CRP (0.876, P < .001 in validation cohort 1 and 0.624, P= .109 in validation cohort 2). In analysis of patients with available FC measurements, the AUROC value for the EHI did not differ significantly from that of measurement of FC (AUROC, 0.950 for EHI vs AUROC, 0.923 for FC; P= .147 in validation cohort 1 and AUROC, 0.803 for EHI vs AUROC, 0.854 for FC; P= .298 in validation cohort 2). We developed an index called the EHI to identify patients with CD in endoscopic remission based on blood levels of 13 proteins. The EHI identified patients with resolution of endoscopic disease activity, with good overall accuracy, although with variation between the 2 cohorts assessed. The EHI AUROC values were comparable to measurement of FC and higher than measurement of serum CRP. The test might be used in practice to assess endoscopic activity in patients with CD.

Positioning Therapies in the Management of Crohn’s Disease

In the past decade, several new therapies with different mechanisms of action have been approved for the management of moderate to severe Crohn's disease. However, there is limited guidance on optimal positioning of agents as first- or second-line therapies because of the absence of head-to-head trials. Furthermore, given the lack of comparative studies, treatment guidelines have provided limited insight. In this review, we discuss data on key treatment attributes, comparative efficacy and safety, factors predictive of response to each agent, and propose an algorithm for positioning therapies for the management of patients with low-risk and high-risk Crohn's disease.

3151 Ustekinumab Administration Prior to Week Eight Following Induction Improves Symptoms and Maintains Remission of Severe Crohn's Disease: A Case Series

INTRODUCTION: Ustekinumab is a recently approved immunosuppressive agent for management of moderate to severe Crohn's Disease (CD). In trials, dosing was determined at 6 mg/kg for induction with maintenance injection of 90 mg every 8 weeks. Approximately half of the patients in the UNITI Induction trials did not respond to ustekinumab treatment when assessed at 6-8 weeks, and were included in the Maintenance trial with ustekinumab provided at week 8 or 12. Only 30-40% of these patients continued to have remission at maintenance trial conclusion. We present a case series of two CD patients who were initiated on ustekinumab therapy but required a shortened maintenance dose interval to achieve/maintain remission. CASE DESCRIPTION/METHODS: Case 1: A 33 year old female presenting clinically with intermittent abdominal pain, diarrhea, occasional blood in stool &amp; nocturnal symptoms was diagnosed with CD in 2017 via computed tomography of the abdomen combined with colonoscopy revealing terminal ileum aphthous ulceration. Previous therapies included budesonide, prednisone &amp; adalimumab. Ustekinumab induction was initiated on 2/2/2018. However, on 3/20/2018, the patient developed severe abdominal pain consistent with a CD flare. Following, she has received ustekinumab injections every 4-6 weeks to maintain disease remission. Case 2: A 47 year old male initially diagnosed with CD at the age of 22, complicated by emergent colectomy with end ileostomy in 2014 presented with an acute flare consisting of abdominal pain, peristomal fistulas and increased ostomy output. Following evaluation, he underwent surgical correction of fistula, drainage of intraabdominal wall abscess &amp; abdominal wall reconstruction in December 2018. Prior to this, he was treated with sulfasalazine, mercaptopurine, azathioprine along with immunomodulators including infliximab &amp; certolizumab without adequate response. In January 2019, ustekinumab therapy was initiated with standard induction followed by injectable dosing every 4 weeks due to CD severity and physician recommendation. Following this schedule, the patient has had improved ostomy output and symptom control. DISCUSSION: In our experience, shortening the interval of injectable ustekinumab dosing to 4-6 weekly from 8 weeks has proven successful in maintaining remission for patients with severe CD. This subsegment of CD patients was excluded in trials and further investigation is needed to assess long term efficacy of shortened ustekinumab therapy intervals to maintain remission.

796 Effect of Disease Location on Endoscopic and Radiographic Outcomes in Patients With Moderate to Severe Crohn's Disease Initiated on Vedolizumab

INTRODUCTION: Vedolizumab (VDZ), an integrin antagonist, is approved to treat moderate to severe Crohn's disease (CD). We aimed to investigate how CD location effected the endoscopic and radiographic outcomes of VDZ. METHODS: This is a retrospective study from a tertiary care center, in patients (pts) with CD initiated on VDZ between July 2014 and January 2018. Pts had endoscopic or radiographic evaluation before (index examination) and &gt;3 months after (follow-up examination) VZD initiation. Endoscopic remission/response was defined as resolution (remission) or significant improvement (response) of CD features with respect to the index examination. Endoscopic remission/response rate was compared between ileal and colonic disease. Improvement in radiographic features of small bowel (jejunum/ileum) CD was evaluated on magnetic resonance imaging or computed tomography scan. RESULTS: 140 pts were evaluated with a median follow-up 18 months (range: 3-55) (Table 1). 90% of the pts (n = 126) had prior anti-TNFα failure. 128 pts had endoscopic evaluation with a median follow up 27 months (3-55) (Table 2). Endoscopic remission/response rates between pts with ileal CD (62% [47/76]) and pts with colonic CD (49% [34/69]) were not statistically different (P = 0.13). Endoscopic remission/response rates in pts with isolated ileal CD (n = 59) and isolated colonic CD (n = 52) were similar (59% vs. 46% respectively; P = 0.17). Among pts with both ileal and colonic disease (n = 17), endoscopic remission/response rates were similar in ileal and colonic CD (71% vs. 59% respectively; P = 0.47). Endoscopic remission/response rate in the ileal disease in pts with prior ileocolic resection (ICR; n = 38) was lower than in pts with an intact anatomy (n = 22) (55.3% vs. 77.3% respectively; P = 0.05). Follow-up imaging was available in 30 pts with radiographic evidence of small bowel CD (median follow up 13 months [3-28]). Radiographic improvement was observed in 26.7% of pts. CONCLUSION: In this cohort of pts with CD, majority anti-TNF experienced, a significant number of pts had improvement in endoscopic features of CD on VDZ, regardless of CD location. Ileal disease in pts with prior ICR appears to be less responsive to VDZ as compared to in pts with an intact anatomy. Radiographic features of small bowel CD showed a low rate of improvement on VDZ. Further understanding of the impact of VDZ on small bowel CD is warranted.

2169 Endoscopic Stricturotomy via Argon Plasma Coagulation With Balloon Dilation for Refractory Colonic Stricture Secondary to Crohn’s Disease

INTRODUCTION: Stricture is a significant complication in patients with Crohn’s disease (CD). Up to 80 % of patients will require at least one surgery for stricture, fistula, or abscess during their lifetime. The current treatment modalities are surgery, endoscopic balloon dilation (EBD), or endoscopic stricturotomy (ES) via a needle-knife or electrosurgical knife. We report a combined endoscopic stricturotomy via argon plasma coagulation (APC) with balloon dilation in a patient with refractory benign colonic stricture due to Crohn disease. CASE DESCRIPTION/METHODS: A 56-year old man with a twenty-seven-year history of Crohn’s disease presented to the clinic with chronic right-sided abdominal pain. He has two to three bowel movements a day. He is a non-smoker, denied alcohol, or illicit drug use. He had prior use of anti-TNF inhibitor with secondary loss of response. Current medication included azathioprine, esomeprazole, and ustekinumab injection every eight weeks. Vital signs were normal. The abdomen was soft, non-tender, no organomegaly, normal bowel sounds, and normal rectal exam. Labs revealed hemoglobin 14.2 g/dl, leukocyte count 7k/mm3, platelets 393k/mm3, urea nitrogen 13 mg/dl, creatinine 1.0 mg/dl, CRP 0.9, mg/dl and fecal calprotectin 59 ug/g. Magnetic resonance enterography (MRE) was performed and revealed severe short segment stricture of the mid ascending colon (Figure 1). He underwent a colonoscopy, and it showed a benign-appearing, severe non-traversed stricture measuring 3 cm in length x 1.1 cm in inner diameter in the ascending colon (Figure 2). Coagulation for tissue destruction and stricturotomy using pulsed argon plasma at 1.5 liters/minute and 40 watts was accomplished, followed by balloon dilator up to 15 mm with significant improvement in the luminal narrowing (Figure 3). The site was traversed, and the cecum was inspected. The patient was seen in the clinic two months later, and he was doing well, and his abdominal pain was resolved. DISCUSSION: Surgery is still considered to be the standard therapy in patients with a colonic stricture. Endoscopic stricturotomy has emerged as a promising modality to avoid or minimize the need for surgery. Up to our knowledge, using the APC mediated ES has not been reported. So, we report the successful use of this technique combined with balloon dilation in a patient with severe CD- associated benign stricture. The clinician should be aware of such procedure as an effective treatment modality in refractory benign colonic stricture.

777 Effect of Ustekinumab Dose Escalation on Recapturing Clinical Response in Patients With Crohn's Disease

INTRODUCTION: Previous studies have shown that ustekinumab (UST) is an effective induction and maintenance therapy for patients with moderate to severe Crohn's Disease (CD). We sought to examine the real-world efficacy and safety of UST and whether UST dose escalation helps to recapture clinical response. METHODS: All patients who received the initial weight-based UST infusion between 4/2017 and 4/2018 were identified through a query of the EMR. Patients were followed from the time they initiated UST through 5/2019 or their date of UST discontinuation, whichever came first. Specifically, patients who lost response to UST 90 mg injection every 8 wk dosing and were then dose escalated to either every 4 or 6 wk dosing were identified. Recaptured clinical response to dose escalation was determined by reviewing clinical documentation and assessing for a reduction of ≥3 in the modified Harvey Bradshaw index (mHBI) after ≥8 wks following dose escalation. RESULTS: We included 27 patients with CD [median age 40 (range 24-61); 56% male; 96% tumor necrosis factor (TNF)-antagonist exposed]. Table 1 compares characteristics and outcomes of patients who underwent dose escalation vs. those who remained on regular dosing. Of the 11 dose escalated patients, 9 were switched to an every 4 wk regimen while the other 2 were switched to an every 6 wk regimen. Patients who underwent dose escalation were more likely to be a smoker (18% vs. 13%), have a history of perianal disease (73% vs. 38%), have previously tried a greater number of biologics (2.7 vs. 1.9), and be exposed to concomitant steroid (55% vs. 25%). Moreover, patients who underwent dose escalation were less likely to achieve steroid discontinuation within the first 8 wks compared to those who remained on regular dosing (9% vs. 50%). The only adverse event in the dose escalation group was one case of pneumonia. Table 2 further examines those patients that underwent dose escalation. The median mHBI improved from 9 to 7 following dose escalation. Recaptured clinical response occurred at a rate of 6/11 (55%) based on clinical documentation and 3/11 (27%) based on mHBI. CONCLUSION: UST dose escalation from 90 mg every 8 wks to either every 4 or 6 wk dosing allowed for recaptured clinical response in ∼25-50% of CD patients. There were minimal adverse events in patients who were dose escalated. Given its safety profile, dose escalation should be considered in patients with moderate to severe CD who have incomplete response to UST.

690 Ustekinumab Maintained Clinically Meaningful Improvement in Health-Related Quality of Life in Patients With Moderate to Severe Crohn's Disease: Results From the IM-UNITI Long-Term Extension

INTRODUCTION: The IM-UNITI study evaluated the safety and efficacy of subcutaneous (SC) ustekinumab (UST) maintenance therapy in patients with moderately to severely active Crohn's disease (CD) who completed induction treatment with UST. Previously, we reported the effects of UST on health-related quality of life (HRQoL) through Wk44. Here, we evaluated HRQoL through Wk140 in patients who entered the long-term extension of the IM-UNITI study. METHODS: Patients who completed the safety and efficacy evaluation at Wk 44 of the maintenance study were eligible to continue their regimen in the extension study (placebo [PBO], UST 90 mg q12w, or UST 90 mg q8w). All patients who were treated in the extension study were included in this analysis of Inflammatory Bowel Disease Questionnaire (IBDQ) and SF-36 data according to the treatment they received during the extension study. The IBDQ is a 32-item questionnaire with 4 dimensions: bowel symptoms, systemic symptoms, emotional function, and social function. The total score ranges from 32 to 224, higher scores indicate better quality of life, and a change ≥16 points was defined as clinically meaningful. For SF-36, a change ≥5 points was defined as clinically meaningful. RESULTS: For patients who entered the extension, mean total IBDQ scores and SF-36 scores at maintenance baseline were comparable across treatment groups (Table 1). Patients who received UST maintained the improvement in IBDQ and SF-36 that was achieved by maintenance baseline through Wk140, and those who received PBO generally worsened. Through Wk 140, 26.5% of patients receiving PBO, 61.5% of patients receiving UST 90 mg q12w, and 59.3% of patients receiving UST 90 mg q8w had ≥16-point improvements from induction baseline in IBDQ score. In addition, 10.9%, 51.6%, and 54.2%, respectively, had ≥5-point improvements in SF-36 physical component summary scores, and 8.7%, 43.8%, and 43.7%, respectively, had ≥5-point improvements in SF-36 mental component summary scores during the same period. CONCLUSION: In patients who entered the long-term extension of the IM-UNITI study, those who received SC UST maintenance generally maintained improvements in IBDQ and SF-36 scores that were achieved through IV induction, and those who received PBO gradually lost these improvements.

735 Crohn's Disease Patients Who Do Not Qualify for Clinical Trials Have Similar Clinical and Endoscopic Response Rates to Ustekinumab to Those Who Qualify for Clinical Trials

INTRODUCTION: The UNITI clinical trial demonstrated ustekinumab (UST) safety and efficacy for moderate to severe Crohn's disease (CD) patients. However, exclusion criteria preclude enrollment of complex patients impacting external validity of the findings. The aim of this study was to evaluate UST response in active CD patients who would not have qualified for the randomized controlled trials (RCTs). METHODS: A retrospective cohort study of UST-treated CD patients who would not qualify (DNQ) and who would qualify (Q) for RCTs from 2016 to 2018 was performed. Inclusion criteria included symptomatic luminal CD activity (defined as abdominal pain and stool frequency), induction with UST infusion at CD dosing and ≥1 clinic visit post-induction. Criteria for DNQ patients were extracted from the published UNITI study protocol. The primary outcome of interest was week 8 clinical response rates (&gt;50% improvement in abdominal pain and stool frequency from baseline) between Q vs DNQ groups. Secondary outcomes were endoscopic response, corticosteroid free clinical remission, dose escalation and adverse events between the two groups. RESULTS: 201 patients (Q = 111; DNQ = 90) with a median 6 months follow up (IQR 4-9 months) were included. The DNQ cohort had lower hemoglobin levels, more active perianal disease, upper tract disease, ileocolonic disease, and prior surgeries (Table 1). Week 8 clinical response rates were similar between Q and DNQ (64.0% vs 60.0%; P = 0.56). Clinical response, remission and steroid-free remission rates during maintenance were also similar between the two groups (Table 2). However, more patients in the DNQ group required dose escalation (64.4%) compared to the Q group (46.8%), P = 0.01, especially after induction dosing. Endoscopic response rates were similar between Q and DNQ groups, with complete mucosal healing achieved in 13.2% vs 13.6% of Q and DNQ patients (P = 0.94) (Table 2). CONCLUSION: These findings suggest that ustekinumab is equally efficacious for complex CD patients who would not have qualified for RCTs. Adverse events were infrequent for all UST treated patients. The majority of DNQ patients required dose escalation during their treatment course, suggesting more intensive therapy may be warranted for this patient subgroup. Further studies are needed to determine durable clinical and endoscopic response from dose escalation in this complex CD group.

656 Ustekinumab Dose Escalation Is Effective in Treatment of Crohn's Disease

INTRODUCTION: Ustekinumab (UST) is approved for moderate to severe Crohn's disease (CD) at 90 mg every 8 week dose for maintenance. However, there is limited data about the benefit of UST dose escalation. The aim of this study was to evaluate the response to UST dose escalation in a real-world cohort of active CD patients. METHODS: CD patients who had partial or no clinical response to standard UST induction and/or maintenance and required dose escalation to 90 mg every 4 or 6 weeks from 2016 to 2018 at a tertiary IBD referral center were retrospectively identified. Patients who did not receive UST intravenous induction dose or had clinically inactive disease at the time of dose escalation were excluded. Response and remission were defined based on physician global assessment. Primary outcome was clinical response to dose escalation. Secondary outcomes were clinical remission and endoscopic response to dose escalation. Multivariable regression with backward elimination was performed to identify predictors of clinical response to UST dose escalation. RESULTS: A total of 68 patients received UST dose escalation, median age of the cohort was 39 years, 56% of patients were females. The majority (51.5%) had ileocolonic disease. 57.4% had stricturing disease, and 39.7% had non-stricturing non-penetrating disease. 54.4% had a prior surgical resection. Prior medication exposure included: immunomodulators (78%), anti-TNF (95.3%) and anti-integrin drugs (46.9%). Overall, 67.8% of patients had clinical response at week 8 after UST induction dose. Following UST dose escalation, 79.4% of patients had a clinical response and 30.9% achieved clinical remission within 3-6 months. Of the patients with available endoscopic follow-up data (n = 39), 59% had endoscopic response, and 20.5% achieved endoscopic remission. Baseline characteristics between responders and non-responders to UST dose escalation were similar except for a higher proportion of responders having had clinical response to UST induction dose (Table 1). On multivariable regression analysis, response to UST induction therapy was the only independent predictor of response to UST dose escalation (OR 7.01; 95% CI 1.83-27.07; P = 0.005). CONCLUSION: A majority of patients with moderate to severe CD benefited from UST dose escalation suggesting the clinical utility of optimizing dosing in the treatment course. Response to UST induction dose may be a strong predictor of subsequent response to UST dose escalation.

2107 A Case of Crohn’s Disease Complicated With Liver Abscess, Enterohepatic and Enterocutaneous Fistulas

INTRODUCTION: Crohn’s disease (CD) is a chronic inflammatory disease which can affect any part of the gastrointestinal tract. Liver abscesses and fistulas between a solid organ and intestine are rare. Here we present a unique case report of a CD patient who developed liver abscesses complicated by enterohepatic and enterocutaneous fistula. CASE DESCRIPTION/METHODS: 48-year-old male with a longstanding history of CD presented with abdominal pain. A CT of the abdomen revealed multifocal hepatic abscesses (Figure 1). The abscesses were initially percutaneously drained and antibiotics were administered. Five weeks following discharge he presented with complains of worsened abdominal pain. He had developed a foul smelling pus-draining wound at site of the drainage. A repeated CT abdomen revealed persistent hepatic abscess with small bubbles of free air adjacent to the inferior hepatic edge with a thin enhancing tract suggesting an early enterohepatic fistula (Figure 2) and an enterocutaneous fistula in the lateral abdominal wall between the bowel and the skin (Figure 3). He underwent a right hemicolectomy with drainage of the hepatic abscesses and repair of the enterocutaneous and enterohepatic fistula. The biopsies from the ileo-cecal region showed extensive ulceration with underling transmural inflammation of mucosa and extensive active inflammation of visceral serosa with reactive fibrosis, suggestive of severe CD. His postoperative recovery was uneventful. Routine colonoscopy evaluation of the ileo-colonic anastomosis two months later showed erythema and inflammation at the anastomosis site with granular inflammation throughout the colon (Figure 4). He is currently doing well on Infliximab and has not reported further complications. DISCUSSION: Liver abscess and solid organ to intestinal fistulas are rare complications of CD. The incidence of liver abscess is higher in patients with CD compared with the general population. The diagnosis of liver abscesses is frequently delayed as patients present similar to a CD exacerbation. Unlike the patient in this report, intestinal symptoms may be absent leaving little to no evidence to suggest the presence of a liver abscess on clinical presentation. Imaging including CT scans and ultrasound help to facilitate the diagnosis of this rare condition. In this case, we have shown that surgical intervention, antibiotics and immunotherapy can help with successful outcomes in cases of liver abscesses, enterohepatic and enterocutaneous fistulas.

The Cost-effectiveness of Initial Immunomodulators or Infliximab Using Modern Optimization Strategies for Crohn's Disease in the Biosimilar Era.

Treatment cost, efficacy, and safety are integral considerations when optimizing management of Crohn's disease (CD). This study assessed the cost-effectiveness of initial immunomodulator and anti-tumor necrosis factor (anti-TNF) agents for the treatment of CD from a US third-party perspective, incorporating current treatment algorithms, optimization strategies, and reduced costs availed by biosimilars. A 1-year Markov model was developed to simulate the cost and quality-adjusted life-years (QALYs) of initial azathioprine, infliximab, and combination therapy for moderate to severe CD. Treatment was changed based on tolerability and clinical disease activity at 3-monthly intervals. Efficacy data were based on published literature. Initial azathioprine had the lowest cost and utility ($35,337 and 0.63 QALYs), whereas combination therapy was the costliest yet conferred the highest health benefits ($57,638 and 0.67 QALYs). The incremental cost-effectiveness of infliximab and combination therapy compared with azathioprine were both in excess of $500,000 per QALY gained. Initial azathioprine remained the most cost-effective treatment on sensitivity analysis compared with infliximab and combination therapy, with 90% reductions in anti-TNF therapy costs and a 5-year time horizon, although combination therapy had an acceptable cost-effectiveness when costs were reduced in the extended model. Initial infliximab, ustekinumab, and vedolizumab were dominated by combination therapy. In the biosimilar era, initial azathioprine with escalation to infliximab appeared more cost-effective in the short term compared with infliximab or combination therapy, although initial combination therapy yields acceptable ICERs in the long term with continued reductions in anti-TNF therapy costs and will likely be the preferred treatment strategy in the future.

Certolizumab pegol for induction of remission in Crohn's disease.

Crohn's disease (CD) is a chronic inflammatory disease of the gastrointestinal tract, and immune response modulation is the main treatment strategy to induce remission in active CD. Certolizumab pegol (CZP) is a tumor necrosis factor-alfa (TNF-α) inhibitor which regulates impaired immune response. The primary objectives were to evaluate the efficacy and safety of CZP for the induction of remission in CD. We searched MEDLINE, Embase, CENTRAL, the Cochrane IBD group specialized register, trials registers and other sources from inception to 28 January 2019. Moreover, we contacted the pharmaceutical company that manufactures CZP. We included randomized controlled trials comparing CZP with placebo or no treatment in active CD patients. We used standard Cochrane methodological procedures. The main outcomes selected for GRADE analysis were clinical remission at week 8 (Crohn's Disease Activity Index [CDAI] ≤150), clinical response at week 8 (CDAI reduction ≥ 100 or clinical remission), and serious adverse events. The Mantel-Haenszel random-effects method was applied for the statistical analyses. For dichotomous outcomes, we calculated the risk ratio (RR) and corresponding 95% confidence interval (95% CI). Four studies involving 1485 participants with moderate to severe CD met the inclusion criteria and were used in the meta-analyses. All studies included active CD patients with CDAI ranging from 220 to 450. Most patients were adults over 18 years of age. One study was identified as high risk of bias due to a non-identical placebo while the other studies were judged to be at low risk of bias.CZP (100 mg to 400 mg every 2 to 4 weeks) was shown to be superior to placebo for achieving clinical remission at week 8 (RR 1.36, 95% CI 1.11 to 1.66; moderate certainty evidence). The raw numbers of participants achieving clinical remission at week 8 were 26.9% (225/835) and 19.8% (129/650) in the CZP and the placebo groups, respectively.CZP was shown to be superior to placebo for achieving clinical response at week 8 (RR 1.29, 95% CI 1.09 to 1.53; moderate certainty evidence). In raw numbers, clinical response at week 8 was achieved in 40.2% (336/835) and 30.9% (201/650) of participants in the CZP and the placebo groups, respectively.In raw numbers, serious adverse events were observed in 8.7% (73/835) and 6.2% (40/650) of participants in the CZP and the placebo groups, respectively (RR 1.35, 95% CI 0.93 to 1.97; moderate certainty evidence). Serious adverse events included worsening Crohn's disease, infections, and malignancy. Moderate certainty evidence suggests that CZP is effective for induction of clinical remission and clinical response in participants with active CD patients. It is uncertain whether the risk of serious adverse events differs between CZP and placebo as the 95% CI includes the possibility of a small decrease or doubling of events. Future studies are needed to evaluate the long-term efficacy and safety of CZP in CD patients.