Evanthia Zampeli

Background and Objectives: Ozanimod is approved for the treatment of ulcerative colitis (UC). The aim of the present study was to evaluate the clinical, biochemical, and endoscopic outcomes. Materials and Methods: This was a retrospective, multicenter, cohort study. Clinical, biochemical, endoscopic, and safety data were collected from medical records. Τhe primary outcome was clinical response at week 12. Secondary outcomes included clinical remission, endoscopic improvement and remission, biochemical outcomes, treatment persistence, and safety. Clinical outcomes were assessed at weeks 12 and 48, while treatment persistence was evaluated over the complete 48-week follow-up period, using Kaplan–Meier analysis. Clinical response was defined as a ≥30% reduction in partial Mayo score and remission as a partial Mayo score < 3, with no individual sub-score > 1 and a rectal bleeding sub-score of 0. Clinical response and remission were primarily assessed using an observed-case approach, with an additional sensitivity analysis classifying discontinuations due to lack of efficacy as treatment failures. Results: A total of 79 patients were included (62.0% male; median age 44 years, IQR 31–56). Prior biologic exposure was recorded in 29.1%, and 64.6% were previously exposed to oral corticosteroids. Among patients with available clinical assessment at week 12 (n = 62), clinical response and clinical remission were achieved in 77.4% and 71.0%, respectively. Among patients with available data at week 12 (n = 32), endoscopic improvement was observed in 65.6%, while endoscopic remission was achieved in 15.6%. At week 48, among 26 evaluable patients, clinical response and remission rates were 96.2% and 84.6%, respectively; when discontinuations due to lack of efficacy were considered treatment failures, the corresponding rates were 52.1% and 45.8%. Treatment persistence did not differ significantly according to overall prior biologic exposure, whereas previous vedolizumab exposure was associated with lower treatment persistence over the week 48 follow-up (log-rank p = 0.037). In multivariable Cox regression, previous vedolizumab exposure remained associated with an increased hazard of treatment discontinuation (adjusted HR 3.07, 95% CI 1.23–7.67; p = 0.016). Adverse events were reported in 13.9% of patients. Conclusions: Ozanimod demonstrated good efficacy and a favorable safety profile in patients with moderate UC.

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.

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.

Background: Pyoderma gangrenosum (PG) is a rare inflammatory cutaneous disorder that frequently occurs in association with systemic diseases such as inflammatory bowel disease (IBD). This case report describes a 23-year-old female with Crohn’s disease (CD) who developed PG and was successfully treated with adalimumab. The objective of this study is to present the clinical course, treatment approach, and outcomes while reviewing the existing literature on the efficacy of adalimumab in PG management. Methods: A case report is presented, detailing clinical presentation, diagnostic evaluation, and treatment strategy. Additionally, a systematic review was conducted using PubMed to assess studies on adalimumab in PG, focusing on treatment response, remission rates, and adverse effects. Results: The patient presented with ulcerative lesions on her lower extremities and sacroiliitis. After corticosteroid therapy, adalimumab was initiated, leading to significant ulcer healing, reduced back pain, and CD remission. The systematic review identified seven studies on adalimumab in PG. Findings suggest that adalimumab is effective in steroid-refractory cases, with remission achieved in a significant proportion of patients. The most common adverse effects were infections, but overall, adalimumab showed a favorable safety profile. Conclusions: This case highlights the importance of early diagnosis and multidisciplinary management of PG in CD patients. Adalimumab appears to be a promising therapeutic option, particularly for steroid-resistant PG, though further research is needed to establish standardized treatment protocols.

Background: Inflammatory bowel diseases (IBDs), consisting mainly of Crohn’s disease (CD) and ulcerative colitis (UC), are chronic illnesses mainly affecting the gastrointestinal tract, but not only. The role of the human gut microbiome in IBD has been established as findings suggest that in CD and UC, certain phyla, though different in each disease, are affected in count and diversity, with dominance of pathogenic bacteria and loss of protective ones. The commonly used pro‐ and prebiotics are under investigation for their role in the induction and maintenance of remission of IBD, with promising results. Considering the above, the aim of this systematic review is to further investigate the role of probiotics in the maintenance of remission in adult‐onset CD. Materials and Methods: The systematic review was conducted according to the recommendations of the Cochrane Handbook for Systematic Reviews , and the results were reported following the rules of the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA). Eligible studies were identified in the Cochrane database and PubMed; the end of the search date was December 31, 2023. Results: The search identified a total of 2015 items, of which 11 were included in this systematic review. The findings concerning the use of probiotics, either as monotherapy or as adjunctive therapy to traditional treatments, in the maintenance of remission of CD were inconclusive, with four trials indicating a not statistically significant trend favoring their administration for relapse prevention. Conclusions: Although the role of probiotics in CD is doubted, this systematic review highlights the need for further research on the effect of probiotics on the microbiome profiles of IBD patients as well as large‐scale, randomized controlled trials with standardized probiotic formulations, aiming at personalized probiotic therapies with valuable results in CD.

The cornerstone of inflammatory bowel disease (IBD) treatment is immunomodulators. IBD patients are at increased risk of intestinal and extraintestinal malignancy. Ustekinumab is a fully humanized monoclonal anti-IL12/23 antibody with a good safety profile. Malignancies of breast, colon, head and neck, kidney, prostate, thyroid, and non-melanoma skin cancer have been reported among patients who received ustekinumab. We report the case of a 42-year-old Crohn’s patient on long-term treatment with ustekinumab, who developed achromatic malignant melanoma. Crohn’s was diagnosed at the age of 15, with upper and lower gastrointestinal involvement and was initially treated with azathioprine (2mg/kg for 4 years) and infliximab (5mg/kg for 6 weeks). Due to ileal obstruction, the patient underwent stricturoplasty and received adalimumab (40mg every other week) for two years. He then discontinued therapy and a year later underwent right hemicolectomy. Adalimumab was reinstituted (40mg every other week) and the patient remained in clinical remission for two years. His overall exposure to adalimumab was four years. Ustekinumab was initiated due to a relapse and after 3 years, an incident of scalp itching led to the diagnosis metastatic achromatic malignant melanoma bearing BRAF V600E mutation. He received targeted therapy with an initial good response. We aim to point out the risk of dermatologic malignancy in IBD patients on long-term immunosuppression and the lifelong and meticulous evaluation that is required.

Background: The Inflammatory Bowel Disease-Disk (IBD-Disk) is a physician-administered tool that evaluates the functional status of patients with Inflammatory Bowel Disease (IBD). The aim of our study was to validate the content of the IBD-Disk in a Greek cohort of IBD patients. Methods: Two questionnaires [the IBD Disk and the IBD-Disability Index (IBD-DI)] were translated into Greek and administered to IBD patients at baseline visit, after 4 weeks and 6 months. Validation of the IBD Disk included measuring of concurrent validity, reproducibility, and internal consistency. Results: A total of 300 patients were included at baseline and 269 at follow-up. There was a good correlation between the total scores of the IBD-Disk and IBD-DI at baseline (Pearson correlation 0.87, p < 0.001). Reproducibility of the total IBD-Disk score was very good [intra-class correlation coefficient (ICC), 95% confidence interval (CI) 0.89 (0.86–0.91)]. Cronbach’s coefficient alpha for all items achieved 0.90 (95%CI 0.88–0.92), demonstrating a very good homogeneity of the IBD-Disk items. Female gender and extraintestinal manifestations were significantly associated with a higher IBD-Disk total score. Conclusions: The Greek version of the IBD-Disk proved to be a reliable and valid tool in detecting and assessing IBD-related disability in a Greek cohort of IBD patients.

Since inflammatory bowel disease (IBD) patients were excluded from vaccine authorization studies, limited knowledge exists regarding perceptions and unfavorable effects of COVID-19 vaccination in this group. We aimed to investigate the real-world use and adverse events (AEs) of COVID-19 vaccines in Greek IBD patients. Fully vaccinated IBD patients followed in Greek centers were invited to participate. All patients filled out an anonymous online survey concerning the vaccination program, which included information regarding demographics, clinical characteristics, treatment, vaccination perceptions and potential AEs. Overall, 1007 IBD patients were included. Vaccine hesitancy was reported by 49%. Total AEs to vaccination were reported by 81% after dose 1 (D1) and 76% after dose 2 (D2), including isolated injection site reactions (36% and 24% respectively). Systemic AEs were more common after D2 (51%, D2 vs. 44%, D1, p < 0.0001). Very few patients reported new onset abdominal symptoms (abdominal pain 4% (D1), 6% (D2) and diarrhea 5% (D1), 7% (D2)). There were no serious AEs leading to emergency room visit or hospitalization. In multivariate analysis, AEs occurrence was positively associated with young age and female gender (p < 0.0005 for both doses), whereas inactive disease was negatively associated with AE in D1 (p = 0.044). SARS-CoV-2 vaccination in Greek IBD patients demonstrated a favorable and reassuring safety profile.

Background Optimization of treatment with biologics is currently an unmet need for patients with ulcerative colitis (UC). Real-world studies provide neutral estimates of drug efficacy and safety within unselected patient populations and allow for the recognition of specific characteristics that affect response to therapy. Aims We aimed to depict the efficacy of vedolizumab in patients with UC in a real-world setting and identify prognosticators of improved outcomes. Methods Patients with active UC who commenced treatment with vedolizumab were prospectively followed up. Patient-reported outcomes (PROs) and clinical/endoscopic-reported outcomes were recorded at baseline and at weeks 14 and 54. Predefined endpoints of early and persistent efficacy were analyzed against clinical characteristics to identify prognostic factors for response. Results We included 96 patients (anti-TNF-exposed = 38.5%). At week 14, 73 patients (76%) had clinical response and 54 (56.3%) clinical remission. At week 54, the primary endpoint of vedolizumab persistence was met by 72 patients (75%), whereas steroid-free clinical remission by 59.4%. Among patients who had endoscopy, rates for mucosal healing (Mayo endoscopic score of 0) were 29.8% at week 14 and 44.6% at week 54, respectively. Vedolizumab treatment led to significant improvements in quality of life. Corticosteroid-refractory or anti-TNF-refractory disease, articular manifestations, and high baseline UC-PRO2 were associated with decreased efficacy of vedolizumab in the primary and secondary outcomes. Conclusions Vedolizumab is characterized by high efficacy and long-term treatment persistence in UC. More aggressive disease, as indicated by refractoriness to steroids or anti-TNFs and elevated baseline PROs, may predict suboptimal response and help pre-treatment prognostic stratification of patients.