Background and Aims Ustekinumab is approved for the treatment of Crohn’s disease [CD]. Systematically registered prospective real-world data are scarce. We therefore aimed to study the effectiveness, safety and usage of ustekinumab for CD in everyday practice. Methods We prospectively enrolled CD patients initiating ustekinumab in regular care between December 2016 and January 2019. Clinical (Harvey Bradshaw Index [HBI]), biochemical (C-reactive protein [CRP] and faecal calprotectin [FCP]), extra-intestinal manifestations and, peri-anal fistula activity, ustekinumab dosage, concomitant medication use, and adverse events were documented at weeks 0, 12, 24, and 52. The primary outcome was corticosteroid-free clinical remission. Results In total, 221 CD patients were included (98.6% anti-tumour necrosis factor [TNF] and 46.6% vedolizumab exposed) with a median follow-up of 52.0 weeks [interquartile range 49.3–58.4]. Corticosteroid-free clinical remission rates at weeks 24 and 52 were 38.2% and 37.1%, respectively. An initial dosing schedule of 8 weeks, compared to 12 weeks, correlated with a lower discontinuation rate [20.0% vs 42.6%, p = 0.01], but comparable corticosteroid-free clinical remission at week 52 (46.3% [q8w] vs 34.6% [q12w], p = 0.20). There was no clinical benefit of combination therapy after 52 weeks when compared to ustekinumab monotherapy [combi 40.6% vs mono 36.0%, p = 0.64]. At baseline, 28 patients had active peri-anal fistula, of whom 35.7% showed complete clinical resolution after 24 weeks. During follow-up we encountered six severe infections [3.5 per 100 patient-years], with all patients being on concomitant immunosuppressant therapies. Ustekinumab treatment discontinuation was observed in 75 [33.9%] patients mainly due to lack of response. Conclusion Ustekinumab is a relatively safe and effective treatment option for CD patients with prior failure of anti-TNF and anti-integrin therapies.

Summary Background Both vedolizumab and ustekinumab can be considered for the treatment of Crohn’s disease (CD) when anti‐TNF treatment fails. However, head‐to‐head trials are currently not available or planned. Aim To compare vedolizumab and ustekinumab in Crohn´s disease patients in a prospective registry specifically developed for comparative studies with correction for confounders. Methods Crohn´s disease patients, who failed anti‐TNF treatment and started vedolizumab or ustekinumab in standard care as second‐line biological, were identified in the observational prospective Dutch Initiative on Crohn and Colitis Registry. Corticosteroid‐free clinical remission (Harvey Bradshaw Index ≤4), biochemical remission (C‐reactive protein ≤5 mg/L and fecal calprotectin ≤250 µg/g), combined corticosteroid‐free clinical and biochemical remission, and safety outcomes were compared after 52 weeks of treatment. To adjust for confounding and selection bias, we used multiple logistic regression and propensity score matching. Results In total, 128 vedolizumab‐ and 85 ustekinumab‐treated patients fulfilled the inclusion criteria. After adjusting for confounders, ustekinumab‐treated patients were more likely to achieve corticosteroid‐free clinical remission (odds ratio [OR]: 2.58, 95% CI: 1.36‐4.90, P = 0.004), biochemical remission (OR: 2.34, 95% CI: 1.10‐4.96, P = 0.027), and combined corticosteroid‐free clinical and biochemical remission (OR: 2.74, 95% CI: 1.23‐6.09, P = 0.014), while safety outcomes (infections: OR: 1.26, 95% CI: 0.63‐2.54, P = 0.517; adverse events: OR: 1.33, 95% CI: 0.62‐2.81, P = 0.464; hospitalisations: OR: 0.67, 95% CI: 0.32‐1.39, P = 0.282) were comparable between the two groups. The propensity score matched cohort with sensitivity analyses showed comparable results. Conclusions Ustekinumab was associated with superior effectiveness outcomes when compared to vedolizumab, while safety outcomes were comparable after 52 weeks of treatment in CD patients who have failed anti‐TNF treatment.

Background: Tofacitinib is a Janus kinase inhibitor approved for the treatment of ulcerative colitis (UC).Aim: To evaluate effectiveness, safety and use of tofacitinib in daily practice.Methods: UC patients initiating tofacitinib were prospectively enrolled in 15 hospitals in the Netherlands. Corticosteroid-free clinical remission (short clinical colitis activity index [SCCAI] ≤2), biochemical remission (faecal calprotectin level ≤250 µg/g), combined corticosteroid-free clinical and biochemical remission, predictors of remission, safety outcomes, treatment dose and effect on lipids were determined at weeks 12 and 24. Endoscopic outcomes were evaluated in centres with routine endoscopic evaluation.Results: In total, 123 UC patients (95% anti-TNF, 62% vedolizumab and 3% ustekinumab experienced) were followed for a median duration of 24 weeks (interquartile range 12-26). The proportion of patients in corticosteroid-free clinical, biochemical, and combined corticosteroid-free clinical and biochemical remission rate at week 24 was 29% (n: 22/77), 25% (n: 14/57), and 19% (n: 11/57) respectively. Endoscopic remission (Mayo = 0) was achieved in 21% of patients at week 12 (n: 7/33). Prior vedolizumab exposure was associated with reduced clinical remission (odds ratio 0.33, 95% confidence interval [CI] 0.11-0.94). At week 24, 33% (n: 14/42) of patients still on tofacitinib treatment used 10 mg twice daily. In total, 33 tofacitinib-related adverse events (89 per 100 patient years) occurred, 7 (6% of total cohort) resulted in | 881 BIEMANS Et Al. How to cite this article: Biemans VBC, Sleutjes JAM, de Vries AC, et al; on behalf of the Dutch Initiative on Crohn and Colitis (ICC). Tofacitinib for ulcerative colitis: results of the prospective Dutch Initiative on Crohn and Colitis (ICC) registry. Aliment Pharmacol Ther. 2020;51:880-888. https://doi.

Background and aims The COVID-19 risk and disease course in inflammatory bowel disease (IBD) patients remains uncertain. Therefore, we aimed to assess the clinical presentation, disease course and outcomes of COVID-19 in IBD patients. Second, we determined COVID-19 incidences in IBD patients and compared this with the general population. Methods We conducted a multicenter, nationwide IBD cohort study in the Netherlands and identified patients with COVID-19. First, we assessed the COVID-19 disease course and outcomes. Second, we compared COVID-19 incidences between our IBD study cohort and the general Dutch population. Results We established an IBD cohort of 34,763 patients. COVID-19 was diagnosed in 100/34,763 patients (0.29%). 20/100 patients (20%) had severe COVID-19 defined as admission to the intensive care unit, mechanical ventilation, and/or death. Hospitalization occurred in 59/100 (59.0%) patients and 13/100 (13.0%) died. All patients who deceased had comorbidities and all but one were > 65 years. In line, we identified > 1 comorbidity as an independent risk factor for hospitalization (OR 4.20, 95% CI 1.58-11.17, p = 0.004). Incidences of COVID-19 between the IBD study cohort and the general population were comparable (287.6 (95% CI 236.6-349.7) versus 333.0 (95% CI 329.3-336.7) per 100,000 patients, respectively; p = 0.15). Conclusions Of 100 cases with IBD and COVID-19, 20% developed severe COVID-19, 59% was hospitalized and 13% died. A comparable COVID-19 risk was found between the IBD cohort (100/34,763 = 0.29%) and the general Dutch population. The presence of > 1 comorbidities was an independent risk factor for hospitalization due to COVID-19.

Although placement of SEMS (uncovered or partially covered) for palliation of extrahepatic bile duct obstruction initially is more expensive than placement of plastic stents, SEMS have longer functional time. The total costs after 1 year do not differ significantly with stent type. Dutch Clinical Trial Registration no: NTR1361.