Safety of Immunosuppression in a Prospective Cohort of Inflammatory Bowel Disease Patients With a HIstoRy of CancEr: SAPPHIRE Registry.

BACKGROUND & AIMS: In patients with inflammatory bowel disease (IBD) and a history of cancer, retrospective studies have suggested that exposure to immunosuppressive agents does not increase the risk of incident (recurrent or new) cancer compared with unexposed patients. SAPPHIRE is a prospective registry aimed at addressing this issue. METHODS: Since 2016, patients with IBD and confirmed index cancer before enrollment were followed up annually. Patients receiving chemotherapy or radiation at enrollment, or recurrent cancer within 5 years, were excluded. The primary outcome was development of incident cancer related to exposure to immunosuppressive medications. RESULTS: Among 305 patients (47% male, 88% white), the median age at IBD diagnosis and cancer were 32 and 52 years, respectively. Index cancers were solid organ (46%), dermatologic (32%), gastrointestinal (13%), and hematologic (9%). During a median follow-up period of 4.8 years, 210 patients (69%) were exposed to immunosuppressive therapy and 46 patients (15%) developed incident cancers (25 new, 21 recurrent). In unadjusted analysis, the crude rate of incident cancer in unexposed patients was 2.58 per 100 person-years vs 4.78 per 100 person-years (relative risk, 1.85; 95% CI, 0.92-3.73) for immunosuppression-exposed patients. In a proportional hazards model adjusting for sex, smoking history, age and stage at index malignancy, and nonmelanoma skin cancer, no significant association was found between receipt of immunosuppression and incident cancer (adjusted hazard ratio, 1.41; 95% CI, 0.69-2.90), or with any major drug class. CONCLUSIONS: In this interim analysis of patients with IBD and a history of cancer, despite numerically increased adjusted hazard ratios, we did not find a statistically significant association between subsequent exposure to immunosuppressive therapies and development of incident cancers.

A Review of Available Medical Therapies to Treat Moderate-to-Severe Inflammatory Bowel Disease.

The treatment armamentarium for inflammatory bowel disease has expanded rapidly in the past several years with new biologic and small molecule-agents approved for moderate-to-severe ulcerative colitis and Crohn's disease. This has made treatment selection more challenging with limited but evolving guidance as to where to position each medication. In this review, we discuss the efficacy data for each agent approved in the United States by reviewing their phase 3 trial data and other comparative effectiveness studies. In addition, safety considerations and use in special populations are summarized with proposed algorithms for positioning therapies. The aim is to provide a synopsis of high-impact data and aid in outpatient treatment decision-making for patients with inflammatory bowel disease.

Changes in Therapy Are Not Associated With Increased Remission in Patients With Crohn's Disease of the Pouch.

INTRODUCTION: There is a paucity of data on the real-world effectiveness of therapies in patients with Crohn's disease of the pouch. METHODS: This was a prospective multicenter study evaluating the primary outcome of remission at 12 months of therapy for Crohn's disease of the pouch. RESULTS: One hundred thirty-four patients were enrolled. Among the 77 patients with symptoms at baseline, 35 (46.7%) achieved remission at 12 months. Of them, 12 (34.3%) changed therapy. There was no significant association between therapy patterns and remission status. DISCUSSION: Approximately 50% with symptoms at enrollment achieved clinical remission at 12 months, most of whom did so without a change in therapy.

The Real-World Effectiveness and Safety of Ustekinumab in the Treatment of Crohn's Disease: Results From the SUCCESS Consortium.

INTRODUCTION: We evaluated the real-world effectiveness and safety of ustekinumab (UST) in patients with Crohn's disease (CD). METHODS: This study used a retrospective, multicenter, multinational consortium of UST-treated CD patients. Data included patient demographics, disease phenotype, disease activity, treatment history, and concomitant medications. Cumulative rates of clinical, steroid-free, endoscopic, and radiographic remissions were assessed using time-to-event analysis, and clinical predictors were assessed by using multivariate Cox proportional hazard analyses. Serious infections and adverse events were defined as those requiring hospitalization or treatment discontinuation. RESULTS: A total of 1,113 patients (51.8% female, 90% prior antitumor necrosis factor exposure) were included, with a median follow-up of 386 days. Cumulative rates of clinical, steroid-free, endoscopic, and radiographic remissions at 12 months were 40%, 32%, 39%, and 30%, respectively. Biologic-naive patients achieved significantly higher rates of clinical and endoscopic remissions at 63% and 55%, respectively. On multivariable analyses, prior antitumor necrosis factor (hazard ratio, 0.72; 95% confidence interval, 0.49-0.99) and vedolizumab exposure (hazard ratio, 0.65; 95% confidence interval, 0.48-0.88) were independently associated with lower likelihoods of achieving endoscopic remission. In patients who experienced loss of remission, 77 of 102 (75%) underwent dose optimization, and 44 of 77 (57%) achieved clinical response. An additional 152 of 681 patients (22.3%) were dose-optimized because of primary nonresponse incomplete response to UST, of whom 40.1% (61 of 152) responded. Serious infections occurred in 3.4% of patients while other noninfectious adverse events (lymphoma [n = 1], arthralgia [n = 6], rash [n = 6], headache [n = 3], hepatitis [n = 3], hair loss [n = 3], neuropathy [n = 1], and vasculitis [n = 1]) occurred in 2.4% of patients. DISCUSSION: UST represents a safe and effective treatment option for CD, with 40% of patients from a highly refractory cohort achieving clinical remission by 12 months. The greatest treatment effect of UST was seen in biologic-naive patients, and dose escalation may recapture clinical response.

Single-Cell Transcriptional Survey of Ileal-Anal Pouch Immune Cells From Ulcerative Colitis Patients.

BACKGROUND & AIMS: Restorative proctocolectomy with ileal pouch-anal anastomosis is a surgical procedure in patients with ulcerative colitis refractory to medical therapies. Pouchitis, the most common complication, is inflammation of the pouch of unknown etiology. To define how the intestinal immune system is distinctly organized during pouchitis, we analyzed tissues from patients with and without pouchitis and from patients with ulcerative colitis using single-cell RNA sequencing (scRNA-seq). METHODS: We examined pouch lamina propria CD45+ hematopoietic cells from intestinal tissues of ulcerative colitis patients with (n = 15) and without an ileal pouch-anal anastomosis (n = 11). Further in silico meta-analysis was performed to generate transcriptional interaction networks and identify biomarkers for patients with inflamed pouches. RESULTS: In addition to tissue-specific signatures, we identified a population of IL1B/LYZ+ myeloid cells and FOXP3/BATF+ T cells that distinguish inflamed tissues, which we further validated in other scRNA-seq datasets from patients with inflammatory bowel disease (IBD). Cell-type-specific transcriptional markers obtained from scRNA-seq was used to infer representation from bulk RNA sequencing datasets, which further implicated myeloid cells expressing IL1B and S100A8/A9 calprotectin as interacting with stromal cells, and Bacteroidales and Clostridiales bacterial taxa. We found that nonresponsiveness to anti-integrin biologic therapies in patients with ulcerative colitis was associated with the signature of IL1B+/LYZ+ myeloid cells in a subset of patients. CONCLUSIONS: Features of intestinal inflammation during pouchitis and ulcerative colitis are similar, which may have clinical implications for the management of pouchitis. scRNA-seq enables meta-analysis of multiple studies, which may facilitate the identification of biomarkers to personalize therapy for patients with IBD. The processed single cell count tables are provided in Gene Expression Omnibus; GSE162335. Raw sequence data are not public and are protected by controlled-access for patient privacy.

Comparative Safety and Effectiveness of Vedolizumab to Tumor Necrosis Factor Antagonist Therapy for Ulcerative Colitis.

BACKGROUND & AIMS: We aimed to compare safety and effectiveness of vedolizumab to tumor necrosis factor (TNF)-antagonist therapy in ulcerative colitis in routine practice. METHODS: A multicenter, retrospective, observational cohort study (May 2014 to December 2017) of ulcerative colitis patients treated with vedolizumab or TNF-antagonist therapy. Propensity score weighted comparisons for development of serious adverse events and achievement of clinical remission, steroid-free clinical remission, and steroid-free deep remission. A priori determined subgroup comparisons in TNF-antagonist-naïve and -exposed patients, and for vedolizumab against infliximab and subcutaneous TNF-antagonists separately. RESULTS: A total of 722 (454 vedolizumab, 268 TNF antagonist) patients were included. Vedolizumab-treated patients were more likely to achieve clinical remission (hazard ratio [HR], 1.651; 95% confidence interval [CI], 1.229-2.217), steroid-free clinical remission (HR, 1.828; 95% CI, 1.135-2.944), and steroid-free deep remission (HR, 2.819; 95% CI, 1.496-5.310) than those treated with TNF antagonists. Results were consistent across subgroup analyses in TNF-antagonist-naïve and -exposed patients, and for vedolizumab vs infliximab and vs subcutaneous TNF-antagonist agents separately. Overall, there were no statistically significant differences in the risk of serious adverse events (HR, 0.899; 95% CI, 0.502-1.612) or serious infections (HR, 1.235; 95% CI, 0.608-2.511) between vedolizumab-treated and TNF-antagonist-treated patients. However, in TNF-antagonist-naïve patients, vedolizumab was less likely to be associated with serious adverse events than TNF antagonists (HR, 0.192; 95% CI, 0.049-0.754). CONCLUSIONS: Treatment of ulcerative colitis with vedolizumab is associated with higher rates of remission than treatment with TNF-antagonist therapy in routine practice, and lower rates of serious adverse events in TNF-antagonist-naïve patients.

P024 Anorectal Manometry in Patients with Fecal Incontinence After Ileal Pouch-Anal Anastomosis for Inflammatory Bowel Disease: A Cohort Study.

BACKGROUND: Fecal incontinence (FI) affects up to 1 in 4 patients with inflammatory bowel disease (IBD) and is associated with inflammation, surgeries, and altered rectal sensitivity. Ileal pouch-anal anastomosis (IPAA) is a surgical intervention for select IBD patients to avoid a permanent stoma. High-resolution anorectal manometry (HRAM) studies in IBD patients with FI demonstrate lower resting pressures and rectal sensory dysfunction. However, HRAM data in IBD patients with FI post-IPAA remains limited. We hypothesized patients with FI would have lower resting and squeeze pressures and rectal hypersensitivity compared to healthy controls and that these changes would be similar after IPAA. METHODS: Retrospective review of prospectively collected data was conducted on patients undergoing HRAM from 2017-2021 at a single urban academic medical center. Patient characteristics (age, gender, BMI, stool frequency, diabetes, pregnancy history) and surgical history (prior perianal surgery, index vs. re-do IPAA) were obtained. HRAM variables included rectoanal inhibitory reflex (RAIR), sphincter length, resting, squeeze, cough, and push pressures, sensation thresholds (first sensation, constant sensation, desire to defecate, urgency to defecate, max tolerable volume), and balloon expulsion test (BET). HRAM outcomes in IPAA patients with FI (IPAA-FI) were compared to non-IBD patients with FI (non-IBD-FI). HRAM data for both patient cohorts were also compared to existing normative data of healthy controls. Non-IBD patients with constipation and FI were excluded from analysis. An independent samples t-test was performed (p < 0.05) for continuous variables, and chi-square test was used for categorical variables. RESULTS: Fifty-six patients (66% female) were in the non-IBD-FI group. Eighteen patients (67% female) were in the IPAA-FI group. Average age in the IPAA-FI cohort was 44.8 ± 13.6 vs. 66.3 ± 14.4 in the non-IBD-FI group (p< 0.01). Sphincter length in the IPAA-FI group was 2.7 ± 1.1cm vs. 3.2 ± 0.6cm in the non-IBD-FI group (p=0.03). There was no significant difference in sensation thresholds or resting, squeeze, cough, and push pressures between the two groups. Urinary incontinence was observed in 5.6% of IPAA-FI patients vs. 44.6% of non-IBD-FI patients (p < 0.01). RAIR was present in 38.5% of IPAA-FI patients vs. 100% of non-IBD-FI patients (p < 0.01). Both patient cohorts had significantly shorter sphincter length, lower squeeze and push pressures, and lower sensation thresholds compared to normative data. Resting pressures for the IPAA-FI group was not significantly different compared to healthy controls. CONCLUSION: Overall, anorectal pressures and sensation are similar between IPAA-FI and non-IBD-FI patients. However, the underlying FI mechanism seems to differ. Higher rates of urinary incontinence in the non-IBD-FI cohort suggests global pelvic floor dysfunction compared to IPAA-FI patients who are younger and have post-operative neuromuscular dysfunction, as evidenced by shorter sphincter length and absent RAIR. Though rectal hypersensitivity and lower squeeze/push pressures are observed in both patient groups compared to healthy controls, normal resting pressure in IPAA-FI suggests that potentially different normative ranges are needed for this cohort to accurately assess post-surgical changes and guide pre-operative counseling.

Crohn Disease Active Inflammation Assessment with Iodine Density from Dual-Energy CT Enterography: Comparison with Histopathologic Analysis.

Background Dual-energy CT enterography (DECTE) has been shown to be useful in characterizing Crohn disease activity compared with clinical markers of inflammation but, to the knowledge of the authors, comparison has not been made with histopathologic specimens. Purpose To compare mucosal iodine density obtained at DECTE from Crohn disease-affected bowel with histopathologic specimens from surgically resected ileocolectomy bowel segments or terminal ileum colonoscopic biopsies in the same patients. Materials and Methods This was a retrospective study. Bowel segments in adults with Crohn disease who underwent DECTE from January 2017 to April 2019 within 90 days of ileocolectomy or colonoscopy were retrospectively evaluated with prototype software allowing the semiautomatic determination of inner hyperdense bowel wall (mucosal) mean iodine density, normalized to the aorta. Mean normalized iodine density and clinical activity indexes (Crohn Disease Activity Index [CDAI] and Harvey-Bradshaw Index [HBI]) were compared with histologic active inflammation grades by using two-tailed t tests. Receiver operating characteristic curves were generated for mean normalized iodine density, CDAI, and HBI to determine sensitivity, specificity, and accuracy. A P value less than .05 was considered to indicate statistical significance. Results The following 16 patients were evaluated (mean age, 41 years ± 14 [standard deviation]): 10 patients (five men, five women; mean age, 41 years ± 15) with 19 surgical resection specimens and six patients with terminal ileum colonoscopic mucosal biopsies (four men, two women; mean age, 43 years ± 14). Mean normalized iodine density was 16.5% ± 5.7 for bowel segments with no active inflammation (n = 8) and 34.7% ± 9.7 for segments with any active inflammation (n = 17; P < .001). A 20% mean normalized iodine density threshold had sensitivity, specificity, and accuracy of 17 of 17 (100%; 95% CI: 80.5, 100), six of eight (75%; 95% CI: 35, 97), and 23 of 25 (92%; 95% CI: 74, 99), respectively, for active inflammation. Clinical indexes were similar for patients with and without active inflammation at histopathologic analysis (CDAI score, 261 vs 251, respectively [P = .77]; HBI score, 7.8 vs 6.4, respectively [P = .36]). Conclusion Iodine density from dual-energy CT enterography may be used as a radiologic marker of Crohn disease activity as correlated with histopathologic analysis. © RSNA, 2021 See also the editorial by Ohliger in this issue.

Implementation of an Inpatient IBD Service Is Associated with Improvement in Quality of Care and Long-Term Outcomes.

BACKGROUND: There is wide variation in the quality of care of hospitalized patients with inflammatory bowel disease (IBD). Prior studies have demonstrated that a specialized inpatient IBD service improves short-term outcomes. In this study, we assessed the impact of a dedicated IBD service on the quality of care and long-term outcomes. METHODS: This retrospective cohort study included adult patients admitted for a complication of IBD between March 2017 and February 2019 to a tertiary referral center. In March 2018, a dedicated inpatient IBD service co-managed by IBD gastroenterologists and colorectal surgeons was implemented. Quality of care outcomes included C. difficile stool testing, confirmed VTE prophylaxis administration and opiate avoidance. Long-term outcomes were clinical remission, IBD-related surgery, ED visits, and hospital readmissions at 90 days and 12 months. RESULTS: In total, 143 patients were included; 66 pre- and 77 post-implementation of the IBD service. Fifty-two percent had ulcerative colitis and 48% had Crohn's disease. After implementation, there was improvement in C.difficile testing (90% vs. 76%, P = 0.04), early VTE prophylaxis (92% vs. 77%, P = 0.01) and decreases in narcotic use (14% vs. 30%, P = 0.02), IBD-related ED visits at 90 days (7% vs 18%, P = 0.03) and 12 months (16% vs 30%, P = 0.04), and IBD readmissions at 90 days (16% vs. 30%, P = 0.04). There were no differences in rates of clinical remission or surgery. CONCLUSIONS: The creation of a dedicated inpatient IBD service improved quality of IBD care and reduced post-discharge ED visits and readmissions and broader implementation of this strategy may help optimize care of hospitalized IBD patients.

Ustekinumab Does Not Increase Risk of Adverse Events: A Meta-Analysis of Randomized Controlled Trials.

GOALS AND BACKGROUND: Ustekinumab (UST) is a monoclonal antibody inhibitor of IL-12/IL-23 approved for the treatment of Crohn's disease (CD) and ulcerative colitis (UC). We conducted a meta-analysis to compare rates of adverse events (AEs) in randomized controlled trials (RCTs) of UST for all indications. STUDY: A systematic search was performed of MEDLINE, Embase, and PubMed databases through November 2019. Study inclusion included RCTs comparing UST to placebo or other biologics in patients aged 18 years or older with a diagnosis of an autoimmune condition. RESULTS: Thirty RCTs with 16,068 patients were included in our analysis. Nine thousand six hundred and twenty-six subjects were included in the UST vs placebo analysis. There was no significant difference in serious or mild/moderate AEs between UST and placebo with an OR of 0.83 (95% CI 0.66, 1.05) and 1.08 (95% CI 0.99, 1.18), respectively, over a median follow-up time of 16 weeks. In a sub-analysis of CD and UC trials, no difference in serious or mild/moderate AEs in UST versus placebo was seen. CONCLUSIONS: UST was not associated with an increase in short-term risk of AEs.

Fecal Microbiota Transplantation (FMT) with Colonoscopy Is Superior to Enema and Nasogastric Tube While Comparable to Capsule for the Treatment of Recurrent Clostridioides difficile Infection: A Systematic Review and Meta-Analysis.

BACKGROUND: Several routes of fecal microbiota transplantation (FMT) administration are available for treating recurrent Clostridioides difficile infections (CDI), the most recent of which are capsules. AIM: To assess the efficacy of colonoscopy, capsule, enema, and nasogastric tube (NGT) FMT for the treatment of recurrent CDI. METHODS: We reported clinical outcomes of colonoscopy, capsule, enema, and NGT FMT for the treatment of recurrent CDI according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. During January 2000 to January 2018, three databases were searched: PubMed, EMBASE, and CINAHL. Primary outcome was overall cure rate which was assessed using a random effects model; secondary outcomes included adverse effects as well as subgroup analyses comparing donor relationship, sample preparation, and study design. RESULTS: Twenty-six studies (1309 patients) were included in the study. FMT was administered using colonoscopy in 16 studies (483 patients), NGT in five studies (149 patients), enema in four studies (360 patients), and capsules in four studies (301 patients). The random effects of pooled FMT cure rates were colonoscopy 94.8% (CI 92.4-96.8%; I2 15.6%), capsule 92.1% (CI 88.6-95.0%; I2 7.1%), enema 87.2% (CI 83.4-90.5%; I2 0%), and NGT/NDT 78.1% (CI 71.6-84.1%; I2 0%). On subgroup analysis of colonoscopy FMT, sample preparation methods had comparable cure rates: fresh 94.9% compared to 94.5%. Similarly, cure rates were unaffected by donor relationship: mixed 94.5% compared to unrelated donor 95.7%. CONCLUSION: CDI cure rates with FMT performed with colonoscopy are superior to enema and NGT FMT, while those with FMT with colonoscopy and capsule are comparable.

Crohn Disease Prognostication With Semiautomatic Dual-Energy Computed Tomography Enterography-Derived Iodine Density.

OBJECTIVE: The objective of this study was to determine if dual-energy computed tomography enterography (DECTE)-obtained iodine density can predict medical management change or surgery in Crohn disease patients. METHODS: The most active-appearing bowel segment on DECTE in 21 Crohn disease patients was retrospectively interrogated with prototype software determining the percentage of bowel wall (I) in specified ranges. Patients were categorized into 3 groups after DECTE: (1) no management change, (2) outpatient medication change, and (3) inpatient admission or surgery. Crohn's disease activity index was calculated. Group 3's percentage iodine density of >3 mg/mL and Crohn's disease activity index were compared with group 1/2. Crohn's disease activity index and percentage iodine density of >2 mg/mL were compared for groups 2/3 versus group 1 patients. RESULTS: There were 5 group 1, 6 group 2, and 10 group 3 patients. Group 3 patients had higher frequency of iodine density >3 mg/mL (27%) compared with groups 1/2 patients (12.6%) (P < 0.05). Crohn's disease activity index was similar (P = 0.98). Groups 2/3 patients had 60.5% iodine density of >2 mg/mL, whereas group 1 patients had 31.7% iodine density of >2 mg/mL (P < 0.05). Crohn's disease activity index was similar (P = 0.12). CONCLUSIONS: Iodine density from DECTE may predict medical or surgical Crohn disease management.

Hormone Therapy for Cancer Is a Risk Factor for Relapse of Inflammatory Bowel Diseases.

BACKGROUND & AIMS: Exposure to hormone contraception has been associated with an increased risk of relapse of inflammatory bowel diseases (IBDs). Little is known about the effects of cancer therapies, specifically hormone therapies, on the course of IBD. METHODS: We conducted a retrospective cohort study, collecting data from 5 medical centers, on patients with IBD who received a subsequent diagnosis of breast or prostate cancer from 1997 through 2018. For patients with quiescent IBD at their cancer diagnosis, the primary outcome was relapse of IBD. For patients with active IBD at their cancer diagnosis, the primary outcome was IBD remission. RESULTS: Our analysis included 447 patients with IBD (44% with Crohn's disease, 53% with ulcerative colitis, and 3% with IBD unclassified) who had either breast (78%) or prostate (22%) cancer. At their cancer diagnosis, 400 patients (90%) had inactive IBD, and 47 (10%) had active IBD. Among patients with inactive IBD, 112 (28%) developed active IBD. Previous exposure to steroids, immunomodulators, or biologics was associated with IBD relapse after a cancer diagnosis (hazard ratio [HR] for steroids, 1.79; 95% CI, 1.18-2.71; HR for immunomodulators, 2.22; 95% CI, 1.38-3.55; HR for biologics, 1.95; 95% CI, 1.01-5.36). Hormone monotherapy (HR, 2.00; 95% CI, 1.21-3.29) and combination cytotoxic and hormone therapy (HR, 1.86; 95% CI, 1.01-3.43) was associated with IBD relapse. Among 34 patients who received only cytotoxic chemotherapy, 75% remained in remission from IBD at 250 months compared with 42% of those who received hormone monotherapy (log rank, 0.02). Among patients with active IBD at their cancer diagnosis, 14 (30%) entered remission from IBD, but there were no significant factors of achieving IBD remission. CONCLUSIONS: In a multicenter retrospective study, we found that patients with IBD and breast or prostate cancer who receive hormone therapy have an increased risk for relapse of IBD and related adverse outcomes.

Development and Validation of Clinical Scoring Tool to Predict Outcomes of Treatment With Vedolizumab in Patients With Ulcerative Colitis.

BACKGROUND & AIMS: We created and validated a clinical decision support tool (CDST) to predict outcomes of vedolizumab therapy for ulcerative colitis (UC). METHODS: We performed logistic regression analyses of data from the GEMINI 1 trial, from 620 patients with UC who received vedolizumab induction and maintenance therapy (derivation cohort), to identify factors associated with corticosteroid-free remission (full Mayo score of 2 or less, no subscore above 1). We used these factors to develop a model to predict outcomes of treatment, which we called the vedolizumab CDST. We evaluated the correlation between exposure and efficacy. We validated the CDST in using data from 199 patients treated with vedolizumab in routine practice in the United States from May 2014 through December 2017. RESULTS: Absence of exposure to a tumor necrosis factor (TNF) antagonist (+3 points), disease duration of 2 y or more (+3 points), baseline endoscopic activity (moderate vs severe) (+2 points), and baseline albumin concentration (+0.65 points per 1 g/L) were independently associated with corticosteroid-free remission during vedolizumab therapy. Patients in the derivation and validation cohorts were assigned to groups of low (CDST score, 26 points or less), intermediate (CDST score, 27-32 points), or high (CDST score, 33 points or more) probability of vedolizumab response. We observed a statistically significant linear relationship between probability group and efficacy (area under the receiver operating characteristic curve, 0.65), as well as drug exposure (P < .001) in the derivation cohort. In the validation cohort, a cutoff value of 26 points identified patients who did not respond to vedolizumab with high sensitivity (93%); only the low and intermediate probability groups benefited from reducing intervals of vedolizumab administration due to lack of response (P = .02). The vedolizumab CDST did not identify patients with corticosteroid-free remission during TNF antagonist therapy. CONCLUSIONS: We used data from a trial of patients with UC to develop a scoring system, called the CDST, which identified patients most likely to enter corticosteroid-free remission during vedolizumab therapy, but not anti-TNF therapy. We validated the vedolizumab CDST in a separate cohort of patients in clinical practice. The CDST identified patients most likely to benefited from reducing intervals of vedolizumab administration due to lack of initial response. ClinicalTrials.gov no: NCT00783718.

Transabdominal Pouch Salvage for Failed Minimally Invasive Versus Open IPAA: A Case-Matched Study.

BACKGROUND: Modality of index IPAA creation may affect the results after redo IPAA surgery for IPAA failure. To our knowledge, there is no study evaluating the effects of modality of index IPAA creation on redo IPAA outcomes. OBJECTIVE: This study aimed to compare short- and long-term outcomes of transabdominal redo IPAA surgery for failed minimally invasive IPAA and open IPAA. DESIGN: This was a retrospective cohort study. SETTINGS: This investigation was based on a single-surgeon experience on redo IPAA. PATIENTS: Patients undergoing transabdominal redo IPAA for a failed minimally invasive IPAA and open IPAA between September 2007 and September 2017 were included. MAIN OUTCOME MEASURES: Short-term complications and long-term outcomes were compared between 2 groups. RESULTS: A total of 42 patients with failed index minimally invasive IPAA were case matched with 42 failed index open IPAA counterparts. The interval between index IPAA and redo IPAA operations was shorter in patients who had minimally invasive IPAA (median, 28.5 vs 56.0 mo; p = 0.03). A long rectal stump (>2 cm) was more common after minimally invasive IPAA (26% vs 10%; p = 0.046). Redo IPAAs were constructed more commonly with staplers in the laparoscopy group compared with open counterparts (26% vs 10%; p = 0.046), and other intraoperative details were comparable. Although short-term morbidity was similar between 2 groups, abscess formation (7% vs 24%; p = 0.035) was more frequent in patients who had index IPAA with open technique. Functional outcomes were comparable. Redo IPAA survival for failed minimally invasive IPAA and open IPAA was comparable. LIMITATIONS: This study was limited by its retrospective, nonrandomized nature and relatively low patient number. CONCLUSIONS: A long rectal cuff after minimally invasive IPAA is a potential and preventable risk factor for failure. Due to its technical and patient-related complexity, handsewn anastomoses in redo IPAA are associated with increased risk of abscess formation. See Video Abstract at http://links.lww.com/DCR/B252. RESCATE DEL RESERVORIO ILEO-ANAL POR VIA TRANSABDOMINAL EN CASOS DE FUGA ANASTOMÓTICA ENTRE ABORDAGE MINIMAMENTE INVASIVO Y ABORDAJE ABIERTO: ESTUDIO DE EMPAREJAMIENTO DE MUESTRAS Y CASOS: La creación de modalidades e índices de Reservorios Ileo-Anales (RIA) pueden afectar los resultados después de rehacer la cirugía de RIAs por fallas en el reservorio. Hasta donde sabemos, no hay ningún estudio que evalúe los efectos de la modalidad de creación de índices RIA en los resultados para el rescate del reservorio.Este estudio tuvo como objetivo comparar los resultados a corto y largo plazo de la cirugía transabdominal redo RIA en casos de fracaso por via mínimamente invasiva (MI-RIA) o por la vía abierta (A-RIA).Estudio de cohortes tipo retrospectivo.Investigación basada en la experiencia de un solo cirujano en redo del Reservorio Ileo-Anal.Se incluyeron aquellos pacientes sometidos a re-operación transabdominal y re-confección de un RIA por fallas en el MI-RIA y en el A-RIA durante un lapso de tiempo entre septiembre 2007 y septiembre 2017.Las complicaciones a corto plazo y los resultados a largo plazo se compararon entre los dos grupos.Un total de 42 pacientes con índice fallido de MI-RIA fueron emparejados con 42 homólogos con índice fallido de A-RIA. El intervalo entre las operaciones de RIA y redo RIA fué más corto en pacientes que tenían MI-RIA (mediana, 28,5 meses frente a 56 meses, p = 0,03). Un muñón rectal largo (> 2 cm) fue más común después de MI-RIA (26% vs 10%, p = 0.046). Redo RIAs se construyeron más comúnmente con engrampadoras en el grupo Minimalmente Invasivo en comparación con la contraparte abiertas (26% vs 10%, p = 0.046). Aunque la morbilidad a corto plazo fue similar entre los dos grupos, la aparición de abscesos (7% frente a 24%, p = 0.035) fue más frecuente en pacientes que tenían RIA con técnica abierta. Los resultados funcionales fueron comparables. La sobrevida de las redo RIAs para MI-RIA y A-RIA fallidas, también fué comparable.Este estudio estuvo limitado por su naturaleza retrospectiva, no aleatoria y el número relativamente bajo de pacientes.Un muñon rectal largo después de MI-RIA es un factor de riesgo potencial y previsible para el fracaso. Debido a su complejidad técnica y relacionada con el paciente, las anastomosis suturadas a mano en redo RIA están asociadas con un mayor riesgo de formación de abscesos. Consulte Video Resumen en http://links.lww.com/DCR/B252.

First-Line Biologics or Small Molecules in Inflammatory Bowel Disease: a Practical Guide for the Clinician.

PURPOSE OF REVIEW: Treating moderate-to-severe inflammatory bowel disease has become increasingly complex as the array of available biologics increases. Moreover, tofacitinib, the first small molecule approved for IBD, is available for use in ulcerative colitis. Choosing the right biologic, for the right patient, at the right time, can be a confusing and daunting task for clinicians. RECENT FINDINGS: In this review, we summarize the evidence for first-line use of the available biologics by disease state. Special circumstances for consideration including rapidity of action, safety, comparative effectiveness, postoperative Crohn's disease, fertility and pregnancy, and extraintestinal manifestations are discussed. In the moderate-to-severe UC patient, vedolizumab and infliximab are preferred first-line options. In the moderate-to-severe CD patient with a penetrating phenotype or with multiple EIMs, infliximab or adalimumab are the preferred first-line agents. In the moderate-to-severe CD patient with an inflammatory phenotype, anti-TNF, vedolizumab, and ustekinumab are all reasonable options.

Alvimopan for the Prevention of Postoperative Ileus in Inflammatory Bowel Disease Patients.

BACKGROUND: Postoperative ileus (POI) is a temporary delay of coordinated intestinal peristalsis. Alvimopan, an oral peripherally acting mu-opioid receptor antagonist approved for accelerating gastrointestinal recovery, has never been studied specifically in patients with inflammatory bowel disease (IBD). AIM: To investigate the efficacy of alvimopan in preventing POI among IBD patients. METHODS: A retrospective chart review was conducted on 246 IBD patients undergoing bowel surgery between 2012 and 2017. Data collected included demographics, IBD subtype, length of stay (LOS), postoperative gastrointestinal symptoms, and administration of alvimopan. The primary outcome was POI; secondary gastrointestinal recovery outcomes were: time to first flatus, time to first bowel movement, time to tolerating a liquid diet, time to tolerating solid food, and LOS. RESULTS: When compared with the control group, patients in the alvimopan group had shorter times to tolerating liquids and solids, first flatus, and first bowel movements (p < 0.01). LOS was shorter in the alvimopan group when compared with controls (p < 0.01). The overall incidence of POI was higher in controls than in the alvimopan group (p = 0.07). For laparoscopic surgeries, the incidence of POI was also higher in controls than in the alvimopan group (p < 0.01). On multivariable analysis, alvimopan significantly decreased time to all gastrointestinal recovery endpoints when compared to controls (p < 0.01). CONCLUSIONS: Alvimopan is effective in accelerating time to gastrointestinal recovery and reducing POI in IBD patients. While the benefits of alvimopan have been demonstrated previously, this is the first study of the efficacy of alvimopan in IBD patients.

Novel Dual-Energy Computed Tomography Enterography Iodine Density Maps Provide Unique Depiction of Crohn Disease Activity.

OBJECTIVE: To create a map of iodine densities within affected segments of small-bowel Crohn disease (CD) derived from contrast-enhanced dual-energy computed tomography enterography (DECTE) studies. METHODS: Twenty CD patients imaged with intravenous contrast-enhanced DECTE between June 2016 and December 2017 were retrospectively identified. Ten patients without clinical evidence of CD and 8 normal-appearing jejunal segments in CD patients were controls. Using prototype software, 8 manual contours were drawn along the mucosa of affected segments. Relatively normal-appearing bowel was included at the edges. These contours served as a basis for iodine density calculation and 3-dimensional iodine density map rendering. Color-coded iodine densities allowed detection and quantification of the most and least dense portion of each segment and also permitted relative comparison between segments. RESULTS: The average iodine density per CD involved segment ranged 1.0 to 3.3 mg/mL, which differed significantly from normal ileum (P < 0.0001) and normal-appearing jejunum in patients with CD (P = 0.0009). Standard deviations ranged from 0.8 to 1.7 mg/mL, which differed significantly from normal ileum (P = 0.0039) and normal-appearing jejunum in patients with CD (P = 0.0056). The amplitude of the power spectrum ranged from 0.66 to 3.3 demonstrating patches of iodine rather than uniform distribution. This differed significantly from normal ileum (P = 0.0005) and normal-appearing jejunum in patients with CD (P = 0.0004). CONCLUSIONS: Heterogeneous CD activity and distribution can be displayed as iodine density maps created from DECTE.

Crohn's Disease Activity Quantified by Iodine Density Obtained From Dual-Energy Computed Tomography Enterography.

OBJECTIVE: The objective of this study was to assess if bowel wall iodine density obtained from dual-source, dual-energy computed tomography enterography (DECTE) could be a biomarker of Crohn's disease activity. METHODS: Twenty-two patients with Crohn's disease imaged with DECTE from February 2016 to May 2018 were retrospectively identified by departmental report search. Iodine maps were created with commercial software (Syngovia). Iodine content was normalized to the aorta, and then manual dual-energy region-of-interest cursors were placed over the visibly assessed maximal and minimal iodine density within segments of involved as well as unaffected small bowel. The mixed Hounsfield unit value, maximum iodine density (Imax), and minimum iodine density (Imin) were recorded. The length of affected bowel demonstrating maximum disease activity as a percentage of overall involvement was subjectively assessed. A weighted iodine density (Iweighted) was calculated. The clinical assessment of disease activity using erythrocyte sedimentation rate, C-reactive protein, fecal calprotectin, colonoscopy/endoscopy, and surgery, if available, served as the reference standard. The Crohn's disease activity index was also used as a separate additional reference standard. RESULTS: Significant heterogeneity within the affected segments was present. The average Imax and Imin of affected bowel was 4.27 ± 1.11 (2.4-7.4) mg/mL and 2.71 ± 0.51 (2.2-3.9) mg/mL, respectively. Iodine density of normal-appearing small bowel was 1.40 ± 0.26 (0.9-1.9) mg/mL. The Imax and Imin of affected bowel differed significantly from normal bowel (P < 0.0001). Mixed Hounsfield unit (101.82 ± 27.5) also statistically differed (46.33 ± 19.62) (P < 0.0001). Using overall clinical assessment as the reference standard, all patients with Imin of greater than 2.6 mg/mL, Iweighted of greater than 3.3 mg/mL, or Imax of greater than 4.7 mg/mL had clinically active disease. Sixteen of 17 patients with Imin of greater than 2.2 mg/mL and 14/15 with Iweighted of greater than 3 mg/mL had clinically active disease. Using Crohn's disease activity index as the reference standard, all patients with Imin of greater than 2.7 mg/mL, Iweighted of greater than 3.6 mg/mL, or Imax of greater than 5.4 mg/mL had clinically active disease. The median effective dose was 4.64 ± 1.68 mSv (range, 2.03-8.12 mSv). CONCLUSIONS: Iodine density obtained from DECTE highlights regions of maximal activity within affected bowel segments. An iodine density of 2 mg/mL appears to be a threshold between normal bowel segments and those with active Crohn's disease. Iodine density measurement thresholds Imin of greater than 2.6 mg/mL, Iweighted of greater than 3.3 mg/mL, and Imax of greater than 4.7 mg/mL correlate with established clinical markers of disease activity, with Imin seemingly most useful in daily clinical practice.

Retrospective Analysis of Safety of Vedolizumab in Patients With Inflammatory Bowel Diseases.

BACKGROUND & AIMS: There are few real-world data on the safety of vedolizumab for treatment of Crohn's disease (CD) or ulcerative colitis (UC). We quantified rates and identified factors significantly associated with infectious and non-infectious adverse events in clinical practice. METHODS: We performed a retrospective review of data from a multicenter consortium database (from May 2014 through June 2017). Infectious and non-infectious adverse events were defined as those requiring antibiotics, hospitalization, vedolizumab discontinuation, or resulting in death. Rates were quantified as proportions and events per 100 patient years of exposure (PYE) or follow up (PYF). We performed multivariable logistic regression analyses to identify factors significantly associated with events and reported as odds ratios (OR) with 95% CIs. RESULTS: Our analysis comprised 1087 patients (650 with CD and 437 with UC; 55% female; median age, 37 years) with 861 PYE and 955 PYF. Infections were observed in 68 patients (6.3%; 7.9 per 100 PYE, 7.1 per 100 PYF); gastrointestinal infections (n = 31, 2.4 per 100 PYE, 2.2 per 100 PYF) and respiratory infections (n = 14, 1.6 per 100 PYE, 1.5 per 100 PYF) were the most common. Arthralgias were the most common non-infectious adverse events (n = 31, 2.9%; 3.6 per 100 PYE). Two patients developed malignancies (squamous cell skin cancer and colorectal cancer; 0.23 per 100 PYE, 0.21 per 100 PYF). Active smoker status (OR, 3.39) and number of concomitant immunosuppressive agents (corticosteroids or immunomodulators; OR, 1.72 per agent) used were independently associated with infections. CONCLUSION: In a retrospective cohort study of patients with IBD, we found vedolizumab to be well tolerated with an overall favorable safety profile. Active smoking and concomitant use of immunosuppressive agents were independently associated with infections.