Background: Studies investigating the long-term cellular immune response to SARS-CoV-2 mRNA vaccines in patients with inflammatory bowel disease (IBD) remain limited, particularly among those receiving immunosuppressive therapy. Methods: We prospectively evaluated humoral and cellular immune responses at short-term (4–6 weeks) and long-term (6–12 months) time points following SARS-CoV-2 mRNA vaccination in patients with IBD receiving anti-TNF agents, thiopurines, or combination therapy. We defined the short-term response as the measurement taken 4–6 weeks after the second vaccine dose and the long-term response as the measurement taken between 6 and 12 months after the first determination. A cohort of healthy controls was included for short-term comparative analysis. Results: At long-term follow-up, quantitative humoral responses were reduced in patients receiving anti-TNF monotherapy. In contrast, a reduced quantitative cellular response was found in the thiopurine (median 0.7 UI/mL, p < 0.05) and anti-TNF combo groups (median 0.4 UI/mL, p < 0.01) compared to anti-TNF monotherapy (median 2.2 UI/mL). Conclusions: There was a robust long-term humoral and cellular response to vaccination, but a diminished quantitative cellular response in patients treated with thiopurines or combo therapy compared to anti-TNF monotherapy.

Background: Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy. They can cause immune-mediated colitis (IMC), a potentially severe adverse event. Current data on severe IMC (grade 3–4) are limited, particularly regarding clinical, endoscopic, and histological features. Methods: We conducted a multicenter, retrospective observational study promoted by GETECCU, including adults with solid tumors who developed grade 3–4 IMC requiring hospitalization and systemic therapy. Clinical symptoms, endoscopic findings (Mayo and UCEIS indices), and histological features were systematically collected and analyzed. Results: A total of 196 patients were included. Diarrhea was universal (median 8 bowel movements/day), with 76% reporting abdominal pain and 39% rectal bleeding. Endoscopy (n = 139) revealed vascular pattern loss (80%), mucosal lesions (69%), and Mayo scores ≥2 in 69%. Histopathology (n = 141) showed abnormalities in 85%, including cryptitis (50%), lymphocytic infiltration (48%), and crypt abscesses (37%). Notably, 72% of patients with normal endoscopy had histological inflammation. Endoscopic severity correlated with bleeding and impaired general condition but not with stool frequency or pain intensity. Histological and endoscopic severity were modestly associated. Conclusions: Severe IMC presents with heterogeneous clinical, endoscopic, and histological features, with limited correlation between these domains. Endoscopic findings were often ulcerative and inflammatory, yet histological abnormalities were frequently present even in endoscopically inactive disease. These findings highlight the importance of biopsy in all suspected IMC cases and underscore the need for validated multidimensional assessment tools for accurate diagnosis and management of severe IMC.

Background: Evidence suggests a relationship between ustekinumab (UST) concentrations and therapeutic outcomes in inflammatory bowel disease. Objectives: This study aimed to evaluate the association between UST concentrations during the induction phase and treatment outcomes at week 24 in patients with Crohn’s disease (CD) and ulcerative colitis (UC). The primary outcome was endoscopic remission at week 24, defined as a simple endoscopic score (SES-CD) ⩽2 for CD and a Mayo endoscopic score = 0 for UC. Secondary outcomes included endoscopic response, clinical remission, and treatment persistence. Design: This was a prospective observational study assessing clinical and endoscopic outcomes in CD and UC patients starting UST therapy. Methods: Consecutive patients with CD and UC were included at the initiation of UST treatment. Trough UST concentrations were measured at weeks 8, 16, and 24 after the first intravenous dose, and the main outcomes were assessed at week 24. Endoscopic and clinical parameters were used to evaluate treatment efficacy and persistence. Results: Seventy patients (45 with CD) were enrolled. Those achieving endoscopic remission and response at week 24 had higher UST levels at week 8 (4.5 vs 2.6 μg/mL, p = 0.0028; 4.1 vs 2.4 μg/mL, p = 0.0024, respectively). Patients with UST concentrations in the fourth quartile (Q4) at week 8 (>4.5 μg/mL) had higher rates of endoscopic remission (66.7% (Q4) vs 20% (Q1); 33.3% (Q2); 28.6% (Q3); p = 0.012). A UST concentration threshold of 4.5 μg/mL at week 8 was the best predictor of endoscopic remission (AUC = 0.7, sensitivity 54.5%, specificity 83.8%), while 3.5 μg/mL predicted endoscopic response (AUC = 0.732, sensitivity 53.8%, specificity 87%). Longer disease duration correlated with a higher risk of UST discontinuation (odds ratio, 1.034, 95% confidence interval, 1.002–1.068, p = 0.035). Higher UST concentrations in Q4 did not result in greater drug persistence ( p = 0.319). Conclusion: UST concentrations at week 8 were positively associated with endoscopic outcomes at week 24, with a threshold of 4.5 μg/mL reliably predicting endoscopic remission. Further randomized clinical trials are warranted to explore whether optimizing UST treatment based on post-induction concentrations can enhance therapeutic outcomes.

Background: Irritable bowel syndrome (IBS)-like symptoms are common in patients with ulcerative colitis (UC) in sustained clinical and endoscopic remission and are associated with impaired quality of life. Evidence for targeted treatments in this setting remains limited. Objective: To evaluate the efficacy of the multistrain probiotic VSL#3^® in patients with UC in stable remission and IBS-like symptoms. Methods: In this randomized, double-blind, explorative, placebo-controlled trial, adults with UC in stable remission for ≥6 months and Rome IV C1 or C4 symptoms received VSL#3^® 450 billion colony-forming units or placebo twice daily for 8 weeks. The primary endpoint was symptom relief at week 8 assessed by the 5-point Subject’s Global Assessment of Relief scale. Secondary endpoints included Irritable Bowel Syndrome Symptom Severity Scale scores (IBS-SSS), bowel habits, biochemical remission assessed through fecal calprotectin, IBS-QoL, and IBDQ. Results: Fifty-five patients were randomized. The primary endpoint did not differ significantly between groups. Between-group differences in IBS-SSS total score were not statistically significant at week 8; however, numerically greater and directionally consistent reductions in symptom severity and abdominal pain were observed with VSL#3^® across visits, persisting at follow-up. In exploratory subgroup analyses, restricted to patients with higher abdominal pain and bloating scores at baseline, significant intragroup improvements in abdominal pain and bloating were observed with VSL#3^® but not with placebo. Quality of life improvements were numerically greater and more sustained with VSL#3^®. Conclusions: Within the limitations of the small sample size, these results show a signal of benefit in the quality of life of UC patients with IBS-like symptoms and suggest a potential complementary role for VSL#3^® in symptom-oriented management, particularly for abdominal pain and bloating. Larger, adequately powered randomized trials are warranted to confirm these exploratory findings.