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.

Reactive Immunomodulator Addition to Infliximab Monotherapy Restores Clinical Response in Inflammatory Bowel Disease: A Meta-Analysis.

BACKGROUND AND AIMS: Patients with inflammatory bowel disease (IBD) receiving infliximab (IFX) commonly experience immunogenic loss of response (LOR) by formation of anti-drug antibodies (ADAs). An immunomodulator (IMM) used in combination with initial IFX induction is known to reduce ADA development and improve clinical outcomes. We aimed to assess the impact of reactively adding an IMM to patients on IFX monotherapy. METHODS: We conducted a retrospective cohort study and systematic review with meta-analysis of patients with IBD demonstrating immunologic LOR, with or without clinical LOR, that had an IMM (azathioprine, 6-mercaptopurine, or methotrexate) reactively added (reactive combination therapy; rCT) to combat elevated ADAs and raise IFX level. Data were extracted for pooled effect size estimation using random-effects models, and ADA and IFX trough levels were compared pre- and post-IMM initiation. RESULTS: We identified 6 patients who received rCT due to rising ADA titers and low IFX levels. Median ADA titer decreased from 506 ng/mL (interquartile range (IQR) [416-750]) to 76.5 ng/mL (IQR [25.8-232]), an 85% decrease (p = 0.031). Median IFX trough increased from 0.4 µg/mL (IQR [0.4-0.48]) to 8.25 µg/mL (IQR [3.7-9.6]), a 20.6-fold increase (p = 0.038). Meta-analysis pooled effect size of 7 studies with 89 patients showed an 87% ADA titer reduction [95% confidence interval (CI) = 72-94%], 6.7-fold increased IFX trough (95% CI = 2.4-18.7), and 76% clinical remission rescue rate (95% CI = 59-93%). CONCLUSIONS: These results suggest rCT is a valid rescue strategy in patients with immunogenic LOR to IFX to reduce ADA titers, restore therapeutic IFX levels, and recapture clinical remission of IBD.

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.

Inflammatory bowel disease and cannabis: key counseling strategies.

PURPOSE OF REVIEW: Cannabis use is becoming more frequent in patients with inflammatory bowel disease (IBD). Because of the increased usage, gastroenterologists need to be cognizant of the benefits and risks associated with cannabis use in the IBD-patient population. RECENT FINDINGS: Recent studies have attempted to determine whether cannabis can improve biomarkers or endoscopic findings of inflammation in patients with IBD, but the results have been inconclusive. However, cannabis has been shown to have an impact on the symptoms and quality of life of individuals with IBD. Despite these benefits, the use of cannabis in IBD is not without risks, including the potential for systemic illness, toxin ingestion and significant drug interactions. SUMMARY: In this review article, we use a case-based approach to discuss the critical clinical data that informs us of the benefits and risks of cannabis use in IBD. The endocannabinoid system plays a crucial role in regulating various physiological functions including the gastrointestinal tract. Studies have investigated the impact of cannabis on various medical conditions, including IBD. Clinicians must be aware of the most recent data to properly educate their patients on the benefits and risks of its use.

The overall quality of evidence of recommendations surrounding nutrition and diet in inflammatory bowel disease.

BACKGROUND AND AIM: Recently, there has been an increased focus on the role nutrition and diet play in maintaining health in inflammatory bowel disease (IBD). We aimed to assess the overall quality, strength, and transparency of conflicts among guidelines on nutrition/diet in IBD. METHODS: A systematic search was performed on multiple databases from inception until January 1, 2021, to identify guidelines pertaining to nutrition or diet in IBD. All guidelines were reviewed for disclosure of conflicts of interest (COI) and funding, recommendation quality and strength, external document review, patient representation, and plans for update-as per Institute of Medicine (IOM) standards. In addition, recommendations and their quality were compared between guidelines/societies.​ RESULTS: Seventeen distinct societies and a total of 228 recommendations were included. Not all guidelines provided recommendations on key aspects of diet-such as the role of supplements or the appropriate micro/macro nutrition in IBD. Fifty-nine percent of guidelines reported on COI, 24% underwent external review, and 41% included patient representation. 18.4%, 25.9%, and 55.7% of recommendations were based on high-, moderate-, and low-quality evidence, respectively. 10.5%, 24.6%, and 64.9% of recommendations were strong, weak/conditional, and did not provide a strength, respectively. The proportion of high-quality evidence (p = 0.12) and strong recommendations (p = 0.83) did not significantly differ across societies. CONCLUSIONS: Many guidelines do not provide recommendations on key aspects of diet/nutrition in IBD. As over 50% of recommendations are based on low-quality evidence, further studies on nutrition/diet in IBD are warranted to improve the overall quality of evidence.

Patient adverse events and technical failures with the bravo capsule pH system: insights from the MAUDE database.

BACKGROUND: The BRAVO pH monitor system can benefit patients with ongoing GERD symptoms despite treatment and/or atypical symptoms. We aim to investigate the number and type of complications associated with the BRAVO pH capsule. METHODS: From April 2016 through February 2021, we analyzed post-marketing surveillance data from the FDA Manufacturer and User Facility Device Experience (MAUDE) database. RESULTS: During the study period, approximately 1,651 reports were identified with 2391 cases associated with a device failure, and 254 reporting a patient-related adverse event. Most device complications were due to aspiration n = 153), followed by reported pain (n = 79), injury (unspecified) (n = 63), and additional radiologic imaging (n = 44). Laceration and bleeding accounted for 29 and 19 cases. Furthermore, three patients suffered perforation. Most device failures were due to loss or failure of the Bravo capsule to bond or adhere to the esophageal mucosa as planned (n = 1269), followed by an activation or positioning failure (n = 972), premature detachment of device (n = 284), and failure of the device to record or transmit data (n = 158). CONCLUSIONS: Findings from the MAUDE database highlight the risk of aspiration, hemorrhage/bleeding, perforation, injury, and retention as potential complications of BRAVO capsule placement.

A Randomized Trial Comparing the Specific Carbohydrate Diet to a Mediterranean Diet in Adults With Crohn's Disease.

BACKGROUND & AIMS: This study compared the effectiveness of the Specific Carbohydrate Diet (SCD) to the Mediterranean diet (MD) as treatment for Crohn's disease (CD) with mild to moderate symptoms. METHODS: Adult patients with CD and with mild-to-moderate symptoms were randomly assigned 1:1 to consume the MD or SCD for 12 weeks. For the first 6 weeks, participants received prepared meals and snacks according to their assigned diet. After 6 weeks, participants were instructed to follow the diet independently. The primary outcome was symptomatic remission at week 6. Key secondary outcomes at week 6 included fecal calprotectin (FC) response (FC <250 µg/g and reduction by >50% among those with baseline FC >250 µg/g) and C-reactive protein (CRP) response (high-sensitivity CRP <5 mg/L and >50% reduction from baseline among those with high-sensitivity CRP >5 mg/L). RESULTS: The study randomized 194 patients, and 191 were included in the efficacy analyses. The percentage of participants who achieved symptomatic remission at week 6 was not superior with the SCD (SCD, 46.5%; MD, 43.5%; P = .77). FC response was achieved in 8 of 23 participants (34.8%) with the SCD and in 4 of 13 participants (30.8%) with the MD (P = .83). CRP response was achieved in 2 of 37 participants (5.4%) with the SCD and in 1 of 28 participants (3.6%) with the MD (P = .68). CONCLUSIONS: The SCD was not superior to the MD to achieve symptomatic remission, FC response, and CRP response. CRP response was uncommon. Given these results, the greater ease of following the MD and other health benefits associated with the MD, the MD may be preferred to the SCD for most patients with CD with mild to moderate symptoms. ClinicalTrials.gov Identifier: NCT03058679.

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.

Endoscopic Disease Activity and Biologic Therapy Are Independent Predictors of Suboptimal Bowel Preparation in Patients with Inflammatory Bowel Disease Undergoing Colonoscopy.

BACKGROUND AND AIMS: Optimal bowel preparation (BP) is critical for endoscopic assessment of inflammation and dysplasia in patients with inflammatory bowel disease (IBD). Comorbidities and patient-related factors have been associated with suboptimal BP (SOBP) in the general population. We sought to identify disease-specific characteristics that may impact the quality of BP in patients with IBD. METHODS: We conducted a retrospective analysis of adult IBD patients who underwent outpatient colonoscopies between January 2014 and September 2020 at a large academic medical center. Quality of BP was documented using the Boston Bowel Preparation Scale (BBPS) or the Aronchick scale and dichotomized into "suboptimal" (BBPS 0-5 or Aronchick "fair," "poor," unsatisfactory") and "optimal" (BBPS 6-9 or Aronchick "excellent," "good"). IBD-specific and other factors associated with SOBP were evaluated using logistic regression analyses. RESULTS: Among a total of 395 IBD patients [54% males, mean age 40 years, 63% with Crohn's disease (CD), 35% with ulcerative colitis (UC)], 24.8% had SOBP. On multivariable analysis, moderate-to-severe endoscopic disease vs mild or inactive disease was associated with a higher odds of SOBP [adjusted OR 2.7(95% CI 1.52-4.94)], whereas baseline biologic use was associated with a lower odds of SOBP [aOR 0.24(0.09-0.65)] among the overall IBD cohort. Additionally, age > 65 years [aOR 2.99(1.19-7.54)] and single-dose vs split-dose BP [aOR 2.37(1.43-3.95)] were predictors of SOBP. In the subgroup analysis by IBD type, moderate-to-severe endoscopic disease predicted SOBP among both CD and UC cohorts. CONCLUSION: Endoscopic disease activity was predictive of SOBP, and biologic therapy was protective against SOBP among IBD patients.

Safety of biologics in inflammatory bowel disease patients with COVID-19.

BACKGROUND: Patients with Inflammatory bowel disease (IBD) remain highly concerned that either their disease or medications-namely, biologics-may increase the risk of severe coronavirus-2019 (COVID-19). We aimed to assess the safety of biologics in Inflammatory bowel disease (IBD) patients with COVID-19. METHODS: We systematically reviewed multiple databases to find relevant articles reporting the effect of biologics on "severe" COVID-19 in IBD patients. Those in the form of case series (> 10 patients), case-control, and cohort studies were included. Severe COVID-19 was defined as intensive care unit (ICU) admission, mechanical ventilation, and/or mortality. Pooled analysis with multivariate regression was performed. RESULTS: A total of 12 studies with 2681 patients were included. The proportion of females was (48.3%, 95% confidence interval (CI) 47.0-49.5%). The proportion of UC patients was (44.8%, 95% CI 41.0-48.5%). Overall, in IBD patients, the need for mechanical ventilation, intensive care unit (ICU) admission, and mortality was 5.1%, 6.1%, and 4.5%, respectively. Use of biologics did not show a moderating effect on mechanical ventilation (p = 0.68), ICU admission (p = 0.27), or mortality (p = 0.20). CONCLUSIONS: Our findings advocate for the continued biologic therapy in IBD patients during the COVID-19 pandemic. Nevertheless, the incidence, severity, and outcomes related to COVID-19 in IBD patients' needs to be reassessed as data continues to emerge.

Impact of inflammatory bowel disease on hospital outcomes in acute ischemic stroke: a nationwide cohort study.

PURPOSE: Patients with inflammatory bowel disease (IBD) have an increased risk of venous thrombotic events. The impact IBD has on arterial thrombosis is not well characterized. We aimed to identify the impact of IBD on hospital outcomes in patients admitted for acute ischemic stroke (AIS). METHODS: This is a retrospective cohort study utilizing the 2017 National Inpatient Sample. We identified all adult patients with a principal diagnosis of AIS and compared those with a concurrent diagnosis of IBD to those without-subgrouped by ulcerative colitis (UC) and Crohn's disease (CD). Outcomes were mortality and healthcare usage among IBD patients with AIS. Multivariate analysis was used to control for confounders. Analyses were performed using STATA. RESULTS: Five hundred twenty-four thousand and forty-five patients were admitted for AIS in 2017; of them 2200 (0.41%) had a concurrent diagnosis of IBD. The presence of IBD did not significantly affect in-hospital mortality (4.09% vs. 4.01%) among patients admitted for AIS [OR 1.07 95% CI: 0.65-1.76], with similar findings upon subgroup analysis of UC [OR 0.91, 95% CI: 0.39-2.09] and CD [OR 1.17, 95% CI: 0.62-2.19]. Mean hospital length of stay and charges/costs in AIS were similar irrespective of IBD. CONCLUSIONS: UC and CD do not appear to be associated with a higher risk of mortality or increased healthcare usage in AIS. AIS risk assessment in patients with IBD is important but should be done in a similar fashion to the general population.

Role of Hospital Teaching Status on Outcomes of Patients with Inflammatory Bowel Disease: A Nationwide Analysis.

BACKGROUND: Data regarding hospitalization outcomes in patients with inflammatory bowel disease (IBD) with respect to hospital teaching status are largely unknown. AIMS: We aimed to investigate the impact of hospital teaching status on IBD hospitalization outcomes. METHODS: In this retrospective analysis, we queried the 2016 and 2017 National Inpatient Sample (NIS) databases using the International Classification of Diseases 10th revision (ICD-10) coding system. All adult patients with a principal diagnosis of IBD were included. We stratified the IBD group into ulcerative colitis (UC), Crohn's disease (CD), and complicated IBD. Our primary outcome was mortality. Statistical analysis was performed using STATA, version 16.0. RESULTS: Of the 189,950 adult patients with IBD, the majority were admitted to teaching hospitals (70.9%). There was no significant difference in mortality based upon hospital teaching status (aOR 1.18, p = 0.48); however, these patients had an increased mean length of stay (adjusted coefficient: 0.82, p < 0.01), charges (adjusted coefficient: $8732, p < 0.01), and costs ($2871, p < 0.01). On subgroup analysis, patients with UC admitted to teaching hospitals had a significantly increased in-hospital mortality (aOR 2.11, p < 0.05), while those admitted with CD did not (aOR 0.80, p = 0.4). Among patients with complicated IBD, 73.17% were admitted to teaching hospitals, and no significant difference in in-hospital mortality was seen (aOR 1.06, p = 0.8). CONCLUSION: While outcome differences are likely related to multiple unaccounted factors, greater efforts should be placed to cost-effectively manage patients with IBD at teaching institutions. Future studies are warranted to fully comprehend these variations.

Donning a New Approach to the Practice of Gastroenterology: Perspectives From the COVID-19 Pandemic Epicenter.

The COVID-19 pandemic seemingly is peaking now in New York City and has triggered significant changes to the standard management of gastrointestinal diseases. Priorities such as minimizing viral transmission, preserving personal protective equipment, and freeing hospital beds have driven unconventional approaches to managing gastroenterology (GI) patients. Conversion of endoscopy units to COVID units and redeployment of GI fellows and faculty has profoundly changed the profile of most GI services. Meanwhile, consult and procedural volumes have been reduced drastically. In this review, we share our collective experiences regarding how we have changed our practice of medicine in response to the COVID surge. Although we review our management of specific consults and conditions, the overarching theme focuses primarily on noninvasive measures and maximizing medical therapies. Endoscopic procedures have been reserved for those timely interventions that are most likely to be therapeutic. The role of multidisciplinary discussion, although always important, now has become critical. The support of our faculty and trainees remains essential. Local leadership can encourage well-being by frequent team check-ins and by fostering trainee development through remote learning. Advancing a clear vision and a transparent process for how to organize and triage care in the recovery phase will allow for a smooth transition to our new normal.

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.

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.

Shorter Disease Duration Is Associated With Higher Rates of Response to Vedolizumab in Patients With Crohn's Disease But Not Ulcerative Colitis.

BACKGROUND & AIMS: Patients with Crohn's disease (CD), but not ulcerative colitis (UC), of shorter duration have higher rates of response to tumor necrosis factor (TNF) antagonists than patients with longer disease duration. Little is known about the association between disease duration and response to other biologic agents. We aimed to evaluate response of patients with CD or UC to vedolizumab, stratified by disease duration. METHODS: We analyzed data from a retrospective, multicenter, consortium of patients with CD (n = 650) or UC (n = 437) treated with vedolizumab from May 2014 through December 2016. Using time to event analyses, we compared rates of clinical remission, corticosteroid-free remission (CSFR), and endoscopic remission between patients with early-stage (≤2 years duration) and later-stage (>2 years) CD or UC. We used Cox proportional hazards models to identify factors associated with outcomes. RESULTS: Within 6 months initiation of treatment with vedolizumab, significantly higher proportions of patients with early-stage CD, vs later-stage CD, achieved clinical remission (38% vs 23%), CSFR (43% vs 14%), and endoscopic remission (29% vs 13%) (P < .05 for all comparisons). After adjusting for disease-related factors including previous exposure to TNF antagonists, patients with early-stage CD were significantly more likely than patients with later-stage CD to achieve clinical remission (adjusted hazard ratio [aHR], 1.59; 95% CI, 1.02-2.49), CSFR (aHR, 3.39; 95% CI, 1.66-6.92), and endoscopic remission (aHR, 1.90; 95% CI, 1.06-3.39). In contrast, disease duration was not a significant predictor of response among patients with UC. CONCLUSIONS: Patients with CD for 2 years or less are significantly more likely to achieve a complete response, CSFR, or endoscopic response to vedolizumab than patients with longer disease duration. Disease duration does not associate with response vedolizumab in patients with UC.

Development and Validation of a Scoring System to Predict Outcomes of Vedolizumab Treatment in Patients With Crohn's Disease.

BACKGROUND & AIMS: As more treatment options for inflammatory bowel diseases become available, it is important to identify patients most likely to respond to different therapies. We created and validated a scoring system to identify patients with Crohn's disease (CD) who respond to vedolizumab. METHODS: We collected data from the GEMINI 2 phase 3 trial of patients with active CD treated with vedolizumab for 26 weeks (n = 814) and performed logistic regression analysis to identify factors associated with clinical, steroid-free, and durable remission (derivation set). We used these data to develop a clinical decision support tool, which we validated using data from 366 participants in a separate clinical practice observational cohort of patients with active CD treated with vedolizumab for 26 weeks (the VICTORY cohort). We evaluated the ability of this tool to identify patients in clinical remission or corticosteroid-free remission, or those with mucosal healing (MH), clinical remission with MH, or corticosteroid-free remission with MH after vedolizumab therapy using receiver operating characteristic area under the curve (AUC) analyses. The primary outcome was to develop and validate a list of factors associated with achieving remission by vedolizumab in patients with active CD. RESULTS: In the derivation analysis, we identified absence of previous treatment with a tumor necrosis factor antagonist (+3 points), absence of prior bowel surgery (+2 points), absence of prior fistulizing disease (+2 points), baseline level of albumin (+0.4 points per g/L), and baseline concentration of C-reactive protein (reduction of 0.5 points for values between 3.0 and 10.0 mg/L and 3.0 points for values >10.0 mg/L) as factors associated with remission. In the validation set, our model identified patients in clinical remission with an AUC of 0.67, patients in corticosteroid-free remission with an AUC of 0.66, patients with MH with an AUC of 0.72, patients in clinical remission with MH with an AUC of 0.73, and patients in corticosteroid-free clinical remission with MH with an AUC of 0.75. A cutoff value of 13 points identified patients in clinical remission after vedolizumab therapy with 92% sensitivity, patients in corticosteroid-free remission with 94% sensitivity, patients with MH with 98% sensitivity, patients with clinical remission and MH with 100% sensitivity, and patients with corticosteroid-free clinical remission with MH with 100% sensitivity. CONCLUSIONS: We developed and validated a scoring system to identify patients with CD most likely to respond to 26 weeks of vedolizumab therapy. Further studies are needed to optimize its accuracy in select populations and determine its cost-effectiveness.

Mortality Risk of Inflammatory Bowel Disease: A Case-Control Study of New York State Death Records.

BACKGROUND: Studies examining the mortality risk of inflammatory bowel disease (IBD) have yielded conflicting results, and most do not account for recent advancements made in the treatment of Crohn's disease (CD) and ulcerative colitis (UC). We aim to assess the overall, premature, and cause-specific mortality in IBD patients over a 17-year time period and to evaluate any differences since the introduction of biologic therapy. METHODS: A death record case-control study was performed to explore the odds of premature death (before age 65) and all-cause mortality among those with IBD. Cases consisted of IBD patients (1,129 with CD and 841 with UC) who died in New York State (NYS) from 1993 to 2010. Controls (n = 7880) were matched 4:1 on the basis of sex and zip code from those who died in NYS in the same time frame, without an IBD diagnosis. RESULTS: Compared with matched controls, those with CD (OR 1.56, CI 95% 1.34-1.82), but not UC (OR 0.72, CI 95% 0.59-0.89), were more likely to die prematurely. Both those with UC and CD were more likely to die from a gastrointestinal cause (CD OR 15.28, 95% CI 12.11-19.27; UC OR 14.02, 95% CI 10.76-18.26). There was no difference in the cause or age of death before and after the introduction of anti-TNF agents in those with IBD. CONCLUSIONS: Both CD and UC cases were more likely to die of a gastrointestinal etiology, and CD patients were more likely to die prematurely. There was no significant difference in the premature death, average age of death, and cause of death in this IBD population after the availability of anti-TNF therapy.

Correction: Vedolizumab for Ulcerative Colitis: Treatment Outcomes from the VICTORY Consortium.

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