Faculty Bibliography

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.

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.

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.

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:True North is a phase 3, randomized, double-blind, placebo-controlled trial conducted at 285 sites in 30 countries (NCT02435992). Treatment with once-daily ozanimod (an oral sphingosine 1-phosphate [S1P] receptor modulator selectively targeting S1P1 and S1P5) in patients with moderately-to-severely active ulcerative colitis (UC) showed significant improvements in primary and all key secondary endpoints. Here we report findings on the consistency of clinical and endoscopic endpoints in the global and North American population. METHODS:In True North, patients received either double-blind treatment with ozanimod 0.92 mg (equivalent to ozanimod HCl 1 mg) or matching placebo, or open-label ozanimod 0.92 mg over a 10-week induction period. Patients with clinical response to ozanimod at Week 10 were re-randomized 1:1 to receive double-blind maintenance treatment with ozanimod 0.92 mg or placebo through Week 52. The primary endpoint was proportion of patients in clinical remission at Weeks 10 and 52; key secondary endpoints included clinical response and endoscopic improvement. The global population included 1012 patients who received at least 1 dose of study medication during induction, and 457 who received at least 1 dose of study medication during maintenance. Here, we examine the results from the patients in the North American sites. RESULTS:A total of 247 patients were enrolled in North America, of which 167 received double-blind ozanimod (n=107) or placebo (n=60) during induction. At baseline, 41.1% and 48.3% of patients in the ozanimod and placebo groups, respectively, had previously received a biologic treatment for UC. At Week 10, 15.9% and 3.3% of patients in the ozanimod and placebo groups, respectively, achieved clinical remission. In addition, 46.7% and 15.0% achieved clinical response and 26.2% and 10.0% achieved endoscopic improvement in the ozanimod and placebo groups, respectively. In patients with prior exposure to tumor necrosis factor inhibitor (TNFi), the proportion with clinical response favored ozanimod (35.7%) vs placebo (11.5%), while the proportion with clinical remission and endoscopic improvement did not favor ozanimod. In patients with no prior TNFi exposure, greater responses were seen with ozanimod vs placebo for all 3 endpoints. During maintenance, 105 patients from North America were re-randomized to treatment with ozanimod (n=56) or placebo (n=49). At Week 52, 39.3% and 12.2% of patients in the ozanimod and placebo groups, respectively, achieved clinical remission. In addition, 58.9% and 26.5% achieved clinical response and 50.0% and 16.3% achieved endoscopic improvement in the ozanimod and placebo groups, respectively. The proportion of patients with clinical remission, clinical response, and endoscopic improvement favored ozanimod vs placebo regardless of prior TNFi use. These outcomes from the North American population are generally consistent with those previously reported from the global population. CONCLUSION/CONCLUSIONS:In this post-hoc analysis, consistent with the global population, ozanimod treatment for up to 52 weeks in North American patients with moderately-to-severely active UC showed benefits on clinical and endoscopic endpoints.

Introduction: Inflammatory bowel disease (IBD), psoriasis (PsO), and psoriatic arthritis (PsA) are immune-mediated inflammatory diseases characterized by dysregulation of the immune system. Evidence suggests that they share a common genetic and pathophysiologic pathway and that the presence of one increases the risk of developing others. While rates of PsO and PsA are increased in patients with IBD, data is lacking regarding whether phenotypic differences exist in patients with concurrent disease. In this study, we describe the disease characteristics of patients with IBD and PsO/PsA overlap.
Method(s): We performed a single-center case-control observational study. Eighty-five patients with IBD and PsO and/or PsA were identified and matched with a control group of patients with IBD alone in a 1:2 fashion based on age, sex and IBD type (n=190). Patient demographics, IBD phenotype and history, treatment patterns, and family history were collected.
Result(s): We identified 85 patients with IBD and PsO +/-PsA, matched with 190 controls. IBD 1 PsO/PsA patients were less frequently White (85% vs. 94%) and more frequently Asian (7% vs. 3%), compared with IBD only patients (P, 0.01, Table 1). There were no differences in extent of ulcerative colitis (UC) or distribution of Crohn's disease (CD), but patients with IBD alone were more likely to have penetrating Crohn's disease (48% vs. 7%; P, 0.01), prior hospitalizations (48% vs. 28%; P, 0.01), and prior surgeries (35% vs. 17%; P=0.02), compared to patients with overlap PsO +/-PsA. Rates of exposure to various biologic therapies were similar between the two groups, with the exception of decreased vedolizumab use in the IBD 1 PsO/PsA group (12% vs. 31% respectively; P, 0.01, Table 2). IBD only patients were more likely to have first-degree relatives (FDR) with IBD (35% vs. 23%; P=0.02) and numerically less likely to have a FDR with PsO or PsA (14% vs. 20%; P=0.21) than patients with PsO/PsA overlap (Table 1).
Conclusion(s): In this study, we report for the first time disease characteristics of patients with IBD and overlap PsO or PsA. Our results suggests that patients with IBD and PsO/PsA may have a less severe disease phenotype than patients with IBD alone, and that genetic risks may differ between these two groups. Further prospective studies are needed to confirm these findings

Introduction: Tofacitinib is a Janus kinase inhibitor approved for moderate to severe ulcerative colitis (UC). TOUR is the first real-world registry with prospectively collected data of tofacitinib efficacy in treating UC clinical symptoms in the first 8 week induction period.
Method(s): A total of 96 patients initiated tofacitinib at 15 academic and community GI practices. Clinical information and Mayo endoscopic scores were obtained. Patient reported outcome (PRO) data were collected using a daily electronic system for the first 14 days and at weeks 4 and 8. NIH PROMIS measures of social satisfaction, anxiety and depression were collected. Disease activity was measured using the simple clinical colitis activity index (SCCAI). A score of <=2 met criteria for remission; a score of<4 with a decrease by>1.5 points met criteria for response. Specific adverse events were collected. Paired t tests and P for trend compared changes in SCCAI at day 3, 7, 14, week 4 and week 8 to baseline. Outcomes were stratified by number of prior anti-tumor necrosis factor (anti-TNF) agents and Mayo endoscopic score at baseline. Bivariate analyses were performed using chi-squared test statistic.
Result(s): Of the 96 initiating tofacitinib, 95% had failed >= 1 anti-TNF and 67% had failed>= 2 biologics, 61.5% were on steroids and 81.3% had active disease. A total of 96% and 84% of patients remained on tofacitinib through week 4 and 8, respectively. The mean SCCAI of patients at baseline was 5.6, day 3 (4.6), day 7 (3.8), day 14 (3.3), week 4 (3.4), week 8 (3.2), P<0.001 for each, P for trend <0.001. Among those active at baseline, response was achieved in 49.3%, 50.8% and 47.4% of patients at week 2, 4 and 8; remission was achieved in 37.3%, 43.1% and 38.6% respectively. At week 8, there were no significant differences in response or remission in patients with ,2 vs >= 2 previous biologic therapies (P = 0.81) or severe inflammation on endoscopy (Mayo 3 vs Mayo 2 or 1) (P = 0.14). Improvements in all PROMIS measures were seen through week 8. A total of 3.1% of patients developed shingles, 10.4% had an infection requiring antibiotics. Fifteen patients (16%) discontinued tofacitinib in the first 8 weeks. Of these 15 patients, 33% (n 5 5) underwent colectomy.
Conclusion(s): In this prospective real-world study of the effectiveness and safety of tofacitinib in a refractory UC population, tofacitinib is associated with rapid response of various PROs within 1 week. No new safety signals were recognized

Introduction: Tofacitinib is an oral, small molecule JAK inhibitor for the treatment of UC. The OCTAVE clinical program included Phase 3 induction (OCTAVE Induction 1&2, NCT01465763 and NCT01458951) and maintenance (OCTAVE Sustain, NCT01458574) studies, and an open-label, long-term extension study (OCTAVE Open, NCT01470612).1,2 Stool frequency (SF) and rectal bleeding (RB) are important patient (pt)-reported outcomes (PROs) in measuring UC disease activity and treatment effect.
Method(s): This post hoc analysis reports long-term PRO measurements of RB and SF in pts from the OCTAVE clinical program. Analyses included pts from OCTAVE Induction 1&2, OCTAVE Sustain (responders from OCTAVE Induction 1&2), and OCTAVE Open (subpopulation in remission at Week [Wk]52 of OCTAVE Sustain, regardless of treatment). OCTAVE Open data from the final analyses (Aug 2020) are shown to Month (M)48. Endpoints included Mayo RB subscore (RBS)50, Mayo SF subscore (SFS)50 and <= 1, and partial Mayo score (PMS) remission (PMS <= 2 with no individual subscore> 1); analysis was descriptive (observed case).
Result(s): After induction therapy, 62.8-64.0% of tofacitinib 10 mg BID-treated pts achieved RBS50 vs 37.0-42.9% of placebo (PBO)-treated pts, and 55.4-60.9% of tofacitinib 10 mg BID-treated pts achieved SFS <= 1 (21.7-23.6% achieved SFS50) vs 33.6-33.7% of PBO-treated pts (11.2-12.6% for SFS50). Among OCTAVE induction responders re-randomized to maintenance therapy, 85.2%, 92.0%, and 94.5% of pts had RBS50, 79.6%, 89.3%, and 88.2% had SFS <= 1, and 40.7%, 56.3%, and 51.2% had SFS50 at Wk52 of OCTAVE Sustain for PBO, tofacitinib 5 mg BID, and tofacitinib 10 mg BID, respectively. Among pts who entered OCTAVE Open in remission and who were assigned to tofacitinib 5 mg BID, 93.5%, 95.7%, and 66.3% of pts maintained or achieved RBS50, SFS <= 1, and SFS50, respectively, at M48 of OCTAVE Open. Additionally, 94.6% of these pts maintained PMS remission (which includes RBS and SFS) at M48.
Conclusion(s): Most pts with UC demonstrated improvements in RBS and SFS after tofacitinib induction therapy. Among induction responders, the majority of pts maintained normalization or improvement in RB and/or SF in OCTAVE Sustain and up to M48 of OCTAVE Open. These data show robust and sustained improvement in key UC PROs with tofacitinib