Tertiary Inflammatory Bowel Disease Center Research Articles

Sequential Use of High-Dose Tofacitinib After Infliximab Salvage Therapy in Acute Severe Ulcerative Colitis.

Preliminary data regarding the effectiveness of tofacitinib in acute severe ulcerative colitis [ASUC] have been presented in two previous case series. We aimed to describe the novel use of high-dose tofacitinib immediately following non-response to infliximab in the setting of steroid-refractory ASUC. Five patients who received high-dose tofacitinib 10 mg three times a day immediately following non-response to infliximab for steroid-refractory ASUC were identified at an Australian tertiary inflammatory bowel disease centre. Four of the five patients demonstrated clinical response to high-dose tofacitinib induction during their inpatient admission, with one patient requiring colectomy owing to a lack of clinical response. At 90 days, all four initial responders remained colectomy-free, with two patients achieving combined clinical and endoscopic remission. No adverse events directly attributable to high-dose tofacitinib were identified. High-dose tofacitinib may have a role as salvage therapy in the setting of steroid-refractory ASUC. Prospective studies are required to determine the safety and efficacy of high-dose tofacitinib to determine whether it can be routinely recommended as primary or sequential salvage therapy in the setting of steroid-refractory ASUC.

P415 Paradoxical onset of Takayasu’s arteritis in patients with inflammatory bowel disease treated with anti-tumour necrosis factor-α agents

Abstract Background Takayasu’s arteritis (TA) is a rare complication associated with inflammatory bowel disease (IBD). TA is a granulomatous systemic vasculitis of uncertain aetiology affecting large arteries, predominantly the aorta and its main branches, leading to stenotic and expansible lesions. The estimated prevalence of coexisting of TA in patients with ulcerative colitis (UC) is 0.3%, and that in patients with Crohn’s disease (CD) is 0.1%. Anti-tumour necrosis factor-α (TNF-α) agents are used to treat both TA and IBD, although some patients with IBD paradoxically develop TA during treatment with anti-TNF-α agents. However, data regarding the incidence and clinical features of TA in such cases are lacking. This study was performed to clarify the prevalence, risk factors, and clinical features of TA that develops paradoxically during treatment with anti-TNF-α agents in patients with IBD. Methods Consecutive patients with IBD who were regularly seen at our centre, a tertiary IBD centre in Japan, from 2000 to 2019 were included in this retrospective single-centre study. We evaluated the prevalence of TA according to the presence or absence of treatment with anti-TNF-α agents and the patients’ clinical manifestations. Results Of 1846 patients with UC and 1249 patients with CD, 7 (0.23%) patients with UC developed TA. The prevalence of TA in patients treated with anti-TNF-α agents was significantly higher (4/254, 1.6%) than that in patients without anti-TNF-α agent treatment (3/1592, 0.19%) (p=0.0087, Fisher’s exact test). Among four patients with UC who paradoxically developed TA during treatment with anti-TNF-α agents, three (75%) received infliximab, one (25%) received adalimumab, and one (25%) received golimumab. One was male and three (75%) were female. The median interval from starting treatment with anti-TNF-α agents to diagnosis of TA was 49.0 (34–63) months. All patients had pancolitis as well as persistent active colitis resistant to anti-TNF-α antibody treatment. The treatments for TA administered after anti-TNF-α therapy were as follows: Two (50%) patients discontinued anti-TNF-α agent therapy, three (75%) were treated with prednisolone, and one (25%) received tocilizumab. No patient required an operation for TA. Conclusion To our knowledge, this is the first study to show the prevalence and clinical features of TA in patients with IBD following administration of anti-TNF-α agent therapy. Although TA is a rare complication, our results suggest that it can develop as paradoxical reaction following administration of anti-TNF-α agents.

P470 Ustekinumab Trough Levels are not Associated with Clinical Response in Inflammatory Bowel Disease Patients

Abstract Background Ustekinumab (UST) has been shown to effectively induce and maintain remission in inflammatory bowel disease (IBD). Only a few studies thus far have focused on UST pharmacokinetics suggesting that both, trough levels after i.v. induction as well as trough levels during stable maintenance might be associated with clinical and endoscopic response to UST. Data from real-world cohorts in this setting are scarce. Therefore, the aim of our study was to assess whether clinical response to UST was associated with a specific pharmacokinetic pattern. Methods All IBD patients treated with UST in one tertiary IBD centre between January 2017 and August 2020 were retrospectively retrieved from the database. Disease activity was assessed by Harvey-Bradshaw index (HBI) and partial Mayo score in Crohn’s disease (CD) and ulcerative colitis (UC) pts; respectively. Clinical response was defined as a decrease of HBI of ≥2 points or partial Mayo score ≥3 points. Patients not responding to therapy by week 16, or loosing original response received dose escalation from 90mg s.c. every 8 weeks to 90mg every 4 weeks. UST through levels were assessed by commercially available ELISA kit (IDKmonitor®) at week 8 after i.v. induction and/or during maintenance therapy after a minimum period of 16 weeks of treatment. Results In total, 61 IBD patients were included (mean age 38 years, range 22–70; 38 women; 54 CD/6 UC/1 IBD-U). All patients were antiTNF experienced, minority (11; 18%) had also been treated with vedolizumab prior UST. Thirty-nine pts (64%) were responders, out of these 15 pts (38%) required dose escalation at some point of the treatment due to secondary loss of response. UST through levels at week 8 were significantly higher than the maintenance levels (mean 5.6±SEM 0.7µg/mL vs. 2.2±0.3µg/mL; p<0.001). There were no significant differences between responders and non-responders neither in trough levels after induction (5±0.8µg/mL vs. 6.4±1.1µg/mL, p=n.s.), nor in trough levels during maintenance therapy (2.3± 0.4µg/mL vs. 1.9 ±0.4µg/mL, p=n.s.). Patients requiring dose escalation did not differ from stable responders in maintenance trough levels (2.4±0,6 µg/mL vs. 2,3 ±0,4 µg/mL). Conclusion In this limited size real-world cohort of IBD patients, we found no difference in pharmacokinetics between reponders and non-reponders to ustekinumab.

P461 Vedolizumab Dose Escalation in a Real-World Cohort of IBD Patients

Abstract Background Vedolizumab (VDZ) effectively induces and maintains remission in inflammatory bowel disease (IBD). The loss of response to VDZ has been shown to be recaptured with dose escalation but the data in this field are still scarce. In addition, data on pharmacokinetics (PK) of dose escalation are limited and it is unclear whether PK should used in decision-making algorithm in adjusting VDZ dose regimen. Therefore, the aim of our study was to assess clinical efficacy and pharmacokinetic profile of VDZ dose escalation. Methods All IBD patients treated with VDZ in one tertiary IBD centre were retrospectively retrieved from the database. According to local protocol, non-responders to standard dosing of 300 mg i.v. of VDZ every 8 weeks, received escalated dose of 300mg i.v. every 6 or 4 weeks. Disease activity was assessed by Harvey-Bradshaw index (HBI) and partial Mayo score in Crohn’s disease (CD) and ulcerative colitis (UC) pts; respectively. VDZ dose was escalated in case of clinically assessed primary non response by week 22 of the treatment or in case of secondary loss of response. Response to dose escalation was defined as a decrease of HBI of ≥2 points, partial Mayo score ≥3 points or endoscopic improvement. VDZ through levels were assessed at the completion of induction and in dose escalated patients after at least two VDZ administrations in shortened interval. Results In total, 75 IBD patients were included (mean age 47 years, range 20–90; 36 men; 35 CD/39UC/1 IBD-U). Fifty two pts (69%) were primary responders, out of these 23 pts (44%) required dose escalation at some point of the treatment due to secondary loss of response. Out of 23 primary non-responders, 10 stopped the treatment, the remaining 13 received escalated dose of VDZ. Altogether, dose escalation was used in 36 pts (48%). There were no differences in the proportion of CD and UC between conventional and escalated dose regimen groups. Among secondary loss of response, the response was recaptured in 15 out of 23 pts (65%} while only two out of thirteen primary non-responders responded to dose escalation. There were no significant differences in VDZ levels between pts requiring dose escalation and pts with stable response to conventional regimen (mean levels 9,97±1,276 vs. 12,79±1,771 µg/mL; p=n.s.). VDZ levels increased significantly in patients who responded to dose escalation (from 10,12±3,460 to 20,81±3,326 µg/mL; p=0.0497). Conclusion Response to vedolizumab can be successfully recaptured in two thirds of secondary non responders by dose escalation. Patients requiring dose escalation do not seem to differ from stable responders with regards to vedolizumab pharmacokinetics.

P361 No increased postoperative risk of venous thromboembolism in patients with Ulcerative Colitis undergoing colectomy after tofacitinib exposure

Abstract Background Colectomy for ulcerative colitis (UC) has been associated with postoperative morbidity and mortality, including venous thromboembolism (VTE). Patients with inflammatory bowel diseases (IBD) have a 2 to 4-fold increased risk for developing VTE, as compared to non-IBD patients. Due to recent concerns on increased VTE associated with tofacitinib exposure, we aimed to evaluate the 180-day postoperative VTE risk in UC patients undergoing colectomy after tofacitinib use in comparison to patients failing biologicals and undergoing the same surgery. Methods This retrospective cohort study included all UC patients who underwent colectomy between 2014 and 2020 in our tertiary IBD center. All medical charts were reviewed, and clinically relevant information extracted, including indication for colectomy, development of postoperative VTE (deep venous thrombosis, pulmonary or extra-pulmonary embolisms) within 180 days of surgery, low-molecular weight heparin (LMWH) prophylaxis and perioperative therapy exposure (steroids within 1 month prior to surgery, biologicals or tofacitinib within 3 months prior to surgery). Results One-hundred seven UC patients (49.5% women, median [IQR] age 38.0 [27.0 – 53.0] years) underwent colectomy due to refractory disease (n=93), dysplasia or carcinoma (n=12) or polyposis (n=2) (Table 1). Thirty-six (33.6%) patients were operated urgently. At the time of surgery, 44 (41.1%) were on steroids, 38 (35.5%) on anti-TNF agents, 27 (25.2%) on vedolizumab/etrolizumab, 6 (5.6%) on anti-IL12/23 agents and 12 (11.2%) on tofacitinib. All patients received antithrombotic prophylactic LMWH postoperatively. During the 180-day postoperative period, 3 (2.8%) patients developed an intra-abdominal thrombosis, none of them had a history of VTE. Two thromboses were found by coincidence on CT scans which were performed in light of postoperative fever and inflammatory blood tests, the other patient was symptomatic. All 3 patients had been exposed to vedolizumab: one had an underlying malignancy (colon adenocarcinoma), the 2 others also had been exposed to corticosteroids prior to colectomy. No VTE was seen in the patients who underwent colectomy while on tofacitinib. Conclusion The overall risk for UC patients to develop VTE after colectomy is low with adequate antithrombotic prophylactic therapy. In particular, we did not observe any VTE in our colectomy patients who were exposed to tofacitinib prior to surgery. The three patients who developed VTE despite LMWH had additional risk factors (concomitant steroid use, active cancer).

Prior Immunogenicity to Anti-TNF Biologics Is Not Associated with Increased Anti-drug Antibodies to Vedolizumab or Ustekinumab

Patients with inflammatory bowel disease (IBD) on biologic therapy may lose response to anti-tumor necrosis factor agents (anti-TNFs) due to the development of anti-drug antibodies (ADAs). A history of anti-TNF ADA increases the risk of developing ADA to subsequent anti-TNFs; however, it is not known whether ADA to anti-TNFs increases the risk of ADA development to vedolizumab (VDZ) or ustekinumab (UST). We aimed to investigate whether prior history of ADA to anti-TNF increases the risk of ADA to VDZ and UST. We conducted a retrospective cohort study of patients at a tertiary care IBD center over the course of four years who had previous anti-TNF drug and ADA level data during maintenance treatment and subsequent VDZ or UST drug and antibody levels, all collected as standard of care. The primary outcome was the rate of ADA development to VDZ and UST in patients with and without prior anti-TNF immunogenicity. Descriptive statistics summarized the data and univariate tested associations. Of the 152 IBD patients analyzed, 41 (27%) had a history of previous anti-TNF ADA with 22 (53.7%) having simultaneously undetectable anti-TNF drug levels. There was no significant difference in the rates of ustekinumab and vedolizumab ADA development between patients with prior ADA and patients without prior ADA (1/41 [2.7%] vs 1/111 [0.9%]; p = 0.54). There was also no difference in concomitant immunomodulator use with ustekinumab or vedolizumab initiation in patients with or without prior ADA (13/41 [31.7%] vs 31/111 [27.9%], p = 0.84). Neither patient who developed ADA to VDZ or UST was on concomitant immunomodulator at drug initiation, and both patients had detectable drug levels at the time of antibody detection. We observed that prior immunogenicity to anti-TNF agents does not confer an increased risk of immunogenicity to ustekinumab or vedolizumab. Our data support the use of vedolizumab or ustekinumab as monotherapy for the treatment of IBD.

Changes in disease behaviour and location and factor analysis in patients with Crohn's disease undergoing repeated-resections.

Crohn's disease affects the entire gastrointestinal tract and is accompanied by changes in disease location and behaviour. We aimed to analyse changes and the factors in patients with Crohn's disease undergoing intestinal repeated-resection. We included and retrospectively analyzed patients with Crohn's disease who received ≥2 bowel surgeries from a tertiary inflammatory bowel disease centre from January 2008 to December 2019. The Montreal classification was used to describe the disease site and behaviour. Factors were assessed by univariate and multivariate analysis. A total of 339 patients were included of whom 94 patients received ≥3 bowel resections. The median patient's age at the second and third surgery was 36.4 and 39.6, respectively. Repeated-resection most commonly occurred in the original surgical site. However, disease behaviour progressed with the number of surgical interventions and disease duration, especially for patients with B1 phenotype. Patients with L1 Crohn's disease at a primary resection that progressed to L2 Crohn's disease at a second surgical resection required a resection earlier than patients whose disease remained in L1 or progressed to L3 Crohn's disease. Multivariate analysis showed that history of appendectomy was a predictor of progression from L1 to L3 Crohn's disease at a second surgical resection, while treatment with azathioprine (AZA) may be a protective factor that abated the risk of progression from L1 to L3 Crohn's disease. The original resection site is the most common location for recurrence in patients with Crohn's disease, but disease behaviour progresses with the number of surgeries and disease duration. L1 Crohn's disease patients with a history of appendectomy have a higher risk to progress to L3 Crohn's disease at a second surgical resection, while the AZA may be a protective factor that reduces the risk of progression from L1 to L3.

Anti-tumor necrosis factor-induced lupus in patients with inflammatory bowel disease: a hospital-based cohort study from Korea.

Background:Anti-tumor necrosis factor (TNF) agents are increasingly used for rheumatic diseases and inflammatory bowel disease (IBD), but are associated with the development of anti-TNF-induced lupus (ATIL). Nonetheless, few ATIL studies on non-Caucasian IBD patients exist. Here, we investigated the incidence, clinical features, and risk factors of ATIL in Korea.Methods:We retrospectively reviewed the medical records of IBD patients undergoing anti-TNF therapy at our tertiary IBD center between 2008 and 2020. ATIL was diagnosed as a temporal association between symptoms and anti-TNF agents, and the presence of at least one serologic and non-serologic American College of Rheumatology criterion. The risk factors for ATIL occurrence were assessed using multivariate Cox regression analysis.Results:Of 1362 IBD patients treated with anti-TNF agents, 50 (3.7%) ATIL cases were suspected, of which 14 (1.0%) received a definitive diagnosis. Arthritis and mucocutaneous symptoms were observed in 13 and 4 patients, respectively. All ATIL cases were positive for anti-nuclear and anti-dsDNA antibodies. Four patients (30.8%) improved while continuing anti-TNF therapy. At the final follow up, the ATIL group (n = 14) had a lower IBD remission rate (30.8% versus 68.8%, p = 0.019) than the non-ATIL group (n = 36). Ulcerative colitis and longer disease duration were associated with ATIL occurrence, with hazard ratios of 7.017 (p = 0.005) and 1.118 (p = 0.002), respectively.Conclusion:Although rare, ATIL is associated with poor treatment response to IBD in Korean patients. ATIL should be considered if arthritis and mucocutaneous symptoms develop during anti-TNF therapy for IBD.

Real-World Effectiveness and Safety of Ustekinumab for Ulcerative Colitis From 2 Tertiary IBD Centers in the United States.

Ustekinumab has been recently approved for the treatment of moderately to severely active ulcerative colitis (UC). The registry trials for ustekinumab in UC demonstrated efficacy and safety, but data on real-world outcomes are limited. We describe the effectiveness and safety of ustekinumab in patients with UC from 2 US tertiary inflammatory bowel disease centers. Patients with moderately to severely active UC treated with ustekinumab at NYU Langone Health (New York, New York) and University of Chicago Medical Center (Chicago, Illinois) between January 2016 and March 2020 were retrospectively included. The primary outcome was clinical remission at 3 and 12 months, defined as a partial Mayo score of ≤2, with a combined rectal bleeding and stool frequency subscore of ≤1. Sixty-six UC patients were included. Ninety-two percent of patients had prior exposure to biologics or tofacitinib. Forty-three percent and 45% of patients achieved clinical remission by 3 and 12 months, respectively. Anti-TNF nonresponse and endoscopic Mayo score of 3 were negative predictors of clinical remission. Thirty-three percent of those followed for a year achieved concurrent endoscopic and histologic healing, which was significantly associated with lower partial Mayo score (P < 0.01) and lower stool frequency (P = 0.02). Serious adverse events occurred in 4 (6%) patients (3 UC exacerbations, 1 vasculitis). In this cohort of mostly biologic-refractory UC patients, treatment with ustekinumab achieved remission in nearly half of them at 12 months, and was associated with an overall favorable safety profile. These results are modestly better than the pivotal trials.

COVID-19 in IBD: The experience of a single tertiary IBD center

BackgroundItaly has been one of the most affected countries in the world by COVID-19. There has been increasing concern regarding the impact of COVID‐19 on patients with inflammatory bowel disease (IBD), particularly in patients treated with immunosuppressants or biologics. The aim of our study is to understand the incidence of COVID-19 in a large cohort of patients with IBD. Furthermore, we analyzed possible risk factors for infection and severity of COVID-19. MethodsThis was an observational study evaluating the impact of COVID-19 on IBD patients in a single tertiary center. A 23 multiple-choice-question anonymous survey was administered to 1200 patients with IBD between March 10th and June 10th 2020. Results1158 questionnaires were analyzed. The majority of patients had Crohn's disease (CD) (60%) and most of them were in clinical remission. Among the 26 patients (2.2%) who tested positive for COVID-19, only 5 (3CD) were on biological treatment and none required hospitalization. Two patients died and were on treatment with mesalazine only. Of the 1158 patients, 521 were on biological therapy, which was discontinued in 85 (16.3%) and delayed in 195 patients (37.4%). A worsening of IBD symptoms was observed in 200 patients on biological therapy (38.4%). Most of these patients, 189 (94.5%), had stopped or delayed biological treatment, while 11 (5.5%) had continued their therapy regularly (p<0.001). ConclusionsOur data are in line with the current literature and confirm a higher incidence compared to the general population. Biological therapy for IBD seems to not be a risk factor for infection and should not be discontinued in order to avoid IBD relapse.

The Burden of Anemia Remains Significant over Time in Patients with Inflammatory Bowel Diseases at a Tertiary Referral Center.

Anemia is a common complication of inflammatory bowel diseases (IBD), as well as a predictor of poor outcomes. The aim of this study was to determine the prevalence of anemia over time and the management of moderate to severe anemia at a tertiary referral IBD center. We retrospectively reviewed the occurrence of anemia at the time of referral or diagnosis and during follow-up at the McGill University Health Centre IBD center. Consecutive patients presenting with an outpatient visit between July and December 2016 and between December 2018 and March 2019 were included. Disease characteristics, biochemistry and medical management, including the need for intravenous iron therapy were recorded. 1,356 Crohn's disease (CD) and 1,293 ulcerative colitis (UC) patients [disease duration: 12 (IQR: 6-22) and 10 (IQR: 5-19) years respectively] were included. The prevalence of moderate to severe anemia at referral/diagnosis (15.4% and 8.5%) and during follow-up (11.1% and 8.1%) were higher in CD than in UC patients. In CD, previous resective surgery, perianal disease and elevated C-reactive protein (CRP) at assessment, while in UC steroid therapy, an elevated CRP and fecal calprotectin at assessment were associated with anemia in a multivariate analysis. Anemia improved by >2g/dL in 56.5% after 4-6 weeks (intravenous iron dose >1000 mg in 87% of patients). Anemia occurred frequently in this IBD cohort, at referral to the center and during follow-up, and contributes to the burden of IBD in referral populations. Most patients were assessed for anemia regularly and with accurate anemia workup; however, the targeted management of moderate to severe anemia was suboptimal.

S0873 Patient and Gastroenterologist Attitudes of Fecal Microbiota Transplantation as a Treatment for Inflammatory Bowel Disease

INTRODUCTION: Fecal microbiota transplantation (FMT) is an attractive therapeutic option for patients with inflammatory bowel disease (IBD). While recent studies have shown benefit of FMT in UC, there are no guidelines for the use of FMT in IBD and current regulations limit FMT to treat C difficile infections. Despite these constraints, patients have used FMT for IBD. Our aim is to assess interest and attitudes of patients as well as current clinical practices and attitudes of gastroenterologists as it relates to FMT as therapy for IBD. METHODS: We performed IRB-approved cross-sectional web-based surveys of both patients and providers at a tertiary IBD center from November 2019 to January 2020. All English-speaking patients ≥18 years old with a self-reported diagnosis of IBD were eligible. RESULTS: 100 patients completed the study, 55% female, 56% with Crohn’s, 39% with UC and 5% with IBD-U (Table 1). 40% of patients had heard about FMT as treatment for IBD, though only 12% had discussed it with their GI. No patients had used FMT, but 17% had considered it for their IBD. Most patients (68%) felt more comfortable discussing FMT with their GI after this survey. Patients’ biggest concern of FMT was risk of infection. When told that the FDA recently reported a death related to drug resistant bacteria from FMT, most (53.3%) patients said this changed the way they felt about FMT. 56 providers (GIs) completed the study, 159 were approached: including 19 GI fellows, 22 General GI and 15 IBD specialists with a median of 14 years (range 0-56) in practice. Only 23% of GIs typically ask patients about FMT to treat IBD, though a majority (75%) report that a patient has previously asked them about FMT. A quarter of providers report that their patients have used FMT to treat IBD. Most GIs (84%) have referred a patient for FMT, most commonly for C difficile. The majority of GIs (86%) would consider entering IBD patients into FMT clinical trials. GIs’ biggest concern of FMT was lack of evidence (Figure 2). CONCLUSION: There was a significant minority (17%) of patients that have considered using FMT as a treatment for IBD, but only 23% of providers are asking their patients about FMT. Patients and providers had very different concerns about FMT, with patients concerned about risk of infection and GIs concerned about lack of evidence and efficacy. There is an opportunity to provide resources to providers to help initiate these conversations, and to educate patients on the risks and benefits of FMT for IBD.Table 1.: Characteristics of the Patient Population. Demographics of a patient population for a survey evaluating the patient perceptions and opinions of patients towards fecal microbiota transplantation (FMT) as a treatment for inflammatory bowel disease (IBD) performed at a single tertiary care centerFigure 1.: Patients' Concerns. Graph of patients concerns' about FMT as a treatment for IBD. For those patients with concerns about FMT we asked them to rank their concerns from biggest concern to least concern.Figure 2.: Gastroenterologists' Concerns. Graph of gastroenterologists' concerns regarding FMT as a potential treatment for IBD. We asked them to rank their concerns from most concerning to least concerning.

S0777 Time Trend Analysis of Pre-Operative Characteristics and Post-Operative Pouch Outcomes in UC Patients Undergoing Ileal Pouch Anal-Anastomosis

INTRODUCTION: Proctocolectomy and ileal pouch anal anastomosis (IPAA) is the treatment of choice for patients with medically resistant ulcerative colitis. In this retrospective cohort study, we aimed to observe trends in pre-operative characteristics and post-operative pouch outcomes experienced by patients undergoing IPAA based on the decade of the surgery. METHODS: We obtained electronic medical record data from patients at our tertiary Inflammatory Bowel Disease Center. Patients with a pre-operative diagnosis of UC who underwent an IPAA procedure between January 1990 and May 2017 were included in this study and were followed until December 31, 2019. We stratified the data according to the decade of surgery and assessed differences between groups using t-tests for continuous data and Chi-square tests for categorical variables. We used Kaplan Meier curves to visualize the probability of pouch survival based on the decade of surgery. We also created a Cox proportional hazards model and adjusted for covariates to determine factors associated with pouch failure (defined as pouch excision). RESULTS: A total of 322 patients were included in the study and the median length of follow-up was 8.9 years. 10% of patients experienced pouch failure. Over time, there was a significant increase in the percentage of patients treated with anti-TNF therapies before surgery, the number of IPAAs conducted with stapled anastomoses, and the number of three-stage surgical procedures (Table 1). Pouch survival analysis stratified by decade of surgery demonstrated a significant decrease in the probability of pouch survival in more recent years (Figure 1). A Cox proportional hazard model adjusted for covariates showed that patients having an IPAA in the 2000s or 2010s had 5-times (AHR: 4.68; 95% CI: (1.43–15.34), P < 0.05) and 17-times (AHR: 17.23 95% CI: (3.51–84.57), P < 0.001) greater likelihoods of pouch failure, respectively, than patients who had their surgeries in the 1990s (Table 2). CONCLUSION: This study demonstrates that the likelihood of pouch failure in patients who underwent surgery in the most recent decade is greater than those who underwent surgeries in prior decades. Increased exposure to anti-TNF therapies in this population suggests that these patients may have more refractory disease. Additional studies should be conducted in order to further elucidate the underlying drivers of this association.Table 1.: Study PopulationTable 2.: Adjusted Cox Proportional Hazard Model For Pouch Failure. A Cox proportional hazards model was used to determine factors associated with pouch failure (defined as pouch excision). The multivariable model included all variables found to be statistically significant in univariable analyses along with covariates thought to be associated with pouch failure. A P-value less than 0.05 was considered to be statistically significantFigure 1.: Pouch Survival Probability For UC Patients Based on Decade of IPAA. Data were stratified according to the decade that surgery was performed. For patients who underwent multi-stage procedures, this was defined as the decade that the first stage was performed. Statistical differences between groups were determined using a log-rank test and a P-value less than 0.05 was considered statistically significant.

The Effect of Adiposity on Anti-Tumor Necrosis Factor-Alpha Levels and Loss of Response in Crohn's Disease Patients.

INTRODUCTION:A high body mass index is known to adversely affect antitumor necrosis factor-alpha trough levels and secondary loss of response (SLOR) in patients with Crohn's disease. We hypothesize that high levels of adiposity negatively affect these outcomes and aimed to determine if this relationship exists.METHODS:We performed a retrospective cross-sectional study of 69 patients with Crohn's disease from two tertiary inflammatory bowel disease centers between February 1, 2015, and June 30, 2018. Primary responders to infliximab (IFX) or adalimumab (ADA) who had a trough level performed within 6 months of CT or MRI scan and at least 12 months of clinical follow-up were eligible for inclusion. Body composition as measured on CT/MRI scans were correlated with trough concentration and time SLOR. Multivariate adjustments were made for established risk factors known to affect trough levels and SLOR.RESULTS:Of 69 included patients, 44 (63.8%) and 25 (36.2%) patients received IFX and ADA, respectively. Multivariate analysis revealed that IFX trough concentrations were inversely correlated with visceral fat area (−0.02 [−0.04, −0.003], P = 0.03), visceral fat index (−0.07 [−0.12, −0.01], P = 0.02) and visceral fat: skeletal muscle area ratio (−3.81 [−7.13, −0.50], P = 0.03), but not body mass index (−0.23 [−0.52, 0.06], P = 0.11). No predictive factors were found for ADA. Increased total adipose area was associated with an increased risk of SLOR in ADA-treated patients, but not IFX-treated patients (hazard ratio = 1.01 [1.002, 1.016], P = 0.011).DISCUSSION:Visceral adiposity is an important predictor of IFX trough levels, and high total adiposity predicts for SLOR to ADA.

Impact of COVID-19 on diagnosis and management of paediatric inflammatory bowel disease during lockdown: a UK nationwide study.

COVID-19 has impacted on healthcare provision. Anecdotally, investigations for children with inflammatory bowel disease (IBD) have been restricted, resulting in diagnosis with no histological confirmation and potential secondary morbidity. In this study, we detail practice across the UK to assess impact on services and document the impact of the pandemic. For the month of April 2020, 20 tertiary paediatric IBD centres were invited to contribute data detailing: (1) diagnosis/management of suspected new patients with IBD; (2) facilities available; (3) ongoing management of IBD; and (4) direct impact of COVID-19 on patients with IBD. All centres contributed. Two centres retained routine endoscopy, with three unable to perform even urgent IBD endoscopy. 122 patients were diagnosed with IBD, and 53.3% (n=65) were presumed diagnoses and had not undergone endoscopy with histological confirmation. The most common induction was exclusive enteral nutrition (44.6%). No patients with a presumed rather than confirmed diagnosis were started on anti-tumour necrosis factor (TNF) therapy.Most IBD follow-up appointments were able to occur using phone/webcam or face to face. No biologics/immunomodulators were stopped. All centres were able to continue IBD surgery if required, with 14 procedures occurring across seven centres. Diagnostic IBD practice has been hugely impacted by COVID-19, with >50% of new diagnoses not having endoscopy. To date, therapy and review of known paediatric patients with IBD has continued. Planning and resourcing for recovery is crucial to minimise continued secondary morbidity.

Effect of Vedolizumab on Anemia of Chronic Disease in Patients with Inflammatory Bowel Diseases.

Background: Anemia of Chronic Disease (ACD) can negatively influence the clinical course of Inflammatory Bowel Disease (IBD) patients. The aim of this study was to evaluate the effect of Vedolizumab on ACD in IBD. Methods: Clinical data of 75 IBD patients (25 Crohn’s disease (CD) and 50 Ulcerative Colitis (UC)) receiving Vedolizumab in a tertiary referral IBD center were retrospectively evaluated and the effect of the drug on ACD was ascertained at weeks 14 and 24. Results: ACD was diagnosed in 35 (11 CD and 24 UC) out of 75 (47%) IBD patients. At both week 14 and week 24, improvements and resolutions of ACD were achieved by 13/35 (37%) and 11/35 (31%) patients, respectively. Baseline demographic/clinical characteristics did not differ between patients with ACD improvements/resolutions and those with persistent ACD. Clinical response occurred more frequently in patients who achieved ACD resolution (10/11, 91%) than in those without ACD improvement (5/11, 45%, p = 0.022). When analysis was restricted to anemic patients, ACD resolution was documented in 10/22 patients (45%) achieving clinical response and 1/13 of non-responders (8%; p = 0.02). Conclusions: ACD occurs in half of the IBD patients and, in nearly two thirds of them, Vedolizumab treatment associates with ACD resolution/improvement.

Gastroenterologist-Lead Management of Iron Deficiency Anemia in Inflammatory Bowel Disease Is Effective, Safe, and May Increase Quality of Life.

BackgroundThe effectiveness and safety of gastroenterologist (GI)-lead treatment of iron deficiency anemia (IDA) in inflammatory bowel disease (IBD) have not been well-studied.MethodsA retrospective chart review of patients with IBD, IDA, and evidence of treatment with iron at a tertiary IBD center was conducted.ResultsIn 351 patients, hemoglobin and quality of life scores increased significantly after treatment with iron. Twelve of 341 patients treated with intravenous iron had an adverse effect. Twenty-seven patients required a hematology referral.ConclusionGIs should consider treating patients with IBD and IDA with intravenous iron as it is safe and effective.

Providing Hospitalized Ulcerative Colitis Patients With Practice Guidelines Improves Patient-Reported Outcomes.

Background and aimsVariation in care has been demonstrated among hospitalized patients with ulcerative colitis. Guidelines aim to reduce variation; however, it is known that the uptake of guidelines by physicians is variable. Providing patients with guidelines is a strategy that has not been extensively studied in inflammatory bowel disease (IBD). Our aim was to evaluate the impact of a patient-directed educational intervention that included treatment guidelines among hospitalized ulcerative colitis patients.MethodsWe performed a quality improvement, cluster-randomized trial at seven tertiary IBD centres. Sites were randomized to implement an educational intervention or standard care for a 6-month period between January 2017 and January 2018. The educational intervention consisted of a patient-directed video that provided a summary of inpatient management guidelines for ulcerative colitis. Primary outcome measures included the length of stay and colectomy at discharge and 6 months. Patient-reported outcomes included trust in physician and patient satisfaction at discharge and at 6 months.ResultsNinety-one patients were enrolled. No statistically significant differences in length of stay or colectomy were noted. Patients who received the intervention had higher trust in physician as measured by Trust in Physician Score at discharge (69.5 vs. 62.6, P = 0.028) and at 6 months (77.7 vs. 68, P = 0.008). Patient satisfaction as measured by the CACHE questionnaire in the intervention group was higher at discharge (72.8 vs. 67.1, P = 0.04); however, this difference was not sustained.ConclusionEmpowering patients with guidelines through an educational intervention resulted in differences in trust in physician and patient satisfaction. Further studies are needed for evaluating a strategy of engaging IBD patients to take a more active role in their care. (clinicaltrials.gov, NCT02569333).

Predictors of High Health Care Utilization in Patients With Inflammatory Bowel Disease Within 1 Year of Establishing Specialist Care.

A small proportion of patients with inflammatory bowel disease (IBD) consume a disproportionate amount of health care resources, with most of these spent on unplanned care in emergency room (ER) and hospital visits. Interventions in those at high risk in the outpatient setting could reduce the need for future inpatient care. We sought to describe the characteristics predictive of high health care utilization within 1 year after an initial IBD clinic encounter. This was a retrospective study of new IBD patients seen at the outpatient clinics of 2 tertiary IBD centers in the United States. Baseline sociodemographic and clinical characteristics were collected, and the number of IBD-related ER and hospital visits were recorded over the 1-year period after the initial clinic encounter. Patients with ≥2 visits (high utilizers) were compared with those with no visits. Of the 735 patients included in the final analysis, 106 (14.4%) were high utilizers, and they had a mean of 2.9 visits (maximum = 10) in the 1 year after their initial encounter. In multivariate analysis, insurance coverage through medical assistance (odds ratio [OR] 3.57; 95% confidence interval [CI], 1.38-9.20), steroid use (OR 1.83; 95% CI, 1.11-3.04), short inflammatory bowel disease questionnaire score <50 (OR 2.29; 95% CI, 1.23-4.27), and current ostomy (OR 4.82; 95% CI, 1.51-15.37) were independently associated with high utilization. Multidisciplinary care and resources should be preferentially channeled towards new clinic patients with severe disease and on medical assistance, as this could reduce future inpatient visits and result in cost savings.

Su1030 ENDOSCOPIC STRICTUROTOMY – A NOVEL THERAPEUTIC MODALITY FOR IBD-RELATED STRICTURES: FIRST EUROPEAN EXPERIENCE

Strictures, both primary and secondary anastomotic strictures, are common complications in patients with inflammatory bowel diseases (IBD) especially Crohn's disease (CD). Balloon dilation has been the gold standard in the endoscopic treatment of these strictures. Endoscopic stricturotomy (ESt) represent a promising novel approach, however, the data published on this method so far is limited to a single US center. All ESts performed in IBD patients between September 2018 and November 2019 in our tertiary IBD center were included. Data on demographics, disease characteristics, procedure details and outcomes were analyzed. Technical success was defined as an ability to pass the scope through the stricture following the procedure. In total, 46 procedures were performed in 39 patients (34 with Crohn's disease, CD, and 5 with ulcerative colitis, UC) Among these 38.5% were males. Mean age was 43.5±10.9 years and mean disease duration was 17.4±9.9 years. Single ESt was done in 82.1% of patients, while 17.9% required multiple procedures. Most common location of stricture was surgical anastomosis site (43, 93.5%), while remaining 3 were located at anal canal. Anastomotic strictures included ileo-colonic (71.7%), ileo-rectal (4.3%), and ileal pouch-anal (17.4%) anastomoses. Previous endoscopic balloon dilation (EBD) was attempted in 78.3% cases. Technical success was achieved in 42 ESts (91.3%), complications occurred in two cases (both delayed bleeding, managed conservatively). After the mean follow-up time of 8.2±4.3 months, cumulative probability of reintervention (ESt, EBD or surgery) at 6 months was 16.1% (95% CI 1.7-44.2%). ESt is a novel endoscopic technique, which is both highly efficacious and safe to be performed in patients with IBD-related strictures.