Aim: To evaluate outcomes of early dose optimization of golimumab in ulcerative colitis (UC) patients with inadequate response to golimumab induction treatment. Methods: This observational, multicenter, cohort study included patients with moderate-to-severe active UC and with inadequate response to subcutaneous golimumab induction doses, in whom weight-based golimumab maintenance dose (European labelling) of 50 mg every-4-weeks (q4wk) was optimized before week 14 to 100 mg q4wk. At week 14, we assessed clinical response and remission using the partial Mayo score. In the long-term we evaluate the cumulative probabilities of golimumab failure-free survival and colectomy-free survival. Results: A total of 209 patients who received golimumab induction doses were eligible. Of these, 151 patients (72.2%) weighing less than 80 kg were assigned to golimumab maintenance dose of 50 mg q4wk. Twenty-four patients (15.9% [12.5% overall]), in whom scheduled doses of 50 mg q4wk were optimized to 100 mg q4wk before week 14 compose the study population. At week 14, 16 patients (66.7%, 95% CI 45.7-87.6) had clinical response, of these 12 were corticosteroid-free. Four patients (16.7%) achieved corticosteroid-free remission. After a median follow-up of 12 months (IQR 10-22), 13 patients (54.2%) maintained clinical benefit. Thirteen of 16 patients (81.2%) with clinical response at week 14 maintained clinical benefit at last follow-up. All patients avoided colectomy. In none of the patients golimumab dose was de-escalated. There were no adverse events leading to golimumab withdrawal. Conclusion: Early optimization of golimumab dose induces clinical response at week 14 in two thirds of UC patients and leads to long-term clinical benefit in over half of patients.

Background/Objectives: Evidence is needed on the real-world outcomes of upadacitinib in patients with ulcerative colitis. This systematic review and meta-analysis evaluated the real-world effectiveness of upadacitinib for active UC. Methods: The primary outcome was clinical remission evaluated at week 8. Secondary outcomes included response, steroid-free remission, biochemical remission, colectomy, and safety. A random-effects meta-analysis model was used to calculate the pooled effect sizes (percentages or incidence rates) of effectiveness and safety outcomes. Results: Twenty-four studies with 1388 patients were included. Ninety-four percent of patients had previously failed biologics or Janus kinase inhibitors (JAKi), including 53.2% with tofacitinib. Clinical remission at week 8 was achieved in 68.4% of patients (95% confidence interval 55.5–80.2). Clinical remission was achieved in 48.3%, 71.1%, and 64.6% of patients at weeks 2 to 6, 12 to 16, and 24 to 36, respectively. Response was achieved in 72.6%, 82.1%, and 78.7% of patients at weeks 2 to 6, week 8, and weeks 12 to 16, respectively. Steroid-free remission was achieved in 39% of patients at week 8. Upadacitinib results were unaffected by prior biologic or JAKi failure. Mean fecal calprotectin level decreased from 1485.0 µ/g at baseline to 454.8 µ/g post-treatment (p < 0.01). The mean CRP level decreased from 12.3 mg/L at baseline to 4.4 mg/L post-treatment (p = 0.02). The incidence rates of colectomy, serious adverse events, and herpes zoster were 13.3, 2.3, and 1.7 per 100 patient-years, respectively. Conclusions: This meta-analysis confirms the effectiveness and safety of upadacitinib in a highly treatment-refractory population of UC patients.

Background: Local injection of darvadstrocel, a suspension of expanded adipose‐derived allogenic mesenchymal stem cells, has been used for treatment‐refractory perianal fistulas in Crohn's disease (CD).Objective: This study aimed to investigate efficacy and safety of darvadstrocel for complex perianal fistulas in CD.Methods: A systematic search was conducted through April 2024 in relevant databases for observational studies evaluating darvadstrocel. A random‐effects meta‐analysis model was used to calculate the pooled effect sizes (proportions or incidence rates [IRs]) with 95% confidence intervals (CIs) of effectiveness and safety outcomes. The risk of bias was evaluated using the Joanna Briggs Institute Critical Appraisal Tool. The I² value assessed heterogeneity. Sensitivity and subgroup analyses were also conducted.Results: Twelve studies were included with 595 patients. The pooled rate of patients achieving clinical remission, defined as fistula healing, was 68.1% at month 6 (95% CI 63.4–72.7) and 77.2% (95% CI 70.1–83.8) at month 12. Combined remission, defined as clinical remission and absence of collections >2 cm confirmed by magnetic resonance imaging, was reported in 60.6% and in 69.7% of patients at months 6 and 12, respectively. The rate of patients with treatment failure, defined as no clinical remission at the last follow‐up (mean 18.7 months; SD 9.9), was 34.5%. Failure rate was independent of follow‐up time (p = 0.85). For effectiveness outcomes, between‐study heterogeneity was negligible. Subgroup analysis indicated that none of the covariates modified the treatment effect. Pooled IRs per 100 patient‐years of adverse events (AE), serious AEs, perianal abscesses, and reoperations were 19.6, 3.2, 16.9 and 7.1, respectively.Conclusion: Evidence from observational studies supports the efficacy and safety of darvadstrocel for complex perianal fistulas in CD. Studies have reported high fistula healing rates that can be sustained long‐term in most patients, with negligible between‐study heterogeneity, as well as a favorable safety profile.

Background: A causal relationship between Crohn's disease (CD) and asthma is reported, but the underlying mechanisms are not fully understood. We sought to investigate the role of IgE and IgE‐mediated pathways in the pathophysiology of CD. Methods: 20 CD patients, 10 allergic patients without inflammatory bowel disease, and 10 healthy donors (HD) were included in the study. Total serum IgE was quantified by ELISA. Circulating IgE ⁺ and FcεRIα ⁺ immune cells, as well as specific CD4 ⁺ T cell populations, were determined by flow cytometry. Gene set enrichment signatures from available single‐cell (sc)RNAseq datasets of the intestine from CD patients were analyzed. Purified plasmacytoid dendritic cells (pDCs) from CD patients were cocultured with naïve CD4 ⁺ T cells to assess Tregs generation. Results: CD patients, similar to allergic non‐CD patients, displayed significantly higher numbers of circulating IgE ⁺ or FcεRIα ⁺ immune cells than HD. The percentage of blood IgE ⁺ or FcεRIα ⁺ pDCs was significantly higher in CD than HD and similar to allergic non‐CD patients. CD patients showed significantly higher numbers of effector memory CD4 ⁺ T cells and lower numbers of FOXP3 ⁺ Tregs than HD. scRNAseq data from CD patients confirmed that Tregs imbalance and overactivation of IgE‐mediated pathways take place also in gut tissues of children and adults, suggesting IgE could interfere in the pDC‐Tregs axis. In vitro functional experiments demonstrated that IgE‐crosslinking on pDCs from CD patients impairs Treg generation, which was restored by the anti‐IgE mAb omalizumab. Conclusions: IgE might play an unprecedented role in CD by impairing the capacity of pDCs to generate Tregs, which could represent a novel mechanism contributing to CD to be exploited for alternative therapeutic interventions.