Citations

Abstract Background Upper gastrointestinal Crohn’s disease (UGICD) is an uncommon phenotype with limited management guidelines. We reviewed evidence on the safety and efficacy of pharmacological interventions for UGICD. Methods We searched MEDLINE, Embase, and Cochrane CENTRAL (1990-2025) for randomized controlled trials (RCTs) and comparative observational studies evaluating pharmacological or dietary interventions for UGICD, including esophagus to jejunum. Two reviewers screened studies, extracted data, and assessed bias (Newcastle–Ottawa Scale). Primary outcomes were clinical remission and response. Due to limited, heterogeneous evidence, data are summarized descriptively. Results Of 1207 citations, 11 observational studies (nine retrospective, two prospective) and post-hoc analyses from two RCTs met the criteria, involving 387 patients. Most had ileocolonic involvement (280/387; 72.3%); only 8.5% (33/387) had isolated UGICD. Five studies (137 patients) reported esophageal CD. Follow-up ranged from 6 weeks to 28 years. Interventions and outcomes varied. Anti-tumor necrosis factor (anti-TNF) drugs and corticosteroids, alone or combined with other treatments, were associated with improvements in clinical outcomes, endoscopic healing, and histology, but controlled data are lacking. Other therapies, including proton pump inhibitors, H2-receptor antagonists, enteric nutrition, immunomodulators, anti-integrins, and anti-interleukin12/23, showed moderate to minimal improvement. Conclusions Our systematic review highlights a paucity of evidence to inform therapeutic strategies in UGICD. Positive outcomes were reported for corticosteroids and anti-TNF, but from small observational and uncontrolled studies. Data for most advanced therapies remain limited, highlighting a large unmet need to inform clinical practice.

INTRODUCTION: We conducted a retrospective cohort study comparing the safety of advanced therapies in patients with ulcerative colitis (UC). METHODS: Using an administrative claims database (OptumLabs Data Warehouse), we identified patients with UC who initiated treatment with tumor necrosis factor-α (TNF) antagonists, anti-integrin agents, anti-interleukin, Janus kinase inhibitors (JAK), or sphingosine-1 phosphate receptor modulators between 2016 and 2022 and had followed up for at least 1 year before and after treatment initiation. We compared the risk of serious infections, venous thromboembolism, and major adverse cardiovascular events through multinomial propensity score-based inverse probability weighting, with propensity scores estimated through generalized boosted models that accounted for disease characteristics, healthcare utilization, comorbidities, and previous and concomitant medications, and the competing risk of mortality. We calculated cause-specific hazard ratios (HR) and 95% confidence intervals for multiple treatment comparisons. RESULTS: We included 9,430 patients with UC treated with TNF antagonists (n = 4,111), anti-integrins (n = 3,165), anti-ILs (n = 1,342), JAK inhibitors (n = 701), or sphingosine-1 phosphate receptor modulators (n = 111), followed over median 27 months. After adjusting for confounding variables, anti-ILs were associated with a lower risk of serious infections compared with TNF antagonists (HR, 0.66 [95% confidence interval, 0.51–0.87]) and anti-integrins (HR, 0.75 [0.57–0.98]). JAK inhibitors were associated with a lower risk of serious infections compared with TNF antagonists (HR, 0.66 [0.46–0.94]). The incidence of venous thromboembolism (incidence rate, 1.4–2.0 per 100 py) and major adverse cardiovascular event (0.5–1.0 per 100 py) was very low, without any significant differences across agents. DISCUSSION: In a real-world cohort of patients with UC, anti-ILs and JAK inhibitors were associated with a lower risk of serious infections and may offer net benefit, especially in patients with previous TNF antagonist exposure.

Abstract Background and Aims Seven new advanced therapies, belonging to three new classes, have been approved for the treatment of inflammatory bowel diseases (IBD) since 2021. We examined trends in utilization of advanced therapies in the USA since 2021. Methods Using de-identified electronic health record data from 71 US health systems, we examined quarterly trends in utilization of different advanced therapies in patients with ulcerative colitis and Crohn’s disease between 2021 and 2025, using interrupted time-series analysis utilizing Prais–Winsten regression. Results In 11 093 patients with ulcerative colitis treated with advanced therapies, we observed an increase in use of upadacitinib (12.1% in Q2/2025; P < .001, compared with first quarter of prescription), interleukin-23p19 (IL23p19) antagonists (5.5%; P = .03), and ustekinumab (9.5%; P = .04), decline in use of tumor necrosis factor (TNF) antagonists (34.5%; P = .003), and stable use of vedolizumab (33.6%; P = .17) and sphingosine-1 phosphate receptor modulators (1.6%; P = .28). In 15 951 patients with Crohn’s disease treated with advanced therapies, we observed an increase in use of IL23p19 antagonists (15.0% in Q1/2025; P = .003) and upadacitinib (5.9%; P < .001) and decline in use of TNF antagonists (50.2%; P = .001) and ustekinumab (13.5%; P < .001). Conclusions Contemporary trends in advanced therapy utilization in patients with IBD suggest an increased utilization of upadacitinib and anti-interleukins, accompanied by a decline in use of TNF antagonists in the USA.

ABSTRACT Background Advanced therapies increase the risk of shingles in inflammatory bowel diseases (IBD). Aim To compare the risk of shingles with different advanced therapies in patients with IBD. Methods We identified patients with IBD who initiated treatment with tumour necrosis factor (TNF) antagonists, anti‐integrins, anti‐interleukins, Janus kinase (JAK) inhibitors, or sphingosine‐1 phosphate receptor (S1PR) modulators between 2016 and 2022 and had follow‐up for at least 1 year before and after treatment initiation. We estimated the incidence rate (IR per 100 person‐year [PY]) of shingles (overall and complicated) and compared the risk with different advanced therapies through multinomial propensity score‐based inverse probability of treatment weighting (IPTW), with propensity scores estimated through generalised boosted models, accounting for disease characteristics, healthcare utilisation, comorbidities and prior and concomitant medications. Weighted Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for multiple treatment comparisons. Results We included 21,675 patients followed over 27 months. IRs per 100 PY of shingles and complicated shingles were: TNF antagonists 1.0/0.3, anti‐integrin agents 1.4/0.4, anti‐interleukins 1.2/0.5, JAK inhibitors 3.3/0.9 and S1PR modulators 2.0/1.0. After adjusting for confounding variables, JAK inhibitors were associated with higher risks of shingles than TNF antagonists (HR 2.19; 1.28–3.75), anti‐integrins (HR 1.87; 1.12–3.14) and anti‐interleukins (HR 1.70; 0.98–2.96). Conclusions JAK inhibitors were associated with 1.7–2.2‐fold higher risk of shingles than other advanced therapies.

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 .

INTRODUCTION: Current guidelines recommend endoscopic surveillance of Barrett's esophagus (BE) but do not account for competing mortality unrelated to esophageal cancer (EC). We conducted a systematic review and meta-analysis to estimate EC and non-EC mortality risk in BE patients. METHODS: We searched multiple databases for studies reporting mortality in BE. We included population-based studies providing standardized mortality ratio (SMR). The primary outcome was SMR from all causes and EC and non-EC etiologies. SMR was calculated by dividing the observed mortality over the expected mortality. Logarithmic form of SMRs was pooled using random-effects model. RESULTS: Our search yielded 2,826 articles, of which 7 studies (n = 34,454) were included. All-cause mortality was elevated in BE patients compared with population controls (pooled SMR 1.24, 95% confident interval [CI] 1.01–1.53) driven in part by increased EC mortality risk (SMR 8.98, 95 CI 5.12–15.77). The mortality risk was still increased but attenuated after excluding EC mortality (SMR 1.21, 95% CI 1–1.46). There was no increased mortality risk of non-EC malignancies (SMR 1.22, 95% CI 0.82–1.82) or mortality due to noncancer etiologies (SMR 1.13, 95% CI 0.90–1.43). Death due to cardiovascular diseases was higher in BE (SMR 1.16, 95% CI 1.02–1.33). BE patients were 10 times more likely to die from noncancer etiologies than EC (risk ratio 10.71, 95% CI 5.98–19.16). Subgroup analysis of studies that excluded prevalent EC at baseline (3 studies) also showed increased all-cause (SMR 1.12, 95% CI 1.07–1.18) and EC mortality (SMR 4.7, 95% CI 3.58–6.17) among BE patients. DISCUSSION: BE patients exhibit a higher all-cause mortality, driven in part by risk of EC mortality. A personalized approach to surveillance, mitigating risk of EC while recognizing the broader mortality risks, is warranted.

ABSTRACTBackground and AimsWe aimed to assess the impact of setons on perianal fistula outcomes in patients with perianal fistulising Crohn's disease (PFCD) treated with anti‐TNF therapy.MethodsWe included patients treated with their first anti‐TNF therapy for PFCD after undergoing a pelvic MRI between 2005 and 2022 from 6 North American centres. Our exposure was one or more setons at the time of anti‐TNF therapy. Our primary outcome was major adverse fistula outcome (MAFO), a composite of repeat local surgical intervention, hospitalisation, or faecal diversion for PFCD, and our secondary outcome was fistula remission defined clinically. We used 1:1 cardinality matching and propensity score weighting to control for fistula severity based on centrally read MRIs, luminal characteristics, and concomitant therapies.ResultsOur analysis included 221 patients: 81 with setons and 140 without setons. After cardinality matching, our cohorts were balanced (standardised difference < 0.1 for all covariates). Patients with setons had similar rates of MAFO (HR 1.23; 95% CI, 0.68–2.21) and fistula remission at 6 months (OR, 0.81; 95% CI, 0.41–1.59) and 12 months (OR, 0.63; 95% CI, 0.31–1.27) compared to patients without setons. Our results remained stable when analysed by propensity score weighting and in a sensitivity analysis of patients who underwent an exam under anaesthesia. In patients with abscesses, there were lower rates of MAFO (HR, 0.49; 95% CI, 0.19–1.25) but not statistically significant in patients with setons.ConclusionsIn this multicentre, setons were not associated with improved fistula outcomes. Future prospective controlled studies are warranted.

Abstract Background and Aims Over 10% of patients with Crohn’s disease require permanent ileostomy. We aimed to summarize the existing data on diagnosis, definitions of recurrence, and management of Crohn’s disease patients with permanent ileostomy. Methods MEDLINE, Embase, and CENTRAL databases were searched from inception to February 6, 2024. Randomized controlled trials, cohort and cross-sectional studies, and case series of more than 5 patients reporting on postoperative recurrence or the need for surgery in patients with Crohn’s disease and permanent ileostomy were included. Search results were independently screened, and full text of all titles meeting eligibility criteria was obtained. Outcomes of interest included diagnostic techniques, recurrence definitions, and management approaches. We estimated pooled rates (with 95% confidence interval [CI]) of recurrence. Results Thirty cohort studies including 2055 Crohn’s patients with permanent ileostomy were included (53% female, median age at the time of ileostomy creation 32 years, the most common reason for ileostomy was refractory disease). The postoperative recurrence rate was 27% (95% CI, 21.3–33.3, 26 studies, 451/1805 patients). Modalities for diagnosis of Crohn’s disease recurrence were symptoms (15 studies), endoscopy (4 studies), histology from endoscopic biopsies (2 studies), imaging (5 studies), and surgery (22 studies). The reported definitions of recurrence for each modality were heterogeneous. Conclusions There is a lack of standardized monitoring tools and criteria for diagnosing recurrence in patients with Crohn’s disease and permanent ileostomy. The results of this systematic review will form the basis of a global expert recommendation exercise focused on developing management standards and trial endpoints for this condition.