Faculty Bibliography

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/BACKGROUND:There is significant variation in processes and outcomes of care for patients with inflammatory bowel disease (IBD), suggesting opportunities to improve quality of care. We aimed to determine whether a structured quality of care program can improve IBD outcomes, including the need for unplanned health care utilization. METHODS:We used a structured approach to improve adult IBD care in 27 community-based gastroenterology practices and academic medical centers. Patient-reported outcomes (PRO) and health care utilization were collected at clinical visits. Outcomes were monitored monthly using statistical process control charts; improvement was defined by special cause (nonrandom) variation over time. Multivariable logistic regression was applied to patient-level data. Nineteen process changes were offered to improve unplanned health care utilization. Ten outcomes were assessed, including disease activity, remission status, urgent care need, recent emergency department use, hospitalizations, computed tomography scans, health confidence, corticosteroid or opioid use, and clinic phone calls. RESULTS:We collected data prospectively from 20,382 discrete IBD visits. During the 15-month project period, improvement was noted across multiple measures, including need for urgent care, hospitalization, steroid use, and opioid utilization. Adjusted multivariable modeling showed significant improvements over time across multiple outcomes including urgent care need, health confidence, emergency department utilization, hospitalization, corticosteroid use, and opioid use. Attendance at monthly coached webinars was associated with improvement. DISCUSSION/CONCLUSIONS:Outcomes of IBD care were improved using a structured quality improvement program that facilitates small process changes, sharing of best practices, and ongoing feedback. Spread of these interventions may facilitate broad improvement in IBD care when applied to a large population.

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.

BACKGROUND:With the management of inflammatory bowel disease (IBD) becoming increasingly complex, incorporating preventive care health maintenance measures can be challenging. The aim of developing these updated recommendations is to provide more specific details to facilitate their use into a busy clinical practice setting. METHOD:Fifteen statements were formulated with recommendations regarding the target, timing, and frequency of the health maintenance interventions in patients with IBD. We used a modified Delphi method and a literature review to establish a consensus among the panel of experts. The appropriateness of each health maintenance statement was rated on a scale of 1 to 5 (1-2 as inappropriate, and 4-5 as appropriate) by each panelist. Interventions were considered appropriate, and statements were accepted if ≥80% of the panelists agreed with a score ≥4. RESULTS:The panel approved 15 health maintenance recommendations for adults with IBD based on the current literature and expert opinion. These recommendations include explicit details regarding specific screening tools, timing of screening, and vaccinations for adults with IBD. CONCLUSIONS:Patients with IBD are at an increased risk for infections, malignancies, and other comorbidities. Given the complexity of caring for patients with IBD, this focused list of recommendations can be easily incorporated in to clinical care to help eliminate the gap in preventative care for patients with IBD.

BACKGROUND:Differentiating between enteric infection and relapse of inflammatory bowel disease (IBD) is a common clinical challenge. Few studies have evaluated the impact of multiplex gastrointestinal polymerase chain reaction (GI PCR) pathogen panels on clinical practice compared to stool culture. Our aim was to compare the impact of PCR stool testing to conventional stool testing in outpatients presenting with relapse of IBD. METHODS:In a retrospective cohort study of outpatients with IBD presenting to NYU Langone Health with flare from September 2015 to April 2019, we compared patients who underwent stool testing with GI PCR to age-, sex-, and IBD-subtype-matched patients who underwent culture and ova and parasite exam (conventional testing). The primary outcome was IBD therapy escalation after testing. Secondary outcomes included rates of posttesting endoscopy, abdominal radiography, antibiotics, and IBD-related emergency department visits, hospitalizations, and abdominal surgeries. RESULTS:We identified 134 patients who underwent GI PCR matched to 134 patients who underwent conventional testing. Pathogens were more frequently identified on GI PCR (26 vs 5%; P < 0.01). We found that GI PCR was associated with less escalation in IBD therapy (16 vs 29%; P < 0.01) and fewer posttest endoscopies (10% vs 18%; P = 0.04), with no differences in IBD outcomes. On multivariate analysis, testing with GI PCR was associated with an odds ratio of 0.26 (95% confidence interval, 0.08-0.84; P = 0.02) for escalation of IBD therapies. CONCLUSIONS:Testing with GI PCR was associated with higher rates of pathogen detection and lower rates of IBD therapy escalation and endoscopy in the outpatient setting. These changes in management were not associated with a difference in IBD outcomes.

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

Introduction: Previous studies have demonstrated that exposure to anti-TNFa medications or immunomodulators (IMM) does not increase the risk of new or recurrent cancer in patients with inflammatory bowel disease (IBD) and a previous history of cancer. There is little data regarding this risk after the use of newer biologics such as ustekinumab and vedolizumab. In this study, we assessed whether patients with IBD and a history of previous cancer who are exposed to these newer agents have an increased risk of developing subsequent cancer.
Method(s): We performed a retrospective cohort study of patients with IBD and cancer from a single academic medical center between January 2013 and December 2020. We recorded information on demographics, cancer type and treatment, and IBD characteristics and drug exposures. The primary exposure was type of IBD monotherapy after a cancer diagnosis. The primary outcome was development of new or recurrent cancer.
Result(s): Of 401 patients with IBD and a history of cancer, 37 subsequently received vedolizumab, 14 ustekinumab, 31 IMM, 41 anti-TNF, 11 combination anti-TNF with an IMM, and 267 were not exposed to any immunosuppression following a cancer diagnosis (Table 1). There were no differences in duration of IBD, median age at cancer diagnosis, or smoking history. During a total median follow-up of 52 months, 81 (20%) patients developed incident cancer including 6 (16%) exposed to vedolizumab, 2 (14%) to ustekinumab, 3 (10%) to IMM, 12 (29%) to anti-TNF, 2 (18%) to combination anti-TNF with an IMM, and 56 (21%) with no immunosuppression (P = 0.41). Sensitivity analyses assessing any history of exposure to vedolizumab or ustekinumab, inclusive of both single and multiple biologic exposures, also did not reveal an increased rate of incident cancer.
Conclusion(s): In this single-center study, vedolizumab or ustekinumab monotherapy in patients with IBD and a history of cancer was not associated with an increase in new or recurrent cancer compared with anti-TNF, IMM, or no immunosuppression. Prospective studies are needed to confirm this conclusion

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

Background: Optimal ustekinumab levels (UST) in Crohn disease (CD) treatment have not been defined. We set out to define the optimal UST to differentiate between remission and active CD, as defined using the serum-based endoscopic healing index (EHI). Methods: Paired serum UST and EHI tests were analyzed. Remission was defined as EHI <20. Active disease was defined as EHI ≥50. The proportion of patients in remission was compared across UST quartiles. UST in subjects with EHI <20 and EHI ≥50 were compared. An area under receiver operating characteristic curve was generated to identify an optimal UST to differentiate between active disease and remission. Results: A total of 337 unique patients were identified; median UST and EHI were 5.0 μg/mL [interquartile range (IQR) 2.7-9.1] and 37 (IQR 26-53), respectively. EHI <20 (remission) was found in 57 (16.9%) patients. EHI ≥50 (active disease) was found in 97 (28.8%) patients. Higher proportions of subjects were in remission for increasing UST quartiles, P = 0.01. Median UST in patients with EHI <20 and EHI ≥50 were 7.5 μg/mL (IQR 4.6-10.9) and 3.1 μg/mL (IQR 1.8-6.6), respectively, P < 0.001. An UST threshold of 3.75 μg/mL optimally differentiated between active disease and remission (area under the curve 0.725). UST levels >3.75 μg/mL were associated with a lower proportion of subjects with active disease (EHI ≥50; 18.9%) compared with UST levels ≤3.75 μg/mL (45.6%, P < 0.001). Conclusions: Using the EHI, we identified a threshold UST level of 3.75 μg/mL to optimally differentiate between active and quiescent CD. These data suggest that UST serum concentrations of >3.75 μg/mL are optimally associated with endoscopic remission in CD.