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Background and Aims The development programm UNIFI has shown promising results of ustekinumab in ulcerative colitis [UC] treatment which should be confirmed in clinical practice. We aimed to evaluate the durability, effectiveness, and safety of ustekinumab in UC in real life. Methods Patients included in the prospectively maintained ENEIDA registry, who received at least one intravenous dose of ustekinumab due to active UC [Partial Mayo Score [PMS]>2], were included. Clinical activity and effectiveness were defined based on PMS. Short-term response was assessed at Week 16. Results A total of 95 patients were included. At Week 16, 53% of patients had response [including 35% of patients in remission]. In the multivariate analysis, elevated serum C-reactive protein was the only variable significantly associated with lower likelihood of achieving remission. Remission was achieved in 39% and 33% of patients at Weeks 24 and 52, respectively; 36% of patients discontinued the treatment with ustekinumab during a median follow-up of 31 weeks. The probability of maintaining ustekinumab treatment was 87% at Week 16, 63% at Week 56, and 59% at Week 72; primary failure was the main reason for ustekinumab discontinuation. No variable was associated with risk of discontinuation. Three patients reported adverse events; one of them had a fatal severe SARS-CoV-2 infection. Conclusions Ustekinumab is effective in both the short and the long term in real life, even in a highly refractory cohort. Higher inflammatory burden at baseline correlated with lower probability of achieving remission. Safety was consistent with the known profile of ustekinumab.

Background Three anti-TNFs (one intravenous and two subcutaneous) are licensed for the treatment of ulcerative colitis (UC). However, it is not known if the efficacy of a second anti-TNF changes on whether it is intravenous or subcutaneous; this could justify the indication of biological agents with a different mechanism of action in second line. The aim of this study was to compare the efficacy of a second subcutaneous or intravenous anti-TNF in UC. Methods Patients from the prospectively maintained ENEIDA registry treated with consecutively intravenous and subcutaneous anti-TNF, who were naïve to biological agents, were identified. Patients were classified according to the administration route of the first anti-TNF in: IVi (intravenous initially) or SCi (subcutaneous initially). Patients treated for extraintestinal manifestations or pouchitis were excluded. Clinical activity and effectiveness were defined based on Partial Mayo Score (PMS) at baseline, 14 and 52 weeks. Loss of response, dose-escalation and treatment discontinuation were also assessed. Results 372 UC patients were included (270 IVi and 102 SCi). Both cohorts were similar in clinical-epidemiological characteristics, except for a higher proportion of patients with moderate-to-severe clinical activity at the beginning of the first anti-TNF in the IVi group (82% vs. 71%; p = 0.017) and at the beginning of the second anti-TNF (62% vs. 74%; p = 0.04). Clinical response and remission rates at week 14 for the second anti-TNF were 41% and 29% in IVi vs. 47% and 25% in SCi, respectively (p = ns). At week 52, clinical response/remission rates of the second anti-TNF were 37%/32% in IVi vs. 40%/29% in SCi (p = ns). A higher response rate at 14 weeks with the second anti-TNF was detected in the SCi group (40% vs. 68%; p = 0.012) when the reason for withdrawal of the first anti-TNF was secondary loss of response. The cumulative persistence of the second anti-TNF treatment in IVi and SCi were 55% and 54% after 1 year, and 41% and 40% after 2 years, respectively (p = ns). The SCi group had lower rates of dose-escalation with the second anti-TNF than IVi (34% and 29% in SCi vs. 57% and 49% in EVi, at 12 and 24 months, respectively -p = 0.004-). Dose-escalation of the first anti-TNF and moderate-to-severe clinical activity at the beginning of the second anti-TNF were associated with a lower probability of remission with the second anti-TNF in the short- and long-term. Conclusion The efficacy of infliximab after failure/intolerance of a subcutaneous anti-TNF is similar to that of subcutaneous anti-TNFs after infliximab failure/intolerance.

Background Patients with gastrointestinal bleeding during anticoagulant and/or antiplatelet therapy represent a clinical challenge. Aim To determine the risk/rates of rebleeding, vascular events and death in patients treated with antiplatelet or anticoagulant agents who developed major gastrointestinal bleeding METHODS: This was an observational cohort study of patients who developed gastrointestinal bleeding while on antiplatelet and/or anticoagulant therapy. Drug use information was collected prospectively during bleeding events. Cox proportional hazards models were used to evaluate rebleeding, vascular events and death. Results Among 871 patients (mean age 78.9 ± 8.6 years), 38.9% used an anticoagulant, 52.5% used an antiplatelet and 8.6% used both; 93.1% interrupted treatment after gastrointestinal bleeding and 80.5% restarted therapy within 7.6 ± 36.4 days; 38.7% had upper gastrointestinal bleeds, 46.7% lower gastrointestinal bleeds and 14.6% gastrointestinal bleeds of unknown origin. Median follow-up was 24.9 months (IQR: 7.0-38.0). Resumption of both therapies was associated with a higher risk of rebleeding, lower risk of ischaemic events or death and a similar risk for upper and lower gastrointestinal events. Resumption of therapy ≤ 7 days after bleeding showed a similar pattern with no differences in death. Rebleeding rates were higher in anticoagulant vs antiplatelet patients (138.0 vs 99.0 events per 1000 patient-years), and the bleeding location was identical in 61.8% of cases. Conclusions Resumption of anticoagulant or antiplatelet therapy after a gastrointestinal bleeding event was associated with a lower risk of vascular events and death and a higher rebleeding risk. The benefits of early reinstitution of anticoagulant/antiplatelet therapy outweigh the gastrointestinal-related risks.

Background and Aims Primary sclerosing cholangitis [PSC] is usually associated with inflammatory bowel disease [IBD]. An increased risk of malignancies, mainly colorectal cancer [CRC] and cholangiocarcinoma [CCA], has been reported in PSC-IBD patients. Our aim was to determine the clinical characteristics and management of PSC in IBD patients, and the factors associated with malignancies. Methods PSC-IBD patients were identified from the Spanish ENEIDA registry of GETECCU. Additional data were collected using the AEG-REDCap electronic data capture tool. Results In total, 277 PSC-IBD patients were included, with an incidence rate of 61 PSC cases per 100 000 IBD patient-years, 69.7% men, 67.5% ulcerative colitis and mean age at PSC diagnosis of 40 ± 16 years. Most patients [85.2%] were treated with ursodeoxycholic acid. Liver transplantation was required in 35 patients [12.6%] after 79 months (interquartile range [IQR] 50–139). It was more common in intra- and extrahepatic PSC compared with small-duct PSC (16.3% vs 3.3%; odds ratio [OR] 5.7: 95% confidence interval [CI] = 1.7–19.3). The incidence rate of CRC since PSC diagnosis was 3.3 cases per 1000 patient-years [95% CI = 1.9–5.6]. Having symptoms of PSC at PSC diagnosis was the only factor related to an increased risk of CRC after IBD diagnosis [hazard ratio= 3.3: 95% CI = 1.1–9.9]. CCA was detected in seven patients [2.5%] with intra- and extrahepatic PSC, with median age of 42 years [IQR 39–53], and presented a lower life expectancy compared with patients without CCA and patients with or without CRC. Conclusions PSC-IBD patients with symptoms of PSC at PSC diagnosis have an increased risk of CRC. CCA was only diagnosed in patients with intra- and extrahepatic PSC and was associated with poor survival.