Background:Inflammatory bowel disease (IBD) has significantly increased over the past two decades. However, registries in Latin America remain scarce, prompting the creation of the Colombian pediatric IBD registry for patients under 18 years of age, designed as a continuous and periodically assessed database. Methods:A descriptive, longitudinal, ambispective, and multicenter observational study was conducted in children aged 0-18 years between January 1999 and December 2021. The analysis was performed based on the age of onset (Paris classification), with subdivisions for very early onset and phenotypes using the Pediatric IBD-classes algorithm. Data were collected in REDCap and analyzed with STATA 15.1. Results:A total of 209 patients were included, 54.5% male. The median age at diagnosis was 12.3 years (IQR 8.5-14.6). Phenotype distribution included: 104 (53.06%) typical ulcerative colitis (TUC), 52 (26.53%) Crohn's disease (CD), 18 (9.18%) unclassifiable IBD (U-IBD), 11 (5.61%) colonic Crohn's disease (CCD), and 11 (5.61%) atypical ulcerative colitis (AUC). The median time to diagnosis was 6.6 months, and treatment began after a median of 11.2 days. Coffee-cultivation zone 39%. Extraintestinal manifestations were reported in 43.9% of cases. Initial treatments included mesalamine ± steroids (35.86%), immunomodulators ± steroids (32%), exclusive/partial enteral nutrition (11.41%), and biologics ± immunomodulators (20.65%), which increased to 57.7% during follow-up. Relapse occurred in 53.26% of patients, while 35.32% achieved remission. Conclusions:This registry highlights the increasing incidence of pediatric IBD in Latin America, providing valuable insights into clinical presentations, diagnostic delays, treatment strategies, and outcomes, while revealing regional and global disparities.
Background:Tofacitinib is an oral Janus kinase inhibitor used for the treatment of ulcerative colitis. This study evaluated efficacy/safety of dose reduction to tofacitinib 5 mg twice daily (BID) versus remaining on 10 mg BID in patients in stable remission on 10 mg BID. Methods:RIVETING, a phase 3b/4, double-blind, randomized, parallel-group trial, enrolled patients in stable remission (≥6 months) and corticosteroid-free (≥4 weeks) who received tofacitinib 10 mg BID for ≥2 years. Efficacy was reported to month (M)30 and safety was reported throughout. Results:One hundred and forty patients were randomized (1:1) to tofacitinib 5 or 10 mg BID; 50.0% and 62.9%, respectively, maintained modified Mayo score remission at M30. Remission rate differences at M30 between doses were generally greater in patients with a baseline endoscopic subscore of 1 versus 0, and with versus without tumor necrosis factor inhibitor (TNFi) failure. 11/14 patients who dose-escalated from 5 to 10 mg BID following relapse recaptured remission (median 4.8 months). Serious infection and herpes zoster incidence rates were numerically higher with tofacitinib 10 versus 5 mg BID; overall, adverse event rates were generally similar between doses. Conclusions:Patients on tofacitinib 10 mg BID generally maintained modified Mayo score remission through M30 after reduction to 5 mg BID; most patients who relapsed recaptured remission after dose-escalating back to 10 mg BID. Efficacy was more likely to be maintained following dose reduction in patients with baseline endoscopic subscore 0 versus 1, without versus with prior TNFi failure. Serious infection and herpes zoster incidence was higher with tofacitinib 10 versus 5 mg BID, consistent with known safety profile. ClinicalTrialsgov:NCT03281304.
Background:Complications such as intermittent pouchitis (IP) and chronic inflammatory disorders of the pouch (CP) are common after ileal pouch-anal anastomosis (IPAA), particularly among patients with both ulcerative colitis and primary sclerosing cholangitis (PSC). There are no standardized approaches for prophylaxis against these complications for patients with PSC undergoing IPAA. We compared outcomes among patients with PSC and IPAA who received antibiotic or immunosuppressive therapies to those who did not. Methods:We designed a retrospective cohort study that included patients with ulcerative colitis and PSC from 7 tertiary care centers that underwent IPAA between 1994 and 2023. Patients were categorized on whether they received medications following IPAA that may provide primary prophylactic benefit, such as antibiotics, probiotics, immunomodulators, or biologic medications; and the proportion of patients developing IP and CP was evaluated. Results:A total of 172 patients were included in the cohort, and 13 (7.6%) patients received antibiotics or immunosuppressant medications. Antibiotics and probiotics were the most common therapy (5 patients, 2.9%), followed by biologics, small-molecule inhibitors, immunomodulators, or mesalamine (all 1 patient, 0.6%). Compared to patients not receiving antibiotics or immunosuppression, patients receiving antibiotics or immunosuppression were significantly less likely to develop IP (69.2% vs 91.2%; P = .03; odds ratio 0.22; 95% CI, 0.06-0.80) and CP (23.1% vs 56.0%, P = 0.04; OR 0.24, 95% CI, 0.06-0.89). Conclusions:In this retrospective cohort of patients with ulcerative colitis and PSC undergoing IPAA, usage of concomitant antibiotics or immunosuppression was low. However, use of concomitant antibiotics or immunosuppression may decrease the burden of inflammatory conditions of the pouch in these high-risk patients.
Background:In hospitalized patients with ulcerative colitis (UC), timely endoscopy may be constrained. We evaluated whether the inflammatory burden index (IBI; C-reactive protein × neutrophil-to-lymphocyte ratio [CRP×NLR]) is associated with endoscopic activity. Methods:We retrospectively studied adults hospitalized with UC between 2023 and 2025 who underwent index lower endoscopy during the same admission, with blood sampling within 24 hours of admission and endoscopy within 72 hours of admission. Endoscopic activity was graded by Mayo Endoscopic Subscore (MES) and dichotomized as MES 0-1 versus ≥2. Associations with MES ≥2 were examined using logistic regression with adjustment for age, sex, and body mass index, with IBI modeled as log(IBI + 1). Discrimination was assessed by receiver operating characteristic analysis with same-sample DeLong testing. Sensitivity analyses were restricted to endoscopy within 48 hours after blood sampling. Results:Among 107 patients, 83 (77.6%) had MES ≥2. IBI correlated with MES (ρ = 0.58; P < .001) and remained independently associated with MES ≥2 (adjusted OR, 5.28; 95% CI, 2.12-13.14; P < .001). Discrimination was reasonable (AUC, 0.83; 95% CI, 0.76-0.90). CRP alone performed similarly (AUC, 0.80; 95% CI, 0.71-0.88; P = .227 vs IBI), as did a CRP+NLR model (AUC, 0.84; 95% CI, 0.77-0.91; P = .40 vs IBI). Findings were directionally consistent in the ≤48-hour sensitivity analysis. The Youden-derived IBI cutoff was 3.65 (sensitivity, 72.3%; specificity, 91.7%) and should be considered exploratory. Conclusions:In this cohort, IBI was associated with moderate-to-severe endoscopic activity. Performance was comparable to CRP alone, and findings should be interpreted as exploratory rather than as evidence for a standalone clinical decision tool.
Background:Crohn's disease (CD) patients achieving deep remission, defined as clinical remission with endoscopic healing (EH), have a lower rate of CD-related adverse events. EH can be achieved with anti-tumor necrosis factor (TNF) dose optimizations directed by pharmacokinetic (PK) and pharmacodynamic (PD) biomarkers. The primary aim was to identify PK metrics and PD biomarker cut-points associated with EH. Methods:In this multicenter, cross-sectional study, we enrolled CD patients (age 1-22 years) who received an anti-TNF biologic (infliximab or adalimumab) for >6 months and underwent ileocolonoscopy. EH was defined as a simple endoscopic score-CD (SES-CD) < 3. Results:Eighty-seven patients were enrolled with EH found in 55.2%. Lower levels of novel biomarkers neutrophil CD64, monocyte CD64, and soluble CD64 were associated with EH with cut-points of <4.5 ratio (AUROC 0.76), <44.6 ratio (AUROC 0.67), and <15.9 ng/mL (AUROC 0.67), respectively. There was no difference in the mean trough concentrations of infliximab or adalimumab between EH and non-EH, but the median infliximab clearance was higher in non-EH (0.26 L/day) compared to EH (0.21 L/day, P = .02). In our infliximab multivariable model, slower infliximab clearance, lower platelet count, and higher serum albumin were strong predictors for EH (AUC 0.90). Conclusions:We identified novel PK and PD cut-points for biomarkers associated with EH, including infliximab clearance and the novel CD64 biomarkers. Furthermore, we developed a multivariable PK and PD model for EH that, following validation, could guide dose escalation (PK failures) or prompt a switch to an alternate advanced therapeutic for PD failures.
