Faculty Bibliography

BACKGROUND:There is little data regarding the risk of new or recurrent cancer in patients with inflammatory bowel disease (IBD) and a prior history of cancer who are exposed to ustekinumab or vedolizumab. We assessed the risk of subsequent cancer in patients exposed to these agents. METHODS:We performed a retrospective cohort study of patients with IBD and a history of cancer at an academic medical center between January 2013 and December 2020. We collected data on demographics, IBD and cancer disease characteristics, and drug exposures. The primary exposure was immunosuppressive therapy after diagnosis of cancer. The primary outcome was interval development of new or recurrent cancer. RESULTS:Of 390 patients with IBD and a previous history of cancer, 37 were exposed to vedolizumab, 14 ustekinumab, 41 antitumor necrosis factor (anti-TNF), and 31 immunomodulator; and 267 were not exposed to immunosuppression following cancer diagnosis. During a total median follow-up time of 52 months, 81 (20%) patients developed subsequent cancer: 6 (16%) were exposed to vedolizumab, 2 (14%) to ustekinumab, 3 (10%) to immunomodulators, 12 (29%) to anti-TNF, and 56 (21%) with no immunosuppression (P = .41). In a multivariable Cox model adjusting for age, IBD subtype, smoking, cancer recurrence risk, and cancer stage, there was no increase in subsequent cancer with vedolizumab (adjusted hazard ratio, 1.36; 95% CI, 0.27-7.01) or ustekinumab (adjusted hazard ratio, 0.96; 95% CI, 0.17-5.41). Patients with more than 1 biologic exposure also did not have an increased risk of subsequent cancer. CONCLUSIONS:Exposure to ustekinumab or vedolizumab in patients with IBD and a prior history of cancer does not appear to be associated with an increased risk of subsequent new or recurrent cancer.

Background. The phase 3 True North (TN) study demonstrated the efficacy and safety of oral ozanimod 0.92 mg once daily (equivalent to ozanimod HCl 1 mg) in patients with moderately to severely active ulcerative colitis (UC). The ongoing TN open-label extension (OLE) study is exploring longer-term efficacy and safety of ozanimod in the treatment of UC. This interim analysis of the TN OLE evaluated the efficacy and safety of ozanimod in patients who received 98 weeks of continuous ozanimod treatment.
Method(s): Patients in clinical response after 52 weeks of continuous ozanimod therapy during TN who rolled over into the OLE were included (data cutoff: September 30, 2020). Endoscopy was performed annually throughout the OLE and was scored by Mayo endoscopic score. Efficacy data (clinical remission, clinical response, endoscopic improvement, and corticosteroid-free remission) were analyzed using observed cases (OC) and nonresponder imputation (NRI). Safety data were also recorded.
Result(s): Of 131 patients in clinical response at TN Week 52, 83 (63%) were in clinical remission and 48 (37%) were in clinical response only (but not clinical remission) upon entry to the OLE. Nearly 73% of the overall population of clinical responders, including 69% of patients who achieved clinical remission and 79% of patients who achieved clinical response only, completed Week 46 of the OLE (ie, Week 98 of continuous ozanimod therapy) at the time of data cutoff when outcomes were measured (NRI group). Baseline demographic and clinical characteristics were similar for patients in clinical remission and in clinical response only, except more patients with clinical response only at OLE entry were exposed to prior immunomodulators or tumor necrosis factor inhibitors at TN baseline. A high proportion of the overall population sustained clinical remission (67%), clinical response (97%), endoscopic improvement (74%), and corticosteroid-free remission (63%) on ozanimod at OLE Week 46 (OC analysis); NRI values were 44%, 64%, 58%, and 42%, respectively. There were higher rates of clinical remission (73% vs 55%), endoscopic improvement (82% vs 58%), and corticosteroid-free remission (71% vs 50%) among patients entering the OLE in clinical remission versus clinical response only (OC analysis). In the overall population of clinical responders, the mean partial Mayo score stabilized by Week 18 (mean, 1.3 points; range, 0-6 points) of the maintenance period and was maintained through OLE Week 46 (mean, 0.9 points; range, 0-4 points) in patients treated with continuous ozanimod. No new safety findings emerged from this extended analysis; 1 sudden death occurred during the OLE and was determined to be unrelated to ozanimod. Conclusion(s): This interim analysis of the TN OLE found that patients who achieved clinical response or clinical remission after 52 weeks of ozanimod had a high rate of sustaining clinical response, clinical remission, and endoscopic improvement for another year with continued use of ozanimod. Patients who were in clinical response after 52 weeks of ozanimod could achieve clinical remission with continued ozanimod therapy. No additional safety signals were observed

BACKGROUND:Venous thromboembolism (VTE) is a significant cause of morbidity and mortality among patients with inflammatory bowel disease (IBD). However, data on national trends remain limited. AIMS/OBJECTIVE:To assess national trends in VTE-associated hospitalisations among patients with IBD as well as risk factors for, and mortality associated with, these events METHODS: Using the U.S. Nationwide Inpatient Sample from 2000-2018, temporal trends in VTE were assessed using the National Cancer Institute's Joinpoint Regression Program with estimates presented as the average annual percent change (AAPC) with 95% confidence intervals (CIs). RESULTS:Between 2000 and 2018, there were 4,859,728 hospitalisations among patients with IBD, with 128,236 (2.6%) having a VTE, and 6352 associated deaths. The rate of VTE among hospitalised patients with IBD increased from 192 to 295 cases per 10,000 hospitalisations (AAPC 2.4%, 95%CI 1.4%, 3.4%, p < 0.001), and remained significant when stratified by ulcerative colitis (UC) and Crohn's disease as well as by deep vein thrombosis and pulmonary embolism. On multivariable analysis, increasing age, male sex, UC (aOR: 1.30, 95%CI 1.26, 1.33), identifying as non-Hispanic Black, and chronic corticosteroid use (aOR: 1.22, 95%CI 1.16, 1.29) were associated with an increased risk of a VTE-associated hospitalisation. CONCLUSION/CONCLUSIONS:Rates of VTE-associated hospitalisations are increasing among patients with IBD. Continued efforts need to be placed on education and risk reduction.

Introduction: Ozanimod, an oral sphingosine 1-phosphate (S1P) receptor modulator selectively targeting S1P1 and S1P5, is approved in the US and Europe for the treatment of moderately to severely active ulcerative colitis (UC) in adults. In the phase 3, randomized, double-blind, placebocontrolled True North study (NCT02435992), ozanimod led to statistically significant improvements in clinical, endoscopic, and histologic outcomes at Weeks 10 and 52 compared to placebo in patients with moderately to severely active UC. Aims & Methods: The aims of this analysis were to describe the characteristics of patients who did not achieve clinical response at Week 10 of ozanimod induction in True North, and to determine the proportion of patients who benefited from additional ozanimod treatment. In True North, patients were randomized 2:1 to receive double-blind ozanimod 0.92 mg (equivalent to ozanimod HCl 1 mg) or placebo (Cohort 1) or open-label ozanimod 0.92 mg (Cohort 2). Those who did not have clinical response at Week 10 were eligible to receive ozanimod in an open-label extension (OLE). This analysis examined patients in Cohort 1 who were treated with double-blind ozanimod but did not achieve clinical response at Week 10 and subsequently continued ozanimod in the OLE (n=150). Demographics and disease characteristics were assessed at induction baseline, and disease activity was assessed at induction baseline and Week 10 (baseline for OLE entry). Symptomatic clinical response, defined as a reduction from induction baseline in the partial Mayo score of >=1 point and >=30% with at least 1 point decrease in rectal bleeding subscore (RBS) or absolute RBS <=1, during the OLE was determined using nonresponder imputation.
Result(s): A total of 150 patients who received ozanimod in Cohort 1 did not achieve clinical response at Week 10 of the induction period and entered the OLE. These patients had a mean age of 38.6 years, 66.0% were men, 44.0% had extensive disease, and the mean total Mayo score at baseline was 9.2 points. Despite not achieving clinical response at Week 10, these patients had a mean total Mayo score that improved from 9.2 at baseline to 8.5 at Week 10, with a larger percentage of patients having an RBS of 0 at Week 10 (23.3%; 35/150) than at baseline (0.7%; 1/150). Almost half of the patients who did not achieve clinical response at Week 10 had symptomatic clinical response at OLE Week 10 (48.7%; 73/150), with 44% (66/150) achieving symptomatic clinical response at OLE Week 5.
Conclusion(s): This analysis of the True North OLE found that approximately half of the patients who failed to achieve a clinical response after 10 weeks of ozanimod treatment benefited from an additional 5 to 10 weeks of ozanimod therapy

Introduction: The phase 3 True North (TN) study demonstrated the efficacy and safety of oral ozanimod (OZA) 0.92 mg once daily (equivalent to OZA HCl 1 mg) in patients (pts) with moderately to severely active ulcerative colitis (UC). The ongoing TN open-label extension (OLE) study is exploring longer-term efficacy and safety of OZA in UC. This interim analysis of the TN OLE evaluated the efficacy and safety of OZA in pts who received 98 weeks of continuous OZA treatment.
Method(s): Pts in clinical response (CRS) after 52weeks of continuous OZAduringTNwho rolled over into theOLE were included (data cutoff: September 30, 2020). Nearly 73% of pts had completed OLEWeek 46 (Week 98 of continuous OZA therapy) at the time of data cutoff when outcomes were measured. Endoscopy was performed annually throughout the OLE and was scored by Mayo endoscopic score. Efficacy data (Clinical Remission [CRM], CRS, Endoscopic Improvement [EI], and Corticosteroid-Free Remission [CFR]) were analyzed using observed cases (OC) and nonresponder imputation (NRI). Safety data were also recorded.
Result(s): Of 131 total pts in CRS at TNWeek 52, 83 (63%) were in CRM and 48 (37%) were in CRS only (but not CRM) on entry to the OLE. Demographic and clinical characteristics at TN baseline were similar for pts in both subgroups, except that a higher proportion of pts with only CRS at OLE entry were exposed to prior immunomodulators or tumor necrosis factor inhibitors at TN baseline. A high proportion of the overall population sustained CRM, CRS, EI, and CFR on OZA at OLE Week 46 in both OC and NRI analyses, with higher rates of CRM, EI, and CFR among pts entering the OLE in CRM (Table). Notably, 97% of all pts sustained CRS through overall Week 98 in OC analysis (64% in NRI analysis). Of the pts in CRS only at OLE entry, 55% achieved CRM by OLE Week 46 in OC analysis (NRI: 32%). Mean partialMayo score over time for the overall population is shown in the Figure. No new safety findings emerged from this extended analysis; 1 sudden death occurred during the OLE and was adjudicated to be unrelated to OZA.
Conclusion(s): This interim analysis of the TN OLE found that pts who achieved CRS or CRM after 1 year of OZA had a high rate of sustaining CRS, CRM, and EI for another year. Pts who after a year of OZA were in CRS could achieve CRM with continued OZA therapy. No additional safety signals were observed. (Figure Presented)

Introduction: The care of inflammatory bowel disease (IBD) has become increasingly complex and specialized. IBD education of gastroenterology (GI) trainees needs improvement and standardization. IBD 101, an annual course designed to introduce first-year GI fellows to various clinical topics in the management of IBD, was held on September 14, 2019. In this inaugural program, a select group of fellows (N=55 from 32 different programs) participated in a one-day course involving small group didactic sessions and Group Observed Structured Clinical Examinations (OSCEs) led by expert faculty members in seven clinical topics.
Method(s): To assess the long-term impact of IBD 101, email surveys were administered in May 2022 (the graduating year of the inaugural IBD 101 cohort) to all third-year GI fellows from participating programs, inclusive of both attendees and non-attendees. The primary outcome was comfort level discussing the 7 topics addressed at IBD 101, graded using a Likert scale (15 "strongly disagree" to '45 "strongly agree"). Information regarding each fellow's exposure to IBD education was collected.
Result(s): Thirty-six fellows completed surveys, of whom 21 (58%) were IBD 101 attendees and 15 (42%) were non-attendees. Overall, attendees reported equivalent or higher levels of comfort in each of the 7 topics than did non-attendees (Figure). In particular, a higher proportion of attendees strongly agreed with comfort in discussing pregnancy and IBD (43% vs. 13%; P=0.04) and loss of response to biologics (62% vs. 27%; P=0.13) than non-attendees. When assessing overall confidence, 76% of attendees reported comfort in all 7 categories, compared with 53% of non-attendees (P=0.15). Attending IBD 101 was associated with overall confidence (OR 5.21 [95% CI 0.91-29.9]; P=0.06) even after adjusting for presence of an IBD specialist at a fellow's home institution, number of IBD patients seen per month (<=5 vs. >5) and rotating through an IBD-only clinic or inpatient service (Table).
Conclusion(s): IBD 101, a primer for first-year GI trainees, was associated with increased comfort in the management of IBD, with more pronounced impact on challenging topics. IBD 101 is a valuable learning opportunity for first-year GI fellows with a durable benefit independent of individual access to IBD education, and we plan continued development, expansion and assessment of this program in collaboration with the ACG to further enhance the IBD education of the pipeline of GI trainees. (Figure Presented)

Introduction: Nearly a quarter of older adults with inflammatory bowel disease (IBD) require surgery. Patients with IBD are at risk for complications postoperatively and this risk is increased in older adults. However, little is known about the risk factors leading to these complications.We assessed risk factors associated with adverse postoperative outcomes among older adults who underwent IBD-related surgery, as well as evaluated trends in emergency vs. elective surgery in this population.
Method(s): Using the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database, we identified adults >=60 years of age who underwent an IBD-related intestinal resection from 2005-2019. Our primary outcome included a 30-day composite of mortality, readmission, reoperation, and/or what we identified as serious complications listed in NSQIP.
Result(s): In total, 9,640 intestinal resections were performed among older adults with IBD from 2005-2019, with 48.3% having undergone resection for Crohn's disease (CD), and 51.7% for ulcerative colitis (UC). Nearly 37% experienced an adverse outcome, with the most common complication being infection (20.21%). From 2005 to 2015, there was no decrease in the number of emergent cases among older adults. On univariate analysis, higher rates of adverse postoperative outcomes were seen with increasing age (p< 0.001), with nearly 50% of those >=80 years of age having an adverse outcome. Patients who underwent an emergency surgery had a higher likelihood of postoperative complications (66.86%; p< 0.001). On multivariable analysis, albumin <=3 (aOR 1.99; 95%CI 1.69-2.33), the presence of two or more comorbidities (aOR, 1.50; 95%CI 1.27-1.76), totally dependent functional status as compared to those partially dependent or independent (aOR, 7.28; 95%CI 3.14-21.2), and emergency surgery (aOR, 1.70; 95% CI 1.36-2.11) significantly increased the odds of an adverse outcome. (Figure)
Conclusion(s): Overall 37% of older adults with IBD experienced an adverse outcome as a result of IBD-related surgery. Limited functional health status, low preoperative serum albumin levels, and those undergoing emergent surgery were associated with a significantly higher risk. This is particularly important as the number of older adults with IBD is increasing, with a persisting number of emergency cases over time. Given the high rate of surgery in this population, future research should focus on preoperative rehabilitation, nutritional optimization, and timely surgery to improve outcomes. (Table Presented)

Introduction: As the inflammatory bowel disease (IBD) patient population ages, there will be an increasing number of individuals requiring advanced therapies. Although older age is thought to be associated with immunosenescence, there are data suggesting that older adults may be at higher risk for antibody development as the result of biologic use.
Method(s): Using a large commercial laboratory database (Prometheus Laboratories), we extracted infliximab (IFX) dosing as well as antibody to infliximab (ATI) levels for all individuals using this assay from 2015-2021. Our primary outcome was the presence of ATI (titer >3.1 U/mL). Frequencies were recorded as categorical variables with chi-square analysis used, and multivariable logistic regression was employed to assess the impact of IFX dose, age (< 60 years-old v. >=60 years-old), and IBD subtype on the development of ATI.
Result(s): Overall, there were 22,197 unique specimens, with 3,028 (13.6%) having ATI. When stratified by age, individuals >=60 years-old developed ATI 18.1% (473/2,612) of the time as compared to 15.0% (2,555/17,030) for individuals < 60 years of age (p< 0.01, Figure). Among all individuals with IFX dose < 10mg q8 weeks, older adults (>=60 years of age) were more likely to develop ATI as compared to younger adults (22.8% vs. 16.2%, respectively, p< 0.01); however, when IFX dose was >=10mg/kg q8 weeks, age >= 60 years-old was no longer significantly associated with the development of ATI (9.9% if < 60 years-old vs. 10.6% if >=60 years-old) on univariable analysis. Overall, older adults were less likely to receive IFX doses >=10mg/kg q8 weeks (38.4% in older adults vs. 49.7% in younger adults; p< 0.01). On multivariable analysis, age >=60 years-old (adjOR 1.35, 95%CI 1.20-1.51), IFX dose >= 10mg/kg q8 weeks (adjOR 0.53, 95%CI 0.49-0.57) and having ulcerative colitis as compared to Crohn's disease (adjOR 1.44, 95%CI 1.33-1.57) were independently associated with the development of ATI.
Conclusion(s): Older adults with IBD develop ATI more frequently than younger adults when adjusting for IFX dose and IBD subtype. However, when IFX dose >=10mg/kg q8 weeks, ATI was significantly less likely to develop among older adults, and occurred in a similar proportion of younger individuals. Further education is needed, highlighting that older adults with IBD are more likely to develop ATI as compared to younger adults, particularly when using lower doses of IFX, and that higher doses may decrease this likelihood. (Figure Presented)

BACKGROUND:Clinical and molecular subcategories of inflammatory bowel disease (IBD) are needed to discover mechanisms of disease and predictors of response and disease relapse. We aimed to develop a study of a prospective adult research cohort with IBD (SPARC IBD) including longitudinal clinical and patient-reported data and biosamples. METHODS:We established a cohort of adults with IBD from a geographically diverse sample of patients across the United States with standardized data and biosample collection methods and sample processing techniques. At enrollment and at time of lower endoscopy, patient-reported outcomes (PRO), clinical data, and endoscopy scoring indices are captured. Patient-reported outcomes are collected quarterly. The quality of clinical data entry after the first year of the study was assessed. RESULTS:Through January 2020, 3029 patients were enrolled in SPARC, of whom 66.1% have Crohn's disease (CD), 32.2% have ulcerative colitis (UC), and 1.7% have IBD-unclassified. Among patients enrolled, 990 underwent colonoscopy. Remission rates were 63.9% in the CD group and 80.6% in the UC group. In the quality study of the cohort, there was 96% agreement on year of diagnosis and 97% agreement on IBD subtype. There was 91% overall agreement describing UC extent as left-sided vs extensive or pancolitis. The overall agreement for CD behavior was 83%. CONCLUSION:The SPARC IBD is an ongoing large prospective cohort with longitudinal standardized collection of clinical data, biosamples, and PROs representing a unique resource aimed to drive discovery of clinical and molecular markers that will meet the needs of precision medicine in IBD.