Citations

INTRODUCTION: Advanced therapies infrequently achieve complete fistula closure in patients with Crohn's disease (CD). The primary objective of the STOMP2 clinical trial was to determine whether the implantable autologous cell therapy AVB-114 is effective in inducing remission of persistent Crohn's perianal fistulas versus standard of care. METHODS: Eligible patients had a single perianal fistula tract and had failed previous treatment or had documented medication intolerance to biologic or conventional CD therapy. All enrolled subjects underwent surgical fistula optimization and adipose tissue biopsy collection (to manufacture AVB-114) followed by 1:1 randomization to either standard of care (repeat fistula optimization including seton replacement) or AVB-114 implantation. The primary end point was combined fistula remission at 36 weeks, defined as closure of the external opening, no drainage of fluid despite gentle finger compression, and no collections >2 cm in at least 2 of the 3 dimensions on MRI. RESULTS: Subjects at 14 US sites were equally randomized to SoC (N = 24) or AVB-114 (N = 24). Week 36 combined remission was 8.3% and 45.8% for subjects randomized to SoC and AVB-114, respectively (38% difference, 95% CI 11%–60%; P = 0.0078). At week 36, MRI revealed no subjects with collections >2 cm, radiological improvement (≥50% decrease in the Magnetic Resonance Novel Index for Fistula Imaging in Crohn's Disease (MAGNIFI-CD) score from baseline) in 1 SoC subject and 3 AVB-114 subjects, and radiological healing (complete resolution of T2-weighted hyperintensity in fistula tract) in 2 SoC subjects and 5 AVB-114 subjects. Through week 36, there were 40 and 56 treatment emergent adverse events for SoC and AVB-114, respectively. There were no serious treatment emergent adverse events in the AVB-114 group through week 36. DISCUSSION: A significantly higher proportion of patients treated with AVB-114 achieved combined remission vs SoC, and the treatment was well tolerated. These data support the safety and efficacy of AVB-114 in persistent Crohn's perianal fistulas.

Introduction Targeted immunomodulators (eg, advanced therapies) effectively achieve symptomatic remission in patients with inflammatory bowel disease (IBD). However, ~25%–50% of patients with IBD achieving symptomatic remission with an advanced therapy may have continued endoscopically/radiologically active bowel inflammation, and it is uncertain whether changing alternative advanced therapies in asymptomatic patients with IBD will reduce bowel inflammation and achieve durable deep remission. Methods and analysis The QUality Outcomes Treating IBD to Target (QUOTIENT) study is an open-label, multicentre, pragmatic, randomised, controlled trial that aims to compare the efficacy and safety of switching to an alternative advanced therapy targeting endoscopic/radiological remission (treat-to-target) versus continuing the initial, or index, advanced therapy, in asymptomatic patients with IBD with moderate-to-severe endoscopic/radiological bowel inflammation. Enrolment is planned for ~250 participants in Canada/USA, randomised 1:1 to switching to alternative advanced therapy or continuing index advanced therapy, and then followed 104 weeks within routine clinical practice. Patient-reported outcomes measure efficacy and quality of life/treatment burden/safety. Primary endpoint is the time from randomisation to treatment failure. Ethics and dissemination The study is conducted in compliance with the protocol, ICH Good Clinical Practice, applicable regulatory requirements and appropriate review boards/independent ethics committees (approval numbers: Pro00077486; Pro00061437; STUDY00002062; 22-004171; i22-01269; IRB22-0890; IRB_00154397; 2000032384; SHIRB#2022.095-2; STUDY00007146; MMC#2024-18; REB#125290; 17784; Pro00142214; 20240660-01H), with documented written informed consent. Findings will be disseminated through peer-reviewed journals, scientific presentations, and publicly available Patient-Centered Outcomes Research Institute (PCORI) websites, including lay summaries. The Crohn’s & Colitis Foundation Education, Support, and Advocacy Department, and our patient advocacy stakeholder, will develop educational and marketing resources to communicate findings to a broad audience (>250 000 patients/caregivers/healthcare professionals). Trial registration number NCT05230173 .

Abstract Background Inflammatory bowel disease (IBD) management has become increasingly complex, and education varies across fellowship programs. IBD 101 was designed to introduce first-year gastroenterology (GI) fellows to IBD care and training. Methods In 2019, a cohort of fellows participated in a 1-day course with small group learning and group observed structured clinical examinations. Pre- and postcourse surveys were administered to evaluate the course. To assess the long-term impact, surveys were emailed in May 2022 to all third-year fellows from previously participating programs. The primary outcome was comfort managing IBD scenarios and information regarding each fellow’s exposure to IBD education. Results Fifty-five fellows from 32 programs participated. A total of 49 (89%) of 55 completed pre- and postcourse surveys. All fellows agreed that the course content was appropriate. In the postcourse survey, all fellows reported increased comfort managing IBD patients. Ninety-six percent of attendees stated that they would strongly recommend this course. Thirty-six fellows completed surveys in 2022, 21 (58%) attendees and 15 (42%) nonattendees. Attendees reported equivalent or higher levels of comfort compared with nonattendees. Higher global competence was noted among attendees (odds ratio, 5.21; 95% confidence interval, 0.91-29.9; P = .06) after adjusting for presence of a local IBD specialist, number of IBD patients seen monthly (≤5 vs >5), and rotation through an IBD service. Conclusions IBD 101, an introductory course for first-year GI trainees, was associated with increased comfort managing IBD with a durable benefit independent of individual access to IBD education. Continuation of this program will further enhance the IBD education of future GI fellows.

Abstract Background Extraintestinal manifestations (EIMs) of inflammatory bowel diseases (IBDs) are a common and debilitating feature of disease, occurring in up to 40% of patients with IBD, yet predicting who may develop them is difficult. The goal of our study was to better characterize which patients may be at highest risk of developing not only 1 EIM, but also multiple EIMs, across both diseases. Methods A retrospective study of participants enrolled in the SPARC IBD (Study of Prospective Adult Research Cohort with IBD) registry was performed, and demographic and clinical data were analyzed. A total of 1211 patients with data available on EIMs were included, and differences among variables with vs without EIMs were assessed. Results A total of 329 participants with at least 1 EIM were identified, compared with 882 participants without any EIMs. Crohn’s disease patients and women were more likely to have 2 or more EIMs (P = .005 and P ≤ .001, respectively). Participants with ocular manifestations were likeliest to have at least 2 EIMs (P ≤ .001). Even when diagnosis was controlled for, involvement of the right colon (P = .021) was predictive of IBD-associated arthritis across both diseases in a multivariate generalized linear model. Conclusions This is the first comprehensive large-cohort assessment of how EIMs relate to one another at the individual vs systems levels. Further, our analysis is the first to recognize specific locations of colon involvement associated with EIMs of IBD, regardless of IBD type. These results are important in identifying patients at risk of developing future EIMs and may help with risk stratification when choosing treatments.

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.

INTRODUCTION: Limited guidance exists for the postdischarge care of patients with ulcerative colitis hospitalized for moderate-severe flares. METHODS: RAND methodology was used to establish appropriateness of inpatient and postdischarge steroid dosing, discharge criteria, follow-up, and postdischarge biologic or small molecule initiation. A literature review informed on the panel's voting, which occurred anonymously during 2 rounds before and after a moderated virtual session. RESULTS: Methylprednisolone 40–60 mg intravenous every 24 hours or hydrocortisone 100 mg intravenous 3 times daily is appropriate for inpatient management, with methylprednisolone 40 mg being appropriate if intolerant of higher doses. It is appropriate to discharge patients once rectal bleeding has resolved (Mayo subscore 0–1) and/or stool frequency has returned to baseline frequency and form (Mayo subscore 0–1). It is appropriate to discharge patients on 40 mg of prednisone after observing patients for 24 hours in hospital to ensure stability before discharge. For patients being discharged on steroids without in-hospital biologic or small molecule therapy initiation, it is appropriate to start antitumor necrosis factor (TNF) therapy after discharge for anti-TNF-naive patients. For anti-TNF-exposed patients, it is appropriate to start vedolizumab or ustekinumab for all patients and tofacitinib for those with a low risk of adverse events. It is appropriate to follow up patients clinically within 2 weeks and with lower endoscopy within 4–6 months after discharge. DISCUSSION: We provide recommendations on the inpatient and postdischarge management of patients with ulcerative colitis hospitalized for moderate-severe flares.

Abstract Background Tofacitinib is an oral, small molecule JAK inhibitor for the treatment of ulcerative colitis (UC). These post hoc analyses assessed associations between C-reactive protein (CRP), partial Mayo score (PMS), and efficacy outcomes during tofacitinib induction in UC. Methods Patients received tofacitinib 10 mg twice daily (BID) in an 8-week, phase 2 induction study and 2 identical, 8-week, phase 3 induction studies (OCTAVE Induction 1&2); induction nonresponders (IndNR) received an additional 8 weeks of tofacitinib 10 mg BID in an open-label, long-term extension study. Associations between CRP and PMS, and efficacy outcomes (clinical response, clinical remission, endoscopic improvement, and endoscopic remission) were analyzed using univariate and multivariable logistic regression and receiver operating characteristic curves. Results Changes from baseline in the logarithm of CRP ([log]CRP) and PMS at week 4 were associated with clinical response at week 8 (univariate: per unit, odds ratio [OR], 0.55 [95% confidence interval (CI), 0.48-0.62]; and 0.42 [0.37-0.47], respectively). Among IndNR, change from baseline in PMS at week 8 was associated with clinical response at week 16 (univariate: per unit, OR, 0.59; 95% CI, 0.46-0.75). C-reactive protein at week 4 (area under the curve [AUC] > 0.6) and PMS at weeks 2 and 4 (AUC, > 0.7) generally exhibited predictive value for week 8 efficacy outcomes. Conclusions Patients who achieved clinical response at week 8 had larger decreases in CRP and PMS at week 4 than patients who did not. IndNR who achieved clinical response at week 16 with extended tofacitinib induction had a larger decrease in PMS at week 8 vs those who did not. ClinicalTrials.gov:NCT00787202;NCT01465763;NCT01458951;NCT01470612.

Abstract 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.

SummaryBackgroundHyperbaric oxygen has been reported to improve disease activity in hospitalised ulcerative colitis (UC) patients.AimTo evaluate dosing strategies with hyperbaric oxygen for hospitalised UC patients.MethodsWe enrolled UC patients hospitalised for acute flares (Mayo score 6‐12). Initially, all patients received 3 days of hyperbaric oxygen at 2.4 atmospheres (90 minutes with two air breaks) in addition to intravenous steroids. Day 3 responders (reduction of partial Mayo score ≥ 2 points and rectal bleeding score ≥ 1 point) were randomised to receive a total of 5 days vs 3 days of hyperbaric oxygen.ResultsWe treated 20 patients with hyperbaric oxygen (75% prior biologic failure). Day 3 response was achieved in 55% (n = 11/20), with significant reductions in stool frequency, rectal bleeding and CRP (P < 0.01). A more significant reduction in disease activity was observed with 5 days vs 3 days of hyperbaric oxygen (P = 0.03). Infliximab or colectomy was required in only three patients (15%) despite a predicted probability of 80% for second‐line therapy. Day 3 hyperbaric oxygen responders were less likely to require re‐hospitalisation or colectomy by 3 months vs non‐responders (0% vs 66%, P = 0.002). No treatment‐related adverse events were observed.ConclusionHyperbaric oxygen appears to be effective for optimising response to intravenous steroids in UC patients hospitalised for acute flares, with low rates of re‐hospitalisation or colectomy at 3 months. An optimal clinical response is achieved with 5 days of hyperbaric oxygen. Larger phase 3 trials are needed to confirm efficacy and obtain labelled approval.

Abstract Background Vedolizumab effectiveness estimates immediately after Food and Drug Administration (FDA) approval for ulcerative colitis (UC) and Crohn’s disease (CD) are limited by use in refractory populations. We aimed to compare treatment patterns and outcomes of vedolizumab in 2 time frames after FDA approval. Methods We used 2 data sets for time trend analysis, an academic multicenter vedolizumab consortium (VICTORY) and the Truven MarketScan database, and 2 time periods, May 2014–June 2015 (Era 1) and July 2015–June 2017 (Era 2). VICTORY cumulative 12-month clinical remission, corticosteroid-free remission, and mucosal healing rates, and Truven 12-month hospitalization and surgery rates, were compared between Eras 1 and 2 using time-to-event analyses. Results A total of 3661 vedolizumab-treated patients were included (n = 1087 VICTORY, n = 2574 Truven). In both cohorts, CD and UC patients treated during Era 2 were more likely to be biologic naïve. Compared with Era 1, Era 2 CD patients in the VICTORY consortium had higher rates of clinical remission (31% vs 40%, P = 0.03) and mucosal healing (42% vs 58%, P < 0.01). These trends were not observed for UC. In the Truven database, UC patients treated during Era 2 had lower rates of inflammatory bowel disease–related hospitalization (22.4% vs 9.6%, P < 0.001) and surgery (17.2% vs 9.4%, P = 0.008), which was not observed for CD. Conclusion Since FDA approval, remission and mucosal healing rates have increased for vedolizumab-treated CD patients, and vedolizumab-treated UC patients have had fewer hospitalizations and surgeries. This is likely due to differences between patient populations treated immediately after drug approval and those treated later.