Comparative Study of the Effectiveness of Vedolizumab Versus Ustekinumab After Anti-TNF Failure in Crohn's Disease (Versus-CD): Data from the ENEIDA Registry.

BACKGROUND: Both vedolizumab and ustekinumab are approved for the management of Crohn's disease [CD]. Data on which one would be the most beneficial option when anti-tumour necrosis factor [anti-TNF] agents fail are limited. AIMS: To compare the durability, effectiveness, and safety of vedolizumab and ustekinumab after anti-TNF failure or intolerance in CD. METHODS: CD patients from the ENEIDA registry who received vedolizumab or ustekinumab after anti-TNF failure or intolerance were included. Durability and effectiveness were evaluated in both the short and the long term. Effectiveness was defined according to the Harvey-Bradshaw index [HBI]. The safety profile was compared between the two treatments. The propensity score was calculated by the inverse probability weighting method to balance confounder factors. RESULTS: A total of 835 patients from 30 centres were included, 207 treated with vedolizumab and 628 with ustekinumab. Dose intensification was performed in 295 patients. Vedolizumab [vs ustekinumab] was associated with a higher risk of treatment discontinuation (hazard ratio [HR] 2.55, 95% confidence interval [CI]: 2.02-3.21), adjusted by corticosteroids at baseline [HR 1.27; 95% CI: 1.00-1.62], moderate-severe activity in HBI [HR 1.79; 95% CI: 1.20-2.48], and high levels of C-reactive protein at baseline [HR 1.06; 95% CI: 1.02-1.10]. The inverse probability weighting method confirmed these results. Clinical response, remission, and corticosteroid-free clinical remission were higher with ustekinumab than with vedolizumab. Both drugs had a low risk of adverse events with no differences between them. CONCLUSION: In CD patients who have failed anti-TNF agents, ustekinumab seems to be superior to vedolizumab in terms of durability and effectiveness in clinical practice. The safety profile is good and similar for both treatments.

Clinical and treatment outcomes of a second subcutaneous or intravenous anti-TNF in patients with ulcerative colitis treated with two consecutive anti-TNF agents: data from the ENEIDA registry.

Background: Infliximab seems to be the most efficacious of the three available anti-TNF agents for ulcerative colitis (UC) but little is known when it is used as the second anti-TNF. Objectives: To compare the clinical and treatment outcomes of a second subcutaneous or intravenous anti-TNF in UC patients. Design: Retrospective observational study. Methods: Patients from the ENEIDA registry treated consecutively with infliximab and a subcutaneous anti-TNF (or vice versa), naïve to other biological agents, were identified and grouped according to the administration route of the first anti-TNF into IVi (intravenous initially) or SCi (subcutaneous initially). Results: Overall, 473 UC patients were included (330 IVi and 143 SCi). Clinical response at week 14 was 42.7% and 48.3% in the IVi and SCi groups (non-statistically significant), respectively. Clinical remission rates at week 52 were 32.8% and 31.4% in the IVi and SCi groups (nonsignificant differences), respectively. A propensity-matched score analysis showed a higher clinical response rate at week 14 in the SCi group and higher treatment persistence in the IVi group. Regarding long-term outcomes, dose escalation and discontinuation due to the primary failure of the first anti-TNF and more severe disease activity at the beginning of the second anti-TNF were inversely associated with clinical remission. Conclusion: The use of a second anti-TNF for UC seems to be reasonable in terms of efficacy, although it is particularly reduced in the case of the primary failure of the first anti-TNF. Whether the second anti-TNF is infliximab or subcutaneous does not seem to affect efficacy.

OBJECTIVES: To compare the clinical and treatment outcomes of a second subcutaneous or intravenous anti-TNF in UC patients. DESIGN: Retrospective observational study. METHODS: Patients from the ENEIDA registry treated consecutively with infliximab and a subcutaneous anti-TNF (or vice versa), naïve to other biological agents, were identified and grouped according to the administration route of the first anti-TNF into IVi (intravenous initially) or SCi (subcutaneous initially). RESULTS: Overall, 473 UC patients were included (330 IVi, 143 SCi). Clinical response at week 14 was 42.7% and 48.3% in the IVi and SCi groups (non-statistically significant), respectively. Clinical remission rates at week 52 were 32.8% and 31.4%, in the IVi and SCi groups (nonsignificant differences), respectively. A propensity-matched score analysis showed a higher clinical response rate at week 14 in the SCi group and higher treatment persistence in the IVi group. Regarding long-term outcomes, dose escalation and discontinuation due to the primary failure of the first anti-TNF and more severe disease activity at the beginning of the second anti-TNF were inversely associated with clinical remission. CONCLUSION: The use of a second anti-TNF for UC seems to be reasonable in terms of efficacy, although it is particularly reduced in the case of the primary failure of the first anti-TNF. Whether the second anti-TNF is infliximab or subcutaneous does not seem to affect efficacy.

Clinical and treatment outcomes of a second subcutaneous or intravenous anti-TNF in patients with ulcerative colitis treated with two consecutive anti-TNF agents. Data from the ENEIDA registry Background: Infliximab seems to be the most efficacious of the three available anti-TNF agents for ulcerative colitis (UC), but little is known when it is used as the second anti-TNF.

Risk of rebleeding, vascular events and death after gastrointestinal bleeding in anticoagulant and/or antiplatelet users.

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.

Clinical Characteristics, Associated Malignancies and Management of Primary Sclerosing Cholangitis in Inflammatory Bowel Disease Patients: A Multicentre Retrospective Cohort Study.

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.

Short and long-term effectiveness and safety of vedolizumab in inflammatory bowel disease: results from the ENEIDA registry.

BACKGROUND: Effectiveness of vedolizumab in real world clinical practice is unknown. AIM: To evaluate the short and long-term effectiveness of vedolizumab in patients with inflammatory bowel disease (IBD). METHODS: Patients who received at least 1 induction dose of vedolizumab were included. Effectiveness was defined based on Harvey-Bradshaw index (HBI) in Crohn's disease (CD) and Partial Mayo Score (PMS) in ulcerative colitis (UC). Short-term response was assessed at week 14. Variables associated with short-term remission were identified by logistic regression analysis. The Kaplan-Meier method was used to evaluate the long-term durability of vedolizumab treatment. Cox model was used to identify factors associated with discontinuation of treatment and loss of response. RESULTS: 521 patients were included (median follow-up 10 months [interquartile range 5-18 months]). At week 14, 46.8% had remission and 15.7% clinical response. CD (vs UC), previous surgery, higher CRP concentration and disease severity at baseline were significantly associated with impaired response. The rate of vedolizumab discontinuation was 37% per patient-year of follow-up (27.6% in UC and 45.3% in CD, P < 0.01). CD (vs UC), anaemia at baseline, steroids during induction and CRP concentration were associated with lower durability of treatment. Seven per cent of patients developed adverse events, infections being the most frequent. CONCLUSIONS: Over 60% of IBD patients respond to vedolizumab. Many patients discontinue treatment over time. CD and disease burden impair both short- and long-term response. Vedolizumab seems to be safe in clinical practice.