Regueiro, Miguel

SummaryBackgroundThere is limited real‐world data on comparative effectiveness of different biologic or small molecule agents as second‐line therapies in patients with ulcerative colitis (UC) with prior exposure to a tumour necrosis factor inhibitor (TNFi).MethodsWe conducted a retrospective cohort study using TriNetX, a multi‐institutional database to assess the efficacy of tofacitinib, vedolizumab and ustekinumab in patients with ulcerative colitis (UC) with prior exposure to a TNFi. Failure of medical therapy was defined as a composite outcome of intravenous steroids or colectomy within 2 years. One‐to‐one propensity score matching was performed for demographics, disease extent, mean haemoglobin, C‐reactive protein, albumin and calprotectin, prior IBD medications and steroid use between cohorts.ResultsAmong 2141 patients with UC and prior exposure to TNFi, 348 (16.2%), 716 (33.4%) and 1077 (50.3%) were switched to tofacitinib, ustekinumab and vedolizumab, respectively. After propensity‐score matching, there was no difference in the composite outcome (aOR: 0.77, 95% CI: 0.55–1.07) but higher risk of colectomy (aOR: 2.69, 95% CI: 1.31–5.50) in the tofacitinib cohort than the vedolizumab cohort. There was no difference in the risk of composite outcome (aOR: 1.29, 95% CI: 0.89–1.86) but higher risk of colectomy (aOR: 2.63, 95% CI: 1.24–5.58) in the tofacitinib cohort than the ustekinumab cohort. The vedolizumab cohort had a higher risk of composite outcome (aOR: 1.67, 95% CI: 1.29–2.16) than the ustekinumab cohort.ConclusionUstekinumab might be the preferred second‐line therapy over tofacitinib and vedolizumab in patients with UC that were previously exposed to a TNFi.

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.

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.

AbstractIleocolic resection (ICR) is the most common surgical procedure in Crohn disease (CD). There are many surgical techniques for performing ICRs and subsequent anastomoses. Recurrence of CD after ICR is common, often clinically silent, and thus requires monitoring including periodic use of endoscopy to detect early active disease. There is emerging evidence that surgical approaches may influence CD recurrence. This review explores the various surgical considerations, the data behind each decision, and how these techniques influence subsequent endoscopic surveillance.

Abstract Background and Aims To correlate histologic activity in surveillance colonoscopies with the development of colorectal neoplasia in ulcerative colitis [UC]. Methods Colorectal biopsies during surveillance [N = 764] from 52 UC patients with colorectal neoplasia were compared to 122 patients without neoplasia enrolled in a prospective natural history registry. All biopsies were scored using validated histologic scoring systems (Geboes score, Nancy histopathologic index [NHI], and Robarts histopathologic index [RHI]). Clinical, endoscopic, and histologic data were correlated with the development of colorectal neoplasia. Results In multivariable analysis, mean RHI (hazard ratio [HR] 1.07 for each 1-unit increase in RHI, 95% confidence interval [CI] 1.03–1.12, p = 0.002) and mean NHI [HR 1.89 for each 1-unit increase in NHI, 95% CI 1.34–2.67, p = 0.002] for the entire surveillance period were significantly associated with colorectal neoplasia development. Shorter surveillance interval and increasing age were associated with increased risk of neoplasia development whereas mean Mayo endoscopic score was not significant. To generate a clinically useful measure of neoplasia risk, mean histologic activity in the preceding 5 years before the study endpoint was correlated with neoplasia development. In the preceding 5 years of surveillance, a mean RHI ≥ 8 had a 7.53-fold increased risk [95% CI 2.56–12.16, p < 0.001] and mean NHI ≥ 1.9 had a 5.89-fold increased risk [95% CI 2.18–15.92, p < 0.001] of developing colorectal neoplasia. Conclusions Persistent histologic activity during multiple surveillance episodes is an independent predictor of colorectal neoplasia. Mean RHI and mean NHI during a 5-year colonoscopic surveillance period can be used to assess risk for colorectal neoplasia and optimize UC surveillance.

Abstract Background The level of inflammatory bowel disease (IBD) training in general gastroenterology fellowship is often insufficient to prepare trainees to deliver advanced IBD care in practice. Advanced IBD fellowships have been developed to fill this training gap, but there is no established curriculum, and significant variability exists across programs. Entrustable professional activities (EPAs) are practical and realistic objectives that define essential tasks of a specialty that physicians should master to be competent during independent practice. The American College of Gastroenterology (ACG) and Crohn’s & Colitis Foundation (Foundation) established a task force to develop and appraise EPAs for advanced IBD fellowship. Methods Entrustable professional activities were developed using a multistep approach in a similar manner to other specialties. Initial EPAs identified via focus groups were evaluated, critiqued, and changed using an iterative model of feedback. The final EPAs were selected after the task force conducted a 3-phase modified Delphi method consisting of 2 sequential rounds of web-based voting and an in-person consensus meeting. Results Ten EPAs for advanced IBD fellowship were established including detailed descriptions with the associated knowledge, skills, and attitudes for each that can serve as curricular milestones. Conclusion Ten EPAs describing the core work of an advanced IBD fellowship–trained physician have been established by a multisociety task force. Creating EPAs for an advanced curriculum comes with unique challenges, particularly the need to prevent duplication of prior training competencies while demonstrating the potential for unique milestones.