Background/Objectives: Cytomegalovirus (CMV) is an opportunistic pathogen, complicating acute severe ulcerative colitis (ASUC), and its role in ASUC prognosis remains a debate. This study aims to report the rates and identify predictors for colectomy at 12 months, following an episode of ASUC with concomitant CMV colonic infection. Methods: This is a retrospective cohort study of patients with ASUC and CMV colonic infection confirmed by PCR or Immunohistochemistry. Baseline clinical, biochemical, endoscopic and disease-related characteristics were recorded. Patients were followed-up for 12 months to calculate the one-year colectomy rate. Predictors of colectomy were identified via multivariate logistic regression. Results: Forty-five cases of CMV colonic infection in 37 patients with ASUC were recorded [66.7% men, mean age: 47.0 years (SD = 18.5)]. At diagnosis, 20% were on monotherapy with advanced treatment and 37.8% on advanced treatment plus corticosteroids and/or immunomodulators. Twenty-three (51.1%) were receiving corticosteroids, while 17.8% did not receive any immunosuppressive agent. Forty (88.9%) patients were treated with ganciclovir and valganciclovir and one (2.2%) with foscarnet for at least 21 days. Eleven patients (24.4%) required colectomy, two (4.4%) during their initial hospitalization and nine (20%) during the follow-up period. The recurrence of CMV was recorded in nine (20.9%) cases, three of which required colectomy. Patients with hemoglobin < 12 g/dL (p = 0.023) and patients on vedolizumab at diagnosis (p = 0.050) had a higher probability of colectomy. Conclusions: We report a 25% one-year colectomy rate in our cohort with ASUC and superimposed CMV colonic infection. At baseline, anemia and vedolizumab treatment were associated with a higher probability of colectomy.

Upadacitinib is a selective Janus kinase-1 inhibitor, approved for the management of Crohn’s disease (CD) by the United States Food & Drug Administration. In Greece, upadacitinib was initially available through an early-access program. Our goal was to describe the real practice experience. This was a multicenter retrospective cohort study of patients with moderate-to-severe CD. The primary endpoint was clinical response, defined as a reduction ≥3 in the Harvey-Bradshaw index. Secondary endpoints included biochemical improvement. Outcomes were assessed at 4, 8 and 12 weeks. A total of 24 CD patients received upadacitinib and were included in the analysis. Their mean age was 42.2 years (range 24-63). Eleven patients (45.8%) had ileocolonic CD and 5 (20.8%) CD colitis. Fourteen patients had active extraintestinal manifestations. The majority of patients (19/24) had ≥3 failed biologics. All of them had failed treatment with anti-tumor necrosis factor and 19 (79%) with ustekinumab. At 12 weeks, nearly all patients achieved a clinical response (85%). Of 13 patients with C-reactive protein >5 mg/L at baseline, 11 (84.6%) achieved normalization by week 8. Adverse events occurred in 3 patients (14.2%). In a small cohort of resistant CD patients, the short-term clinical efficacy of upadacitinib was high.

Background/Objectives: Ustekinumab has been approved for the treatment of moderate to severe ulcerative colitis. Real-world data regarding its efficacy and the discovery of predictive factors of response need to be studied further. We aimed to evaluate the efficacy and identify predictors of response to induction treatment with ustekinumab in patients with ulcerative colitis. Methods: This is a multicenter, prospective cohort study. Clinical response (CR) at week 16 was the primary endpoint, and steroid-free clinical remission (SFCRem) and endoscopic response were the secondary endpoints. Baseline histology, mucosal gene expression, and pharmacokinetics were studied for their effect on response to treatment. Results: We included 123 patients (mean age = 50.3 years). CR was recorded in 70.8% (75/106), SFCRem in 48% (59/123), endoscopic improvement in 71.4% (40/56), and mucosal healing in 28.6% (16/56). Higher PRO-stool frequency (OR = 0.49, p = 0.027), concomitant use of 5-ASA (OR = 3.69, p = 0.021), platelet number of ≥284 × 10⁹/L (OR = 6.52, p = 0.001) at baseline, and a drop in the total count of platelets by 10⁸/L (OR = 1.23, p = 0.022) at week 8 were independently associated with CR. Elevated trough levels of ustekinumab at week 16 were associated with a higher probability of endoscopic improvement (median difference = 3784 ng/mL, p = 0.013), with an optimal cut-off value of 3500 ng/mL (AUC = 0.82, 95% CI: 0.66–0.96). Increased mucosal mRNA expression for IL-23 (p = 0.007) and IL-23R (p = 0.031) at baseline was associated with increased probability of CR. Higher continuous Geboes scores at baseline were associated with a lower probability of CR (OR = 0.80, p = 0.045), with an optimal cut-off value of 14 (AUC = 0.75, 95% CI: 0.57–0.93). Conclusions: Clinical, laboratory, and molecular markers may identify patients with ulcerative colitis who are more likely to respond to ustekinumab.