Aim: To evaluate the effectiveness and safety of tofacitinib in ulcerative colitis [UC] in real life.Methods: Patients from the prospectively maintained ENEIDA registry and treated with tofacitinib due to active UC were included. Clinical activity and effectiveness were defined based on Partial Mayo Score [PMS]. Short-term response/remission was assessed at Weeks 4, 8, and 16.Results: A total of 113 patients were included. They were exposed to tofacitinib for a median time of 44 weeks. Response and remission at Week 8 were 60% and 31%, respectively. In multivariate analysis, higher PMS at Week 4 (odds ratio [OR] = 0].2; 95% confidence interval [CI] = 0].1–0.4) was the only variable associated with lower likelihood of achieving remission at Week 8. Higher PMS at Week 4 [OR = 0.5; 95% CI = 0.3–0.7] and higher PMS at Week 8 [OR = 0.2; 95% CI = 0.1–0.5] were associated with lower probability of achieving remission at Week 16. A total of 45 patients [40%] discontinued tofacitinib over time. Higher PMS at Week 8 was the only factor associated with higher tofacitinib discontinuation [hazard ratio = 1.5; 95% CI = 1.3–1.6]. A total of 34 patients had remission at Week 8; of these, 65% had relapsed 52 weeks after achieving remission; the dose was increased to 10 mg/12 h in nine patients, and five of them reached remission again. Seventeen patients had adverse events.Conclusions: Tofacitinib is effective and safe in UC patients in real practice, even in a highly refractory cohort. A relevant proportion of patients discontinue the drug over time, mainly due to primary failure.

Background: One-third of patients with acute severe ulcerative colitis [ASUC] are steroid-refractory. We aimed to review the different options for the management of steroid-refractory ASUC, including not only the standard treatment [cyclosporine and infliximab], but also most recently developed agents [such as vedolizumab, ustekinumab, and tofacitinib].Methods: We performed a bibliographical search to identify studies focusing on the treatment of steroid-refractory ASUC.Results: Cyclosporine and infliximab currently represent the mainstays of salvage therapy and they are generally considered comparable. However, long-term persistence is higher in infliximab therapy, and many clinicians prefer to use infliximab given its ease of use. However, cost of cyclosporine is lower. Sequential rescue therapy after cyclosporine or infliximab failure [with infliximab and cyclosporine, respectively] could be considered in referral centres for highly selected cases. Tofacitinib, due to its rapid effect, represents an attractive rescue option mainly in biologic-experienced patients. The good safety profile of vedolizumab and ustekinumab makes them ideal candidates for use as maintenance therapy in combination with cyclosporine as induction therapy, especially for patients previously exposed to anti-TNFs or thiopurines.Conclusions: Although cyclosporine and infliximab still represent the mainstays of salvage therapy for steroid-refractory ASUC, new therapeutic agents may also play a role. Tofacitinib, due to its rapid effect, is an attractive therapeutic rescue option. Vedolizumab and ustekinumab, as maintenance therapy in combination with the fast-acting cyclosporine as induction therapy, may represent a promising bridging strategy, especially in patients with previous failure to thiopurines and/or anti-TNF agents.

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.

Background: There is limited evidence on the effectiveness of biological therapy in stricturing complications in patients with Crohn’s disease.Aim: The study aims to determine the effectiveness of anti‐tumor necrosis factor (TNF) agents in Crohn’s disease complicated with symptomatic strictures.Methods: In this multicentric and retrospective study, we included adult patients with symptomatic stricturing Crohn’s disease receiving their first anti‐TNF therapy, with no previous history of biological, endoscopic or surgical therapy. The effectiveness of the anti‐TNF agent was defined as a composite outcome combining steroid‐free drug persistence with no use of new biologics or immunomodulators, hospital admission, surgery or endoscopic therapy during follow‐up.Results: Overall, 262 patients with Crohn’s disease were included (53% male; median disease duration, 35 months, 15% active smokers), who received either infliximab (N = 141, 54%) or adalimumab (N = 121, 46%). The treatment was effective in 87% and 73% of patients after 6 and 12 months, respectively, and continued to be effective in 26% after a median follow‐up of 40 months (IQR, 19–85). Nonetheless, 15% and 21% of individuals required surgery after 1 and 2 years, respectively, with an overall surgery rate of 32%. Postoperative complications were identified in 15% of patients, with surgical site infection as the most common. Starting anti‐TNF therapy in the first 18 months after the diagnosis of Crohn’s disease or the identification of stricturing complications was associated with a higher effectiveness (HR 1.62, 95% CI 1.18–2.22; and HR 1.55, 95% CI 1.1–2.23; respectively). Younger age, lower albumin levels, strictures located in the descending colon, concomitant aminosalicylates use or presence of lymphadenopathy were associated with lower effectiveness.Conclusions: Anti‐TNF agents are effective in approximately a quarter of patients with Crohn’s disease and symptomatic intestinal strictures, and 68% of patients are free of surgery after a median of 40 months of follow‐up. Early treatment and some potential predictors of response were associated with treatment success in this setting.

Inflammatory bowel diseases (IBD) belong to the group of immune-mediated diseases (IMIDs). The effect of associated IMIDs in the prognosis in IBD is nowadays unknown. To describe IMIDs associated to IBD patients and evaluate differences linked to the presence or absence of IMIDs. A unicentric retrospective descriptive study was designed. A cohort of 1,448 patients were categorized according to the presence of IMIDs. Clinical characteristics were obtained from IBD database. Univariate and multivariate analysis were performed. 385 patients were diagnosed with associated IMIDs while 1,063 had no associated IMIDs. A prevalence of 26.6% IMIDs associated to IBD was observed. Asthma, skin psoriasis and rheumatoid diseases were most commonly found. Factors associated to the presence of IMIDs were women (OR 1.48; 95 CI 1.17–1.87) and Crohn’s disease (OR 1.35; 95 CI 1.07–1.70). Patients with associated IMIDs required more immunomodulator (OR 1.61; 95 CI 1.27–2.43) and biological treatment (OR 1.81; 95 CI 1.47–2.43). More surgical risk was observed in multivariate analysis in those patients diagnosed with IMIDs prior to the onset of IBD (OR 3.71; 95% CI 2.1–6.56). We considered the presence of IMIDs a poor prognostic factor and suggest a closer monitoring of these patients.

Clinical trials and real-life studies with ustekinumab in Crohn’s disease [CD] have revealed a good efficacy and safety profile. However, these data are scarcely available in elderly patients. Therefore, we aim to assess the effectiveness and safety of ustekinumab in elderly patients with CD. Elderly patients [>60 years old] from the prospectively maintained ENEIDA registry treated with ustekinumab due to CD were included. Every patient was matched with two controls under 60 years of age, according to anti-tumour necrosis factor use and smoking habit. Values for the Harvey–Bradshaw Index [HBI], endoscopic activity, C-reactive protein [CRP] and faecal calprotectin [FC] were recorded at baseline and at weeks 16, 32 and 54. In total, 648 patients were included, 212 of whom were elderly. Effectiveness was similar between young and elderly patients during the follow-up. Steroid-free remission was similar at week 16 [54.6 vs 51.4%, p = 0.20], 32 [53.0% vs 54.5%, p = 0.26] and 54 [57.8% vs 51.1%, p = 0.21]. Persistence of ustekinumab as maintenance therapy was similar in both age groups [log-rank test; p = 0.91]. There was no difference in the rate of adverse effects [14.2% vs 11.2%, p = 0.350], including severe infections [7.1% vs 7.3%, p = 1.00], except for the occurrence of de novo neoplasms, which was higher in older patients [0.7% vs 4.3%, p = 0.003]. Ustekinumab is as effective in elderly patients with CD as it is in non-elderly patients. The safety profile also seems to be similar except for a higher rate of de novo neoplasms, probably related to the age of the elderly patients.