Eileen Crowley

Background: Crohn’s disease (CD) is an inflammatory bowel disease (IBD) that can affect any part of the gastrointestinal tract. Although upper gastrointestinal (UGI) manifestations are well recognized in pediatrics, UGI-CD in adults has historically been underestimated. Methodological limitations, including selective endoscopy and inconsistent classification, have contributed to variable prevalence estimates. Aims: Our goals were to summarize the prevalence of UGI-CD in adults with CD, understand demographic variations, and summarize knowledge gaps. Methods: We conducted a scoping review of MEDLINE, Embase, and Cochrane CENTRAL (1995–November 2025) using PRISMA-ScR and JBI methodology. Eligible studies reported adult UGI-CD prevalence or related epidemiologic data. Extracted variables included prevalence estimates, site-level involvement, and demographics. Systematic reviews were included to summarize review-level epidemiologic evidence. Results: In total, 117 primary studies and eight systematic reviews were included. Across 95 cohorts with prevalence data, the median prevalence of UGI-CD was 8.8% (IQR 3.99%-14.5%). Higher rates were observed in cohorts using systematic endoscopy and biopsy, while population-based cohorts reported lower values. Isolated UGI-CD was rare, with a median prevalence of 1.37% (IQR 0.87%-3.02%). Prevalence varied geographically and ethnically, with lowest rates in South Asian cohorts and higher rates in East Asian and Middle Eastern cohorts. Site-specific reporting was inconsistent, and few studies detailed modifiers such as smoking or family history. Conclusions: Reported prevalence estimates of adult UGI-CD remain highly variable due to inconsistent definitions and detection strategies. Standardized, site-specific adult definitions and systematic diagnostic protocols are needed to enable cross-study comparisons and thus improve prevalence estimates and address demographic reporting gaps.

Background and Aims: Despite considerable advancements in the therapeutic landscape of inflammatory bowel disease (IBD) for adults, long delays exist for paediatric IBD (pIBD) approval, with a median delay of >7 years following adult approval. Our aim is to summarise the landscape of pIBD clinical trials through a review of trial registries. Methods: We conducted a cross-sectional review of ClinicalTrials.gov and ClinicalTrialsRegister.eu to identify investigational and approved therapeutic agents for the treatment of pIBD. All interventional studies involving pIBD (aged n = 39), infliximab, adalimumab, golimumab, and ustekinumab, and investigational therapies ( n = 42) such as vedolizumab, guselkumab, mirikizumab, risankizumab, duvakitug, afimkibart, and tulisokibart. Nine completed and 11 active trials assess small molecule therapies, including tofacitinib, upadacitinib, filgotinib, etrasimod, ozanimod, and obefazimod. Conclusions: Efforts to expedite approval of new agents in pIBD are warranted to ensure timely access to effective medications. Consideration for novel trial designs alongside continued engagement with regulatory bodies, sponsors, and the academic pIBD community is essential to advance drug approvals for pIBD.

Background: Crohn’s disease (CD) is characterized by transmural inflammation, and achieving transmural healing (TH), may lead to improved long-term outcomes. However, evidence supporting this hypothesis is limited. Methods: Adult patients diagnosed with CD who underwent ileocolonoscopy and cross-sectional imaging within 6 months were included. Long-term outcomes of CD-related surgery and hospitalization in patients with TH, endoscopic healing (EH) alone, radiologic healing (RH) alone, and no healing (NH) were assessed. We used Cox proportional hazards models and modified Poisson regression. Results: Among 180 included patients, 26.7% achieved TH, 21.1% achieved EH, 12.8% achieved RH, and 39.4% were classified as NH. At baseline, 54.4% were on biologics which increased to 81.7% at last follow-up (76-78 months across groups). Cumulative probabilities of surgery were lowest in patients with TH (0%, 2.3%, 7.0% at 1, 3, and 5 years) and highest in patients with NH (13%, 20.5%, and 26.9%, respectively) (P = .03). On Cox proportional hazard regression analysis, TH was associated with a significantly reduced risk of CD-related surgery (hazard ratio, 0.01; 95% confidence interval, 0.00-0.35; P = .009) compared with NH. The probabilities of surgery were lower for patients with RH compared with EH (10% vs 13.2%, 10% vs 18.4%, and 21.2% vs 26.9% at 1, 3, and 5 years) but were not statistically significant (P = .41). Probabilities of CD-related hospitalization were lowest with TH (4.3%, 8.8%, and 13.6% at 1, 3 and 5 years) but were not statistically different than other healing categories (P = .67). Conclusions: TH was associated with superior long-term outcomes compared with EH or RH alone. Future studies should focus on standardizing its definition and evaluate treat-to-target strategies.

Impaired linear growth is a common, clinically meaningful complication of paediatric inflammatory bowel disease (IBD), particularly Crohn's disease, arising from the combination of chronic intestinal inflammation, undernutrition, dysfunction of the growth hormone–insulin‐like growth factor‐1 axis, and iatrogenic effects such as glucocorticoid exposure. Up to one in five children exhibit short stature at diagnosis, with higher risk in pre/early‐pubertal onset, small‐bowel involvement, persistent activity, and high cumulative steroid use. Although most patients ultimately achieve adult height close to their genetic potential, preventable height loss still occurs in vulnerable subgroups. Effective control of intestinal inflammation remains central to restoring growth velocity and IGF‐1 bioactivity. Specific nutritional strategies, including exclusive enteral nutrition and the Crohn's Disease Exclusion Diet with partial enteral nutrition, or anti‐TNF therapy are steroid‐sparing options that induce remission and support short‐term weight gain. Individualized energy and protein support, alongside vigilant correction of iron, vitamin D, and zinc deficiencies, is essential, and bone health requires proactive assessment in those with low BMI/height z‐scores or steroid exposure. Routine longitudinal monitoring of height, weight, BMI, and pubertal staging should be embedded as explicit treat‐to‐target outcomes, with early escalation to effective maintenance therapy when growth targets are unmet. Growth hormone therapy has a limited, adjunctive role and should be reserved for exceptional, refractory growth failure after optimization of disease control and nutrition within a multidisciplinary framework. Integrating growth and pubertal progression into standard paediatric IBD care can minimize irreversible deficits and improve lifelong skeletal and psychosocial outcomes.

Background: Immune-mediated extraintestinal manifestations (IM-EIMs) are common in paediatric inflammatory bowel disease (pIBD). This systematic review and meta-analysis aimed to summarise the incidence and prevalence of IM-EIMs in pIBD. Methods: MEDLINE, EMBASE, CENTRAL and clinicaltrials.gov were searched up to May 6, 2024, for studies that included pIBD (2-17 years) patients diagnosed with IM-EIMs. Primary outcomes included the incidence and prevalence of IM-EIMs among pIBD. Meta-analysis included pooled proportions of prevalence with DerSimonian-Laird random-effects analysis. Results: The pooled proportion of IM-EIMs among pIBD overall was 10% (95% CI, 8-12%; I2=97.2%) among 65 studies (35,343 patients). The pooled proportion of IM-EIMs was 10% (95% CI, 7-13%; I2=94.8%) among 37 Crohn’s disease (CD) studies (7657 patients), compared to 11% (95% CI, 7-15%; I2=93.3%) among 39 ulcerative colitis (UC) studies (4698 patients). Enthesitis was the highest reported individual IM-EIM (23%, 95% CI, 4-50%; I2=94.7%) in pIBD. Arthritis was the second highest reported individual IM-EIM (8%, 95% CI, 6-10%; I2=96%) in pIBD, followed by primary sclerosing cholangitis (PSC) in UC (5%, 95% CI, 4-7%; I2=81%). Uveitis, pyoderma gangrenosum, autoimmune hepatitis and PSC in CD were the lowest reported IM-EIMs at 1% or less. The largest difference in proportions between IBD phenotypes was PSC, which was 4% higher in UC than CD. Conclusions: While musculoskeletal manifestations are common, fewer than 5% of pIBD patients experience ophthalmological, dermatological, and liver IM-EIMs. The small number of studies resulted in significant methodological and statistical heterogeneity. Multicentre collaborative efforts are needed to systematically describe the epidemiology of IM-EIMs in pIBD.

Ustekinumab dosing information for pediatric Crohn’s disease (CD) is limited. To examine ustekinumab pharmacokinetic and effectiveness data in a largely bio-naïve cohort, focusing on early (week 8) levels. Children in the prospective Canadian Children IBD Network initiating intravenous (IV) ustekinumab for CD with a week 8 level were evaluated. Disease activity was assessed by corticosteroid-free clinical remission (CSFR), biochemical CSFR, and mucosal healing (MH) by colonoscopy or fecal calprotectin 2) was greater than for those ≥40kg (median 6.1 [5.4-6.5] mg/kg; 218 ([78-237] mg/m², P < .001). However, week 8 levels were similar (P = .26). This was most striking in those with low albumin. Of 34/58 (59%) without escalation to 4 weekly dosing, 43%, 35%, and 19% exhibited CSFR, biochemical CSFR, and MH, respectively, during established maintenance. Median week 8 levels were roughly 5-6 µg/g vs 7-10 µg/g in patients not achieving vs achieving favorable outcomes, while ROC analysis indicated levels 8-9 µg/mL were associated with improved outcomes. Children 2) to achieve similar week 8 levels as children ≥40kg receiving conventional adult 6 mg/kg weight-tiered induction. Higher week 8 levels were associated with favorable later outcomes.

Background: The incidence of pediatric-onset inflammatory bowel disease (IBD) and the costs of caring for individuals with IBD are both increasing. We calculated the direct healthcare costs of pediatric IBD in the first year after diagnosis and developed a model to predict children who would have high costs (top 25th percentile). Methods: Using data from the Canadian Children IBD Network inception cohort (≤16 years of age, diagnosed between 2013 and 2019) deterministically linked to health administrative data from Ontario, Canada, we estimated direct healthcare and medication costs accrued between 31 and 365 days after diagnosis. Candidate predictors included age at diagnosis, sex, rural/urban residence location, distance to pediatric center, neighborhood income quintile, IBD type, initial therapy, disease activity, diagnostic delay, health services utilization or surgery around diagnosis, regular primary care provider, and receipt of mental health care. Logistic regression with stepwise elimination was used for model building; 5-fold nested cross-validation optimized and improved model accuracy while limiting overfitting. Results: The mean cost among 487 children with IBD was CA$15 168 ± 15 305. Initial treatment (anti-tumor necrosis factor therapy, aminosalicylates, or systemic steroids), having a mental health care encounter, undergoing surgery, emergency department visit at diagnosis, sex, and age were predictors of increased costs, while having a regular primary care provider was a predictor of decreased costs. The C-statistic for our model was 0.71. Conclusions: The cost of caring for children with IBD in the first year after diagnosis is immense and can be predicted based on characteristics at diagnosis. Efforts that mitigate rising costs without compromising quality of care are needed.

Background: Patients with inflammatory bowel disease (IBD) exhibit considerable interindividual variability in medication response, highlighting the need for precision medicine approaches to optimize and tailor treatment. Pharmacogenetics (PGx) offers the ability to individualize dosing by examining genetic factors underlying the metabolism of medications such as thiopurines. Pharmacogenetic testing can identify individuals who may be at risk for thiopurine dose-dependent adverse reactions including myelosuppression. We aimed to evaluate PGx variation in genes supported by clinical guidelines that inform dosing of thiopurines and characterize differences in the distribution of actionable PGx variation among diverse ancestral groups. Methods: Pharmacogenetic variation in TPMT and NUDT15 was captured by genome-wide genotyping of 1083 pediatric IBD patients from a diverse Canadian cohort. Genetic ancestry was inferred using principal component analysis. The proportion of PGx variation and associated metabolizer status phenotypes was compared across 5 genetic ancestral groups within the cohort (Admixed American, African, East Asian, European, and South Asian) and to prior global estimates from corresponding populations. Results: Collectively, 11% of the cohort was categorized as intermediate or poor metabolizers of thiopurines, which would warrant a significant dose reduction or selection of alternate therapy. Clinically actionable variation in TPMT was more prevalent in participants of European and Admixed American/Latino ancestry (8.7% and 7.5%, respectively), whereas variation in NUDT15 was more prevalent in participants of East Asian and Admixed American/Latino ancestry (16% and 15% respectively). Conclusions: These findings demonstrate the considerable interpopulation variability in PGx variation underlying thiopurine metabolism, which should be factored into testing diverse patient populations.