Background Post-marketing data are required to confirm the durability and the long-term benefit and safety of UST in CD in clinical practice. Our aims were: (1) to evaluate the retention rate of UST in CD patients and to identify predictive factors of UST discontinuation; (2) to assess UST short-term effectiveness; (3) to analyse the durability of the response to UST in the long-term; and (4) to evaluate the safety of UST in clinical practice. Methods Retrospective, multicentre study (>60 centres). Patients with active CD [(Harvey–Bradshaw (HBI) >4)] that received at least one dose of UST intravenously before July 2018 were included. Clinical activity plus biochemical parameters were assessed at every UST administration. Clinical remission was defined as HBI score ≤4, and clinical response as a decrease in HBI ≥3 points. Loss of efficacy was defined as reappearance of symptoms that led to intensify the treatment dose, add another medication to control CD, switching or surgery in patients with short-term remission. The retention rate of UST treatment and the cumulative incidence of loss of efficacy were evaluated by survival curves, and predictive factors were assessed by Cox-regression. The short-term response was evaluated at week 8 and after the induction (week 16). Factors associated with short-term remission were assessed by multivariate analysis. Adverse events were recorded. Data quality was assured by remote monitoring. Results 331 CD patients have been included up to date (Table 1). The incidence rate of UST discontinuation was 15% per patient-year of follow-up: 8%, 13% and 20% at 6, 12 and 18 months (Figure 1). Previous surgery was the only factor associated with a higher risk of UST discontinuation [Hazard ratio (HR) = 2.03, 95% confidence interval (CI) = 1.1–3.6]. Short-term efficacy is shown in Figure 2. Previous surgery (OR = 0.3, 95% CI = 0.2–0.6) and higher HBI score at baseline (OR = 0.8, 95% CI=0.8–0.9) were associated with an impaired response to UST at week 16. The cumulative incidence of loss of response was 32% per-patient-year of follow-up (Figure 3); A higher HBI score at baseline was associated with a higher risk of losing response (HR = 1.2, 95% CI = 1.1–1.3). Neither the concomitant treatment with immunosuppressants nor the number of previous biologics were associated with UST short- and long-term benefit. Thirty adverse events were reported in 25 (7%) patients (Table 2). Conclusion Sustain is the largest real clinical practice study of UST to treat CD patients with the longest follow-up reported to date. UST was demonstrated to be effective in real-world use in the short and long run. Safety was consistent with the known profile of UST.

Background Large real-world-evidence studies are required to confirm the durability of response, effectiveness, and safety of ustekinumab in Crohn’s disease (CD) patients in real-world clinical practice. Methods A retrospective, multicentre study was conducted in Spain in patients with active CD who had received ≥1 intravenous dose of ustekinumab for ≥6 months. Primary outcome was ustekinumab retention rate; secondary outcomes were to identify predictive factors for drug retention, short-term remission (week 16), loss of response and predictive factors for short-term efficacy and loss of response, and ustekinumab safety. Results A total of 463 patients were included. Mean baseline Harvey-Bradshaw Index was 8.4. A total of 447 (96.5%) patients had received prior biologic therapy, 141 (30.5%) of whom had received ≥3 agents. In addition, 35.2% received concomitant immunosuppressants, and 47.1% had ≥1 abdominal surgery. At week 16, 56% had remission, 70% had response, and 26.1% required dose escalation or intensification; of these, 24.8% did not subsequently reduce dose. After a median follow-up of 15 months, 356 (77%) patients continued treatment. The incidence rate of ustekinumab discontinuation was 18% per patient-year of follow-up. Previous intestinal surgery and concomitant steroid treatment were associated with higher risk of ustekinumab discontinuation, while a maintenance schedule every 12 weeks had a lower risk; neither concomitant immunosuppressants nor the number of previous biologics were associated with ustekinumab discontinuation risk. Fifty adverse events were reported in 39 (8.4%) patients; 4 of them were severe (2 infections, 1 malignancy, and 1 fever). Conclusions Ustekinumab is effective and safe as short- and long-term treatment in a refractory cohort of CD patients in real-world clinical practice.

(1) Background: Evidence on the outcomes of ustekinumab treatment in real-world Crohn’s disease (CD) patients is needed. Our aim was to evaluate the effectiveness and safety of ustekinumab in CD, reported by observational studies. (2) Methods: bibliographical searches were performed (PubMed, EMBASE). Selection: observational studies assessing the effectiveness and safety of ustekinumab in CD. Exclusion criteria: studies using ustekinumab as a prophylaxis for postoperative recurrence or perianal disease. Data synthesis: effectiveness by intention-to-treat (random-effects model). Data were stratified by study design, population included, administered dose, and prior biologic exposure. (3) Results: A total of 63 studies (8529 patients) were included. Response was achieved in 60% (95% CI, 54–67%) in the short term (8–14 weeks); 64% (57–71%) in the medium term (16–24 weeks); and 64% (52–74%) in the long term (48–52 weeks). Remission was achieved in 37% (28–46%) in the short term; 42% (36–49%) in the medium term; and 45% (37–53%) in the long term. The endoscopic remission rate was 33% (25–40%) in the long term. Eighteen percent of patients lost response during follow-up. Nearly one-third of the patients needed dose optimisation, and in 59% of them it was effective. Twenty-five percent of patients developed adverse events, leading to treatment withdrawal in seven percent of the cases. (4) Conclusions: Ustekinumab is an effective and safe therapy in real-world refractory CD patients. Dose optimisation is frequently required, being effective in a high percentage of cases.

Summary Background and Aims Patients with colonic inflammatory bowel disease (IBD) have a high risk of colorectal cancer (CRC). Current guidelines recommend endoscopic surveillance, yet epidemiological studies show poor compliance. The aims of our study were to analyse adherence to endoscopic surveillance, its impact on advanced colorectal lesions, and risk factors of non‐adherence. Methods A retrospective multicentre study of IBD patients with criteria for CRC surveillance, diagnosed between 2005 and 2008 and followed up to 2020, was performed. Following European guidelines, patients were stratified into risk groups and adherence was considered when surveillance was performed according to the recommendations (±1 year). Cox‐proportional regression analyses were used to compare the risk of lesions. p‐values below 0.05 were considered significant. Results A total of 1031 patients (732 ulcerative colitis, 259 Crohn’s disease and 40 indeterminate colitis; mean age of 36 ± 15 years) were recruited from 25 Spanish centres. Endoscopic screening was performed in 86% of cases. Adherence to guidelines was 27% (95% confidence interval, CI = 24–29). Advanced lesions and CRC were detected in 38 (4%) and 7 (0.7%) patients respectively. Adherence was associated with increased detection of advanced lesions (HR = 3.59; 95% CI = 1.3–10.1; p = 0.016). Risk of delay or non‐performance of endoscopic follow‐up was higher as risk groups increased (OR = 3.524; 95% CI = 2.462–5.044; p < 0.001 and OR = 4.291; 95%CI = 2.409–7.644; p < 0.001 for intermediate‐ and high‐ vs low‐risk groups). Conclusions Adherence to endoscopic surveillance allows earlier detection of advanced lesions but is low. Groups at higher risk of CRC are associated with lower adherence.

Background: The impact of biologics on the risk of postoperative complications (PC) in inflammatory bowel disease (IBD) is still an ongoing debate. This lack of evidence is more relevant for ustekinumab and vedolizumab. Aims: To evaluate the impact of biologics on the risk of PC. Methods: A retrospective study was performed in 37 centres. Patients treated with biologics within 12 weeks before surgery were considered “exposed”. The impact of the exposure on the risk of 30-day PC and the risk of infections was assessed by logistic regression and propensity score-matched analysis. Results: A total of 1535 surgeries were performed on 1370 patients. Of them, 711 surgeries were conducted in the exposed cohort (584 anti-TNF, 58 vedolizumab and 69 ustekinumab). In the multivariate analysis, male gender (OR: 1.5; 95% CI: 1.2–2.0), urgent surgery (OR: 1.6; 95% CI: 1.2–2.2), laparotomy approach (OR: 1.5; 95% CI: 1.1–1.9) and severe anaemia (OR: 1.8; 95% CI: 1.3–2.6) had higher risk of PC, while academic hospitals had significantly lower risk. Exposure to biologics (either anti-TNF, vedolizumab or ustekinumab) did not increase the risk of PC (OR: 1.2; 95% CI: 0.97–1.58), although it could be a risk factor for postoperative infections (OR 1.5; 95% CI: 1.03–2.27). Conclusion: Preoperative administration of biologics does not seem to be a risk factor for overall PC, although it may be so for postoperative infections.

Background Patients with colon Inflammatory Bowel Disease (IBD) have a higher risk of colorectal cancer (CRC) than general population. Current guidelines establish endoscopic surveillance recommendations; however, epidemiological studies show poor compliance. The main aim of our study was to analyse adherence to endoscopic surveillance guidelines. Secondary aim was to evaluate the prevalence and time-to advanced lesions or CRC. Methods Retrospective multicentre study of patients with IBD followed-up in the participating centres between 2005 and 2020, who were diagnosed of IBD between 2005 and 2008, with criteria for CRC surveillance. Patients with CRC before IBD diagnosis were excluded. The ECCO 2013–2017 guidelines were used to evaluate adherence. Adenomatous lesions with &gt;25% of villous component, &gt;1cm or with high-grade dysplasia or serrated lesions &gt;1cm or with any degree of dysplasia were considered advanced lesions. Software used for all analysis was R in its 3.6.1 version. Normality was checked with the Shapiro-Wilks test. Mean comparison was carried out using t-Student test while normality assumptions held true, otherwise, Mann-Whitney test. Time-to advanced lesions or CRC event between patients that had adherence to ECCO guidelines versus those who did not was performed through Kaplan-Meier and Log-rank test. P-values below 0.05 were considered significant. Results A total of 1004 (713 Ulcerative Colitis, 252 Crohn’s disease and 39 Indeterminate Colitis; 52% male) patients from 25 centres were recruited with a median age of 36 (26–47) years. 87% of all patients were included in the endoscopic surveillance programme. The main reasons for non-inclusion were the absence of indication by the physician (38%) and the presence of inflammatory activity (37%). Adherence to the first or subsequent surveillance colonoscopies was 45% and 61%, respectively, with a total adherence rate of 32%. Prevalence of advanced lesions or CRC was 4% and 7 cases of CRC were detected. Time-to-detection of these lesions since IBD diagnosis was significantly longer in non-adherent patients (13.4 + 1.3 vs13.04 + 1.7; p&lt;0.001). Adherence was associated to a higher detection of advanced lesions or CRC compared to non-adherent patients (HR: 1.97; IC: 1.02–3.79; p=0.043) (Figure 1). Conclusion Adherence to ECCO guidelines for endoscopic surveillance is low in this Southern European population. A higher and earlier detection of advanced lesions or CRC was identified in the adherent group. The results of this study highlight the need to improve compliance with the recommendations to obtain better outcomes.

Ustekinumab has shown efficacy in Crohn’s Disease (CD) patients. To identify patient profiles of those who benefit the most from this treatment would help to position this drug in the therapeutic paradigm of CD and generate hypotheses for future trials. The objective of this analysis was to determine whether baseline patient characteristics are predictive of remission and the drug durability of ustekinumab, and whether its positioning with respect to prior use of biologics has a significant effect after correcting for disease severity and phenotype at baseline using interpretable machine learning. Patients’ data from SUSTAIN, a retrospective multicenter single-arm cohort study, were used. Disease phenotype, baseline laboratory data, and prior treatment characteristics were documented. Clinical remission was defined as the Harvey Bradshaw Index ≤ 4 and was tracked longitudinally. Drug durability was defined as the time until a patient discontinued treatment. A total of 439 participants from 60 centers were included and a total of 20 baseline covariates considered. Less exposure to previous biologics had a positive effect on remission, even after controlling for baseline disease severity using a non-linear, additive, multivariable model. Additionally, age, body mass index, and fecal calprotectin at baseline were found to be statistically significant as independent negative risk factors for both remission and drug survival, with further risk factors identified for remission.

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