Walter Fries

Background/Objectives: Inflammatory bowel diseases (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), show substantial variability in response to biologic therapies. Ustekinumab, which targets the IL-12/23 pathway, is an established treatment for moderate-to-severe IBD; however, a proportion of patients fail to achieve sustained remission or discontinue treatment over time. This study aimed to evaluate the effectiveness and persistence of ustekinumab and to explore the potential role of pharmacogenetic markers in predicting treatment outcomes. Methods: In this observational cohort study, 98 IBD patients treated with ustekinumab, with or without corticosteroid bridge therapy, in routine clinical practice were enrolled. The primary endpoint was steroid-free remission (SFR) at 12 months, defined as clinical remission without concomitant corticosteroid use, whereas treatment discontinuation was evaluated during follow-up. Genomic DNA was extracted from peripheral blood samples, and four single-nucleotide polymorphisms (SNPs) in selected immune-related genes were analyzed: PTPN2 rs7234029, HLA-C rs10484554, IL23R rs11209026, and IL12B rs6887695. Results: Of the 98 patients included, 73 (74.5%) achieved SFR, whereas 25 (25.5%) did not. Carriers of IL12B rs6887695 variant genotypes showed higher odds of achieving SFR than wild-type patients after adjustment for disease type and baseline disease activity (OR = 4.77; 95% CI, 1.60–14.23; p = 0.005). During follow-up, 16 patients (16.3%) discontinued treatment. Carriers of IL12B rs6887695 variant genotypes also showed a significantly lower hazard of ustekinumab discontinuation than wild-type patients (HR = 0.29; 95% CI, 0.10–0.85; p = 0.024). Conclusions: This study provides real-world evidence supporting the effectiveness and persistence of ustekinumab in IBD patients. IL12B rs6887695 emerged as a potential pharmacogenetic marker associated with favorable ustekinumab outcomes; however, this exploratory and hypothesis-generating finding requires external validation in larger, independent cohorts before clinical application.

Background: Mirikizumab (MIRI), an IgG4 monoclonal antibody targeting IL‐23 p19, was recently licensed for ulcerative colitis (UC). Most available data come from the pivotal trials, but real‐life data are scant. We aimed to evaluate the effectiveness and safety of MIRI in a real‐world setting. Methods: UC patients from 12 centres of the SN‐IBD were prospectively enrolled. The primary endpoints were clinical response, steroid‐free remission (SFR), and reduction of urgency at week 12 and at week 24. As secondary endpoint, the need for prolonged induction was considered. All patients received 3 infusions at monthly intervals of 300 mg MIRI; in case of inadequate response, the induction period was prolonged. Urgency was determined by means of the Urgency Numerical Rating Scale (UNRS). Results: One hundred and five patients were included. Previous failures to 2 or more lines of advanced therapies were present in 74% of patients. At week 12, 24% of patients achieved a clinical response and 53% achieved SFR. At week 24 ( n = 71), the rates were 20% and 68%, respectively. The median urgency score decreased from 6 at baseline to 2 at week 12 and to 1 at week 24 ( p < 0.001, both). Prolonged induction was necessary to half of patients. Adverse events were reported in 5% of patients. Treatment failures occurred in 14 patients (13%). Conclusions: Our real‐life study confirmed the short‐term effectiveness and safety of MIRI in patients with UC especially in relieving bowel urgency. The flexible induction schedule allows an additional gain in response and remission.

Since the prevalence of older patients with ulcerative colitis is increasing, hospitalizations for severe disease in this age group are expected to rise. Older patients are more likely to present with comorbidities and, consequently, frailty, the latter being one of the major drivers of worse outcomes. The conventional sequencing of therapies in acute severe ulcerative colitis-i.e., intravenous steroids followed, in case of refractoriness, by antitumor necrosis factor (TNF) agents, ciclosporin A, or Janus kinase inhibitors such as tofacitinib or upadacitinib-may frequently be contraindicated in older patients or may carry an increased risk of severe adverse events beyond infections. In the absence of specific guidelines, the implementation of and strict adherence to a structured, time-bound decision tree is essential in order to avoid unnecessarily prolonged treatment with systemic steroids in frail patients, which may lead to deleterious outcomes, particularly in those requiring surgery. Recent reports on adjunctive measures, such as hyperbaric oxygen therapy or total enteral nutrition, may also be considered given their encouraging safety profile.

Objectives: Anti-TNF-α therapies have transformed the management of Inflammatory Bowel Disease (IBD), yet a substantial proportion of patients fail to respond, highlighting the urgent need for predictive biomarkers. Mucosal TNF-α mRNA quantification in fresh biopsies has shown promise but showed several problems for routine clinical use. This study aimed to validate a clinically feasible method for TNF-α quantification in formalin-fixed paraffin-embedded (FFPE) tissues and to assess its correlation with established measures of disease activity. Methods: FFPE and matched fresh-frozen biopsies from 54 ulcerative colitis patients were analyzed. Total RNA was extracted from FFPE sections, and TNF-α RNA was quantified by RT-qPCR and compared with fresh tissue expression levels. Molecular data were correlated with clinical (pMayo), endoscopic (Mayo Endoscopic Score, MES), and histological (Geboes) indices. Results: TNF-α expression in FFPE samples strongly correlated with fresh tissue levels (r = 0.83, p < 0.0001). High TNF-α expression in FFPE tissue was significantly associated with active endoscopic mucosal disease (MES ≥ 1; OR 28, 95% CI 3.31–237; p < 0.0001) and with histological inflammation (Geboes ≥ 3.1; OR 0.12, 95% CI 0.02–0.59; p = 0.009). Fresh tissue TNF-α levels showed similar associations. Clinical parameters such as age, sex, and pMayo score did not significantly correlate with mucosal TNF-α expression. RT-qPCR quantification of TNF-α in FFPE tissue is a reliable, cost-effective surrogate for fresh biopsy analysis and correlates strongly with endoscopic and histological disease activity. Conclusions: This method offers a practical approach for integrating molecular biomarkers into routine pathology workflows, supporting the implementation of personalized treatment strategies in IBD.

Background & aims: The optimal management of inflammatory bowel disease (IBD) patients with a partial response after intravenous (IV) vedolizumab (VDZ) induction remains unclear. Methods: PRIVEDO was an observational, non-randomized, open-label, prospective cohort study conducted within the Sicilian Network for IBD. It compared subcutaneous (SC) VDZ (108 mg every 2 weeks) versus intensified IV VDZ (300 mg every 4 weeks) in Crohn’s disease (CD) or ulcerative colitis (UC) patients with a partial response at Week 14 post-induction. Partial response was defined as: (1) clinical remission with fecal calprotectin >250 µg/g and/or steroid use, or (2) a reduction in the Harvey-Bradshaw Index by ≥3 points (for CD) or in the Partial Mayo Score by ≥2 points (for UC) from baseline, without fulfilling clinical remission criteria. The primary endpoint was steroid-free clinical remission with fecal calprotectin <250 µg/g at Weeks 26 and 52. The secondary endpoints were clinical benefit (remission or partial response), regardless of calprotectin values, and treatment persistence. Results: 107 patients were enrolled (CD: 58/107, 54.2%; UC: 49/107, 45.8%), allocated to SC (n = 52) or IV (n = 55) groups. The primary endpoint was met more often with SC VDZ at Week 26 (30/52, 57.7% vs. 14/55, 25.5%; P < 0.001; odds ratio [OR]: 3.57, P = 0.004 at multivariable analysis) and at Week 52 (25/52, 48.1% vs. 14/55, 25.5%; P = 0.016; OR: 3.05, P = .029 at multivariable analysis). Clinical benefit was also higher in the SC group at both timepoints, though not statistically significant. Treatment persistence was comparable between the 2 groups (log-rank test, P = .225). Conclusions: In IBD patients with partial response to IV VDZ induction, switching to SC VDZ may lead to more profound remission than continuing IV optimization.

Introduction: The risk of new or recurrent cancer in inflammatory bowel disease (IBD) patients with a history of cancer treated with immunomodulators (IMMs), including conventional immunosuppressors (ISSs), biologics or small molecules is undefined. The primary aim was to assess the frequency of new or recurrent cancer in IBD patients treated with IMMs after first cancer. The secondary aim was to evaluate risk factors for new/recurrent cancer in the same IBD population. Methods: In a retrospective multicenter study, all IBD patients using any IMM after first (index) cancer were enrolled. Inclusion criteria: Crohn’s disease (CD) or ulcerative colitis (UC), history of any cancer, detailed clinical history, and follow-up after cancer of ≥6 months. Exclusion criteria: IMM use for ≤3 months. Results: In total, 122 IBD patients (84 CD, 38 UC) treated with IMMs after first cancer were enrolled (age 59.5 [26–89] years). Index cancer included (n = [%]) genitourinary tract cancer (18 [14.8]), non-melanotic skin cancer (NMSC) (17 [13.9]), breast cancer (15 [12.3]), thyroid cancer (13 [10.7]), melanoma (14 [11.4]), colorectal cancer (CRC) (11 [9.0]), hematopoietic cancer (9 [7.4]), prostatic cancer (8 [6.6]), neuroendocrine cancer (4 [3.3]), head and neck cancer (3 [2.5]), liver cancer (3 [2.5]), endometrium cancer (2 [1.6]), lung cancer (1 [0.8]) and others (3 [2.5]). ISSs after cancer included (n = [%]) thiopurines (10 [37]), methotrexate (MTX) (14 [51.9]) and others (3 [11.1]) Biologics included (n = [%]) TNF-inhibitors (36 [32.4]), vedolizumab (60 [53.6]), ustekinumab (45 [40.2]), small molecules (9 [7.3]) and others (6 [5.4]). In a median follow-up of 8 [1–45] years after index cancer, 12/122 (9.8%) patients using IMMs after cancer developed new or recurrent cancer. No risk factors for new/recurrent cancer (i.e., age at diagnosis of cancer, smoke, gender, IBD type, IMM use, duration before or after cancer) were identified. Conclusions: In a multicenter study, ISSs or biologics after cancer were not identified as risk factors for new or recurrent cancer in IBD. However, IMMs were used after a long-term interval from index cancer.

Background: Patients with ulcerative colitis (UC) and Crohn’s disease (CD) have an increased cardiovascular risk (CVR). The aim of the present study was to stratify the CVR of patients with UC and CD according to the most recent guidelines via carotid ultrasound (US) to detect subclinical atherosclerotic disease. Methods: Demographic and disease-related data of consecutive patients with IBD were prospectively collected along with information on blood pressure, body mass index, lipid profile, and concomitant medications. CVR was stratified at inclusion according to the most recent version of Systematic Coronary Risk Evaluation 2 (SCORE2) and re-stratified after carotid US when subclinical atherosclerotic disease was detected. Results: A total of 166 patients aged ≥ 40 years with IBD were included. Before carotid US evaluation, 43.4% of patients with IBD were at moderate risk, 40.3% at high risk, and 16.3% at very high risk. With carotid US, subclinical atherosclerosis was diagnosed in 48% of patients, leading to CVR re-stratification from moderate to high in 18% of patients and from high to very high in 4% of patients. The only predictive factor for re-stratification was failure with more than two biologics (p = 0.047; OR 2.187, 95% CI: 1.004–4.741). Conclusions: CVR is considerably prevalent in patients with IBD. Carotid US may help to re-classify CVR and should be considered as a risk modifier in patients at intermediate risk. Screening for CVD risk factors should be recommended in IBD.

Background/Objectives: Patients with inflammatory bowel disease (IBD) are at increased risk of severe infections, particularly when undergoing immunosuppressive therapy. Vaccination is a key preventive strategy, but coverage in this group is often suboptimal. This study evaluated vaccination coverage among IBD patients at diagnosis/referral and after admission to a structured hospital-based vaccination pathway. Methods: We conducted an observational study (February 2022–February 2025) at the Vaccination Center (VC) of the University Hospital “G. Martino” in Messina, Italy. Adult IBD patients referred by gastroenterologists were assessed for vaccination status using hospital and regional registries, and personalized schedules were developed based on Italian National Vaccine Prevention Plan guidelines. Descriptive statistics were applied to assess baseline and post-intervention vaccination coverage. Results: Of 154 participants (mean age 64 years; 51.9% male), 55.4% were on immunosuppressive therapy. Baseline coverage was heterogeneous: influenza, 6.5%; PCV13, 25.5%; PPV23, 26.6%; herpes zoster, 62.3%; and COVID-19 primary cycle, 79.6%. After enrollment, substantial improvements were observed: influenza, 89.2%; PCV13, 74.5%; PPV23, 67.0%; herpes zoster, 75.4%; and COVID-19 primary cycle, 96.8%. Coverage for catch-up vaccines also improved (e.g., HBV went from 1.9% to 44.2%). However, uptake of COVID-19 booster doses during the study period remained low (15.6%). No significant differences emerged by sex or treatment subgroup. Conclusions: A structured, collaborative care pathway between gastroenterologists and public health specialists significantly improved vaccination coverage among IBD patients. Despite gains, gaps persist in COVID-19 booster uptake and catch-up vaccinations. Integration of vaccination services into routine IBD management is essential to enhance protection in this high-risk population.