Faculty Bibliography

BACKGROUND/UNASSIGNED:In ulcerative colitis (UC), endoscopic improvement, defined as a Mayo Endoscopic Score (MES) of 0 or 1, is a target of treatment. The aim of our study was to evaluate the risk of clinical relapse between patients with an MES of 0 or 1 and determine if histologic activity using the Robarts Histopathologic Index (RHI) was predictive of clinical relapse. METHODS/UNASSIGNED:UC patients with an MES score of 0 or 1, no prior colectomy, and at least 1 year of outpatient follow-up after colonoscopy were included. Demographic, clinical characteristics, and clinical relapse were retrospectively collected. Biopsy specimens were read by a gastrointestinal pathologist. Primary outcome was defined as a composite of relapse requiring change in medical therapy, new steroid use, UC-related hospitalization, and/or colectomy. RESULTS/UNASSIGNED: = .008). CONCLUSIONS/UNASSIGNED:UC patients with endoscopic improvement have a high rate of clinical relapse over time. Histologic activity is a predictor of clinical relapse.

In individuals with inflammatory bowel disease (IBD), extraintestinal manifestations (EIMs) represent a significant burden of illness, with reported prevalence rates of up to 50%.¹ Of the various types of EIMs, the most commonly involved organ system is the musculoskeletal system.

BACKGROUND:Postoperative recurrence (POR) of Crohn's disease (CD) is common after surgical resection. We aimed to compare biologic type and timing for preventing POR in adult CD patients after ileocecal resection (ICR). METHODS:We performed a retrospective cohort study of CD patients who underwent an ICR at 2 medical centers. Recurrence was defined by endoscopy (≥ i2b Rutgeerts score) or radiography (active inflammation in neoterminal ileum) and stratified by type and timing of postoperative prophylactic biologic within 12 weeks following an ICR (none, tumor necrosis factor antagonists [anti-TNF], vedolizumab, and ustekinumab). RESULTS:We identified 1037 patients with CD who underwent an ICR. Of 278 (26%) who received postoperative prophylaxis, 80% were placed on an anti-TNF agent (n = 223) followed by ustekinumab (n = 28, 10%) and vedolizumab (n = 27, 10%). Prophylaxis was initiated in 35% within 4 weeks following an ICR and in 65% within 4 to 12 weeks. After adjusting for factors associated with POR, compared with no biologic prophylaxis, the initiation of an anti-TNF agent within 4 weeks following an ICR was associated with a reduction in POR (adjusted hazard ratio, 0.61; 95% CI, 0.40-0.93). Prophylaxis after 4 weeks following an ICR or with vedolizumab or ustekinumab was not associated with a reduction in POR compared with those who did not receive prophylaxis. CONCLUSION/CONCLUSIONS:Early initiation of an anti-TNF agent within 4 weeks following an ICR was associated with a reduction in POR. Vedolizumab or ustekinumab, at any time following surgery, was not associated with a reduction in POR, although sample size was limited.

BACKGROUND:Tofacitinib is an oral, small-molecule JAK inhibitor for the treatment of ulcerative colitis (UC). Using a novel electronic reporting tool, we aimed to prospectively describe the onset of tofacitinib efficacy during induction therapy in a real-world study. METHODS:Patient-reported outcome data (PROs) including the simple clinical colitis activity index (SCCAI), PRO Measurement Identification Systems (PROMIS) measures, and adverse events were collected daily for the first 14 days and at day 28 and 56. Paired t tests and P for trend were utilized to compare changes in SCCAI over time. Bivariate analyses and logistic regression models were performed to describe response (SCCAI <5) and remission (SCCAI ≤2) by clinical factors. RESULTS:Of all included patients (n = 96), 67% had failed ≥2 biologics, and 61.5% were on concomitant steroids. Starting at day 3, PROs showed significant and persistent decline of the mean SCCAI (-1.1, P < 000.1) including significantly lower SCCAI subscores for stool frequency (-0.3; P < .003), bleeding (-0.3; P < .0002) and urgency (-0.2; P < .001). Steroid-free remission at day 14, 28, and 56 was achieved in 25%, 30.2%, and 29.2% of patients, respectively. Neither prior biologics nor endoscopic severity were independently predictive of response or remission in multivariate models. Numeric improvements in all PROMIS measures (anxiety, depression, social satisfaction) were seen through day 56. Rates of discontinuation due to adverse events were low. CONCLUSIONS:In this prospective real-world study, tofacitinib resulted in a rapid and persistent improvement in UC disease activity PROs. The safety findings were consistent with the established safety profile of tofacitinib.

BACKGROUND:Tofacitinib is an oral small molecule Janus kinase inhibitor for the treatment of ulcerative colitis (UC). The tofacitinib OCTAVE clinical program included phase III induction (OCTAVE Induction 1 and 2) and maintenance (OCTAVE Sustain) studies, and an open-label, long-term extension study (OCTAVE Open). OBJECTIVE:This post hoc analysis assessed selected long-term, disease-specific patient-reported outcome (PRO) and health-related quality-of-life (HRQoL) measurements in patients with UC receiving tofacitinib in the OCTAVE clinical program. METHODS:Analyses included patients from OCTAVE Open assigned to tofacitinib 5 mg twice daily (subpopulation in remission at Week 52 of OCTAVE Sustain). OCTAVE Open data from the final analyses are shown to Month 48. Endpoints included rectal bleeding subscore (RBS) = 0, stool frequency subscore (SFS) ≤ 1, and HRQoL measure, Inflammatory Bowel Disease Questionnaire (IBDQ) remission (IBDQ total score ≥ 170); with non-responder imputation for missing data at all visits, and last observation carried forward for visits after a patient advanced to the next study (NRI-LOCF). Observed cases were also assessed. RESULTS:At Month 48, of 175 patients, 95 (54.3%) and 96 (54.9%) achieved/maintained RBS = 0 and SFS ≤ 1, respectively (NRI-LOCF). Additionally, 93 (53.1%) patients achieved/maintained IBDQ remission at Month 48 (NRI-LOCF). CONCLUSIONS:Among patients who entered OCTAVE Open in remission, most maintained normalization of rectal bleeding and improvement in stool frequency for ≤ 4 years of follow-up in OCTAVE Open. IBDQ remission was also generally maintained in OCTAVE Open. These data show robust maintenance of key UC PROs and durability of response with tofacitinib 5 mg twice daily. TRIAL REGISTRATION/BACKGROUND:http://www. CLINICALTRIALS/RESULTS:gov (NCT01465763 [21/10/2011]; NCT01458951 [21/10/2011]; NCT01458574 [21/10/2011]; NCT01470612 [21/10/2011]).

OBJECTIVE:We evaluated the real-world effectiveness and safety of ustekinumab (UST) in patients with Crohn's disease (CD). METHODS:This study utilized 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 remission were assessed using time-to-event and clinical predictors were assessed by multivariate Cox proportional hazard analyses. Serious infections and adverse events were defined as those requiring hospitalization or treatment discontinuation. RESULTS:A total of 1113 patients (51.8% female, 90% prior anti-TNF exposure) were included, with a median follow-up of 386 days. Cumulative rates of clinical, steroid-free, endoscopic, and radiographic remission at 12 months were 40%, 32%, 39%, and 30%, respectively. Biologic-naïve patients achieved significantly higher rates of clinical and endoscopic remission at 63% and 55%, respectively. On multivariable analyses, prior anti-TNF (HR, 0.72; 95% CI, 0.49-0.99) and vedolizumab exposure (HR, 0.65; 95% CI, 0.48-0.88) were independently associated with lower likelihoods of achieving endoscopic remission. In patients who experienced loss of remission, 77/102 (75%) underwent dose optimization, and 44/77 (57%) achieved clinical response. An additional 152/681 (22.3%) patients were dose optimized as a result of primary non- or incomplete response to UST, of whom 40.1% (61/152) responded. Serious infections occurred in 3.4% of patients, while other non-infectious 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. CONCLUSIONS: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 bio-naive patients, and dose escalation may recapture clinical response.

BACKGROUND/UNASSIGNED:The COVID-19 pandemic led to the urgent implementation of telehealth visits in inflammatory bowel disease (IBD) care; however, data assessing feasibility remain limited. OBJECTIVES/UNASSIGNED:We looked to determine the completion rate of telehealth appointments for adults with IBD, as well as to evaluate demographic, clinical, and social predictors of incomplete appointments. DESIGN/UNASSIGNED:We conducted a retrospective analysis of all patients with IBD who had at least one scheduled telehealth visit at the NYU IBD Center between 1 March 2020 and 31 August 2021, with only the first scheduled telehealth appointment considered. METHODS/UNASSIGNED:Medical records were parsed for relevant covariables, and multivariable logistic regression was used to estimate the adjusted association between demographic factors and an incomplete telehealth appointment. RESULTS/UNASSIGNED: = 0.22). After adjustment, patients with CD had higher odds of an incomplete appointment as compared to patients with UC [adjusted odds ratio (adjOR): 1.37, 95% confidence interval (CI): 1.10-1.69], as did females (adjOR: 1.26, 95% CI: 1.04-1.54), and patients who had a non-first-degree relative listed as an emergency contact (adjOR: 1.69, 95% CI: 1.16-2.44). While age ⩾60 years was not associated with appointment completion status, we did find that age >80 years was an independent predictor of missed telehealth appointments (adjOR: 2.92, 95% CI: 1.12-7.63) when compared to individuals aged 60-70 years. CONCLUSION/UNASSIGNED:telehealth, particularly those aged 60-80 years, may therefore provide an additional venue to complement in-person care.

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