Abstract Background Vedolizumab is effective for moderate-severe Ulcerative Colitis (UC), but predictive markers for long-term response are limited. This study aimed to profile circulating cytokines linked to inflammatory bowel disease (IBD) pathophysiology to identify immune predictive markers of vedolizumab response in UC patients. Secondary objectives included analyzing associations between baseline characteristics—such as smoking, disease duration, prior biologic exposure, and initial faecal calprotectin (FCP) and C-reactive protein (CRP) levels—and treatment response. Methods This retrospective, single-centre cohort study included 28 UC patients with inflammation objectified by clinical and biochemical data who initiated vedolizumab from 2015 to 2022. Blood samples were collected before treatment, and responses were evaluated at follow-up. Clinical remission (pMAYO < 3 with no subscore >1) with biochemical response (≥50% reduction in FCP and/or CRP) defined positive response. Endoscopic response was assessed in patients with available colonoscopy (endoscopic Mayo 0-1). Cytokines were measured via Magpix® Luminex with a Milliplex® T Cell Magnetic Bead Panel including 13 cytokines (IFN-gamma, IL8, IL12, IL13, IL17A, IL10, IL2, IL21, IL23, IL7, TNF-alpha, IL6, IL-1β). Results Twenty-eight patients with UC (100% pancolitis or left colitis) and S2+S3 94.7% were included in the study. 85.2% werebioexposed (infliximab in 75%). 50% of patients received concomitant corticosteroid therapy at the start of vedolizumab. Vedolizumab response was seen in 13 patients (46.4%) after a median overall treatment duration in both cohorts of 2.79 years (IQR7.55). The responder group was on vedolizumab treatment for a median of 5.58 (IQR 6.9) years vs 1.17 (IQR 5.13) years in the nonrespondergroup, p=0.005. There were no baseline differences between responders in pMayo or in FCP and CRP values. Activesmoking, disease duration until vedolizumab initiation and previous exposure to other biologics were not associated withresponse/non-response to vedolizumab treatment. Vedolizumab responders had significantly lower median interleukin 8 (IL8) levels at baseline than vedolizumab non-responders(median IL8 1.67 pg/mL versus 3.03 pg/mL, p=0.016). No statistically significant differences in baseline concentrations were found inany of the other interleukins analysed. Conclusion In our series of UC patients treated with vedolizumab, patients with long-term response to the drug show lower plasma IL8 levels than non-responders at baseline. Therefore, IL8 could serve as a predictive marker of long-term response to vedolizumab inUC patients. These results should be confirmed in prospective studies with larger sample sizes. References 1.Soendergaard C, Seidelin JB, Steenholdt C, Nielsen OH. Putative biomarkers of vedolizumab resistance and underlying inflammatory pathways involved in IBD. BMJ Open Gastroenterol. 2018 May 31;5(1):e000208. doi: 10.1136/bmjgast-2018-000208 2.Cotton JA, Platnich JM, Muruve DA, Jijon H, Buret AG, Beck PL. Interleukin-8 in gastrointestinal inflammation and malignancy: induction and clinical consequences. International Journal of Interferon, Cytokine and Mediator Research. 2016;8:13-34https://doi.org/10.2147/IJICMR.S63682 3.Grimm MC, Elsbury SK, Pavli P, Doe WF. Interleukin 8: cells of origin in inflammatory bowel disease. Gut. 1996 Jan;38(1):90-8. doi: 10.1136/gut.38.1.90 4.Bazzichetto C, Milella M, Zampiva I, Simionato F, Amoreo CA, Buglioni S, Pacelli C, Le Pera L, Colombo T, Bria E, Zeuli M, Del Bufalo D, Sperduti I, Conciatori F. Interleukin-8 in Colorectal Cancer: A Systematic Review and Meta-Analysis of Its Potential Role as a Prognostic Biomarker. Biomedicines. 2022 Oct 19;10(10):2631. doi: 10.3390/biomedicines10102631. 5.Nielsen OH, Rüdiger N, Gaustadnes M, Horn T. Intestinal interleukin-8 concentration and gene expression in inflammatory bowel disease. Scand J Gastroenterol. 1997 Oct;32(10):1028-34. doi: 10.3109/00365529709011220. 6.Bertani L, Caviglia GP, Antonioli L, Pellicano R, Fagoonee S, Astegiano M, Saracco GM, Bugianesi E, Blandizzi C, Costa F, Ribaldone DG. Serum Interleukin-6 and -8 as Predictors of Response to Vedolizumab in Inflammatory Bowel Diseases. J Clin Med. 2020 May 2;9(5):1323. doi: 10.3390/jcm9051323.

Background/Objectives: Crohn’s disease (CD) is a chronic immune-mediated disorder with heterogeneous response to biologic therapies. Ustekinumab (UST), an anti-IL-12/23 monoclonal antibody, is effective in CD, but predictive biomarkers of treatment response remain lacking. This study aimed to investigate cytokine dynamics during UST induction and to evaluate their association with clinical and biochemical outcomes in an observational cohort of CD patients. Methods: We prospectively recruited 31 adult patients with moderate-to-severe active CD initiating UST therapy at a tertiary referral center. Peripheral blood and stool samples were collected at baseline and weeks 4, 8, and 16. UST trough concentrations, C-reactive protein (CRP), fecal calprotectin (FC), hemoglobin, albumin, and 13 serum cytokines (including IL-1β, IL-6, IL-8, IL-10, IL-12p70, IL-13, IL-17, IL-23, TNF-α, and OSM) were analyzed. Response was defined as a ≥70% reduction in FC at week 16, or, alternatively, CRP < 5 mg/L or a Harvey–Bradshaw Index < 3. Results: Eighteen patients (58%) achieved response at week 16. Responders showed significant reductions in FC, CRP, and disease activity, while non-responders exhibited limited biochemical improvement. Overall, UST induction was associated with a global decrease in proinflammatory cytokines, particularly TNF-α and IL-1β. Responders displayed distinct cytokine patterns, with higher IL-13 levels at week 8 and lower IL-8 concentrations at week 16 compared with non-responders. UST trough levels tended to be higher in responders, and inverse correlations were observed between drug concentrations and several cytokines, including IL-6, IL-8, IL-13, and IL-23. Conclusions: UST induction leads to measurable immunological changes in CD, with differential cytokine dynamics distinguishing responders from non-responders. These findings support the potential of cytokine signatures, in combination with therapeutic drug monitoring, as pharmacodynamic biomarkers to optimize personalized treatment strategies in CD.

Abstract Background The PROTDILAT study (Loras et al. Lancet Gastroenterol Hepatol.2022) at 1-year follow-up showed greater efficacy of EBD vs SEMS for the treatment of short strictures in CD. Aims To assess the long-term evolution of patients included in PROTDILAT study. 1)Percentage of patients free of surgery; 2)Factors related to surgery; 3)Need for endoscopic retreatments; 4)Effectiveness related to the type of initial endoscopic treatment (EBD vs SEMS); 5)Complications related to endoscopic or surgical treatment. Methods Retrospective study based on PROTDILAT trial database (patients with CD, obstructive symptoms, with stenosis <10cm). Data on medical, endoscopic and surgical treatment and smoking habits were collected. The effectiveness of endoscopic treatment is defined by the percentage of patients free of surgery and endoscopic retreatment at the end of follow-up. Results Information available on 80/80 patients (39 SEMS, 41 EBD), 39 women, age (median): 45y (IQR: 38-55); median stricture length 3.4cm (IQR: 2-5.5), 42.5% being anastomotic. Thirty percent (24/80) of patients required surgical resection [(median time to surgery 27.88 months (5.89-52.39)]. Factors associated to surgery: non- intensification of therapy (HR 0.23 (0.09-063)), treatment with EBD (HR 0.24 (0.09-0.7)) (with respect to treatment with EBD + SEMS) and number of stents (HR 2.88 (1.14-7.27)). Of the 56 patients free of surgery, during the entire follow-up (median 84 months (74.7-84.0)), a median of 2 endoscopic procedures (1-3) were performed: EBD in 45 cases (80.0%) and SEMS in 26 cases (46%). Thirty-eight-point seventy-five percent (31/80 patients) did not require neither surgery nor endoscopic retreatment during the follow-up. Out of 44/80 patients (16 SEMS vs 28 EBD) with primary treatment success in PROTDILAT study (1 year of follow-up) that not required surgery, the long-term effectiveness of endoscopic treatment was 56% for SEMS and 68% for EBD (p=0.4). The complications related to endoscopic or surgical treatment were 8.75% (7/80) versus 37.5% (9/24) respectively (p=0.002). Conclusion Endoscopic treatment (predominantly EBD) avoids surgery in most cases, requiring a low number of endoscopic treatments in the long-term. Patients at higher risk for surgery are those with a greater number of endoscopic treatments that include SEMS and EBD. On the contrary, protective factors are non-intensification of therapy and having been treated exclusively with EBD. Although there are no significant differences in the long effectiveness between SEMS and EBD, a trend for a better outcome is observed for EBD. To highlight a significant higher rate of complications observed in surgical treatment compared to endoscopic treatment.

Abstract Background Ustekinumab (UST) is an effective treatment for Crohn's disease (CD) and ulcerative colitis (UC). However, some patients do not respond to conventional subcutaneous (SC) doses and lose response at follow-up. The use of maintenance intravenous (IV) UST could play a role in these patients. Methods The aim of the study was to evaluate the effectiveness of IV maintenance UST in patients with failure to subcutaneous UST. Single-center study performed in consecutive patients included in a prospective database. The reduction of activity markers such as C Reactive Protein (CRP) and fecal calprotectin (FC), UST trough levels pre- and post IV maintenance as well as clinical indices of activity were evaluated. IV dose adjustments and their effect on levels were collected. We defined biochemical remission as the percentage decrease FC ≥ 80% and/or final FC ≤ 250. Results Of 335 patients in our center under treatment with ustekinumab, 31 patients (9.25%) were included. Baseline characteristics of patients are shown in Table 1. Mean age at the start of UST IV 42.49 years ± 13.23. CD 77.4%; UC 22.6%. Up to 2/3 of patients with CD had a complicated phenotype (B2/B3) and 50% perianal disease (PD). All included patients were bio-exposed and 61.3% had carried ≥ 2 biologics. The major indication for initiation of UST was secondary failure to previous biologic therapy (74.2%). The most used induction IV dose was 390mg and subsequent SC maintenance was every 8 weeks in 76% (60% were later intensification cases). Re-induction was performed in 36.7% of patients. The median time from drug initiation to IV maintenance was 10.23 [IQR 30.7] months. In 54.8% a higher dose was administered in the first IV maintenance infusion. The most common maintenance regimen was 130mg (64.5%) every 4 weeks (54.8%). Baseline FC decreased significantly (Figure 1) at the end of follow-up (median [IQR]: 809 µg/g [2256] vs 333 µg/g [508], p =0.001). Basal Harvey index was reduced compared to HBI at 24 weeks (mean ± SD: 6.5 ± 4.3 vs 4.1 ± 3.1, p =0.019). Drug levels at the start of IV maintenance were 1.4 µg/ml [IQR 2.3] vs. 4.8 µg/ml [IQR 3.9] at week 24 (p< 0.001) after dose adjustment in 35.5% of patients during IV maintenance. At the end of follow-up 54% went into biochemical remission. The presence of PD was associated with lower biochemical remission (70.6% vs. 27.3%, p =0.025). The median IV UST maintenance time was 8.55 [IQR 23.9] months. 96.6% are continuing treatment. No serious infections or malignancy were documented. Conclusion The use of maintenance IV UST appears to be an effective and safe strategy that can be evaluated as a salvage treatment especially in highly bioexposed patients or with complex CD phenotype.

Background and Aims Switching from intravenous infliximab (IV-IFX) to subcutaneous biosimilar infliximab (SC-IFX) has been shown to safely maintain clinical remission and increase drug levels in patients with Crohn's disease (CD) and ulcerative colitis (UC). The aim of this study was to evaluate long-term outcomes after switching from IV-IFX to SC-IFX, including the drug concentration thresholds for maintaining remission and other predictors for loss of response after the switch.Methods This multicenter observational study involved CD and UC patients who were in clinical remission for at least 24 weeks and were scheduled to switch from IV-IFX to SC-IFX.Results Two hundred and twenty patients were included (74 UC [34%] and 146 CD [66%]). IV-IFX was administered for 52.5 months (range 25-89). Before switch, 106 (49%) patients were receiving intensified IV-IFX. While SC-IFX levels significantly increased following the switch from IV-IFX to SC-IFX, clinical parameters, C-reactive protein, and fecal calprotectin remained unchanged during follow-up. SC-IFX levels were significantly higher in patients receiving the standard IV-IFX dose than in those receiving the intensified dose. Immunomodulatory therapy at baseline and perianal disease had no effect on IFX trough levels, whereas higher body mass index was associated with increased levels. The suggested optimal SC-IFX cutoff concentration for clinical and biochemical remissions based on receiver operating characteristic analysis was 12.2 mu g/mL (area under the curve [AUC]: 0.62) at Week 12 and 13.2 mu g/mL (AUC: 0.57) at Week 52. Drug persistence was 92% at Week 52, with a good safety profile.Conclusions Switching from IV-IFX to SC-IFX safely maintains long-term remission in patients with CD and UC. In maintenance, the optimal cutoff point associated with remission was 12-13 mu g/mL.

BACKGROUND AND AIMS:Ustekinumab is an effective treatment for inflammatory bowel diseases. However, some patients do not respond to conventional doses. The aim of the study was to evaluate the effectiveness of intravenous maintenance ustekinumab in patients with secondary failure. METHODS:Single-center, retrospective study in adult patients with intravenous maintenance ustekinumab. The reduction of biochemical activity markers, ustekinumab trough levels and clinical indices of activity were evaluated. Biological remission was defined as the percentage decrease fecal calprotectin ≥80% and/or final fecal calprotectin ≤250 and C reactive protein <5mg/L. RESULTS:Thirty-one patients were included: Crohn's disease 77.4%. All included patients were bio-exposed and 61.3% had carried ≥2 biologics. Pre-intravenous maintenance mean Harvey-Bradshaw Index was 6.5±4.38 vs 5±3.1 at week 8 (p=0.024) vs 4.1±3.1 at week 24 (p=0.019). The median ustekinumab trough level pre-intravenous maintenance was 1.40μg/ml [IQR 2.3] vs 5.35μg/ml [IQR 4.1] at week 8 (p<0.001) vs 4.8μg/ml [IQR 3.9] at week 24 (p<0.001). The pre-intravenous maintenance median fecal calprotectin was 809μg/g [IQR: 2256] vs 423μg/g [IQR: 999] at week 8 (p=0.025) vs 333μg/g [508] (p=0.001) at week 24. At the end of follow-up 48% went into biological remission. The presence of perianal disease was associated with lower biological remission (70.6% vs 27.3%, p=0.025). Median intravenous ustekinumab maintenance time was 8.55 [IQR 23.9] months. In 83.9% of patients no serious infections or malignancy were documented. CONCLUSIONS:The use of maintenance intravenous ustekinumab appears to be an effective and safe strategy that can be evaluated as a salvage treatment especially in highly bio-exposed patients.

INTRODUCTION:Intra-abdominal abscesses complicating Crohn's disease [CD] are a challenging situation. Their management, during hospitalisation and after resolution, is still unclear. METHODS:Adult patients with CD complicated with intra-abdominal abscess. who required hospitalisation, were included from the prospectively maintained ENEIDA registry from GETECCU. Initial strategy effectiveness and safety to resolve abscess was assessed. Survival analysis was performed to evaluate recurrence risk. Predictive factors associated with resolution were evaluated by multivariate regression and predictive factors associated with recurrence were assessed by Cox regression. RESULTS:In all, 520 patients from 37 Spanish hospitals were included; 322 [63%] were initially treated with antibiotics alone, 128 [26%] with percutaneous drainage, and 54 [17%] with surgical drainage. The size of the abscess was critical to the effectiveness of each treatment. In abscesses < 30 mm, the antibiotic was as effective as percutaneous or surgical drainage. However, in larger abscesses, percutaneous or surgical drainage was superior. In abscesses > 50 mm, surgery was superior to percutaneous drainage, although it was associated with a higher complication rate. After abscess resolution, luminal resection was associated with a lower 1-year abscess recurrence risk [HR 0.43, 95% CI 0.24-0.76]. However, those patients who initiated anti-TNF therapy had a similar recurrence risk whether luminal resection had been performed. CONCLUSIONS:Small abscesses [<30mm] can be managed with antibiotics alone; larger ones require drainage. Percutaneous drainage will be effective and safer than surgery in many cases. After discharge, anti-TNF therapy reduces abscess recurrence risk in a similar way to bowel resection.

Abstract Background Ustekinumab (UST), an inhibitor of the p40 subunit of interleukins 12 and 23, is approved for the treatment of moderate and severe Crohn disease (CD) but a significant number of patients either partially respond or do not benefit at all. Therapeutic drug monitoring can be used to optimize the efficacy of biological drugs by ensuring adequate exposure to these drugs. The aim of our research was to identify the relationship between serum concentrations of UST during the induction and biochemical remission at week 16 in patients with CD. Methods All CD patients treated with UST included in a local database were identified. Only patients with a fecal calprotectin (FCP) > 250 mg/g were selected. All patients were treated with an initial intravenous induction therapy of UST, followed by subcutaneous maintenance therapy. Disease activity was assessed retrospectively by clinical (Harvey–Bradshaw Index [HBI]) and biochemical parameters (FCP; C-reactive protein (CRP) and Albumin) at Week 0, Week 4, week 8 and week 16. UST trough levels were measured at 4, 8 and 16 weeks using a commercially available validated enzyme-linked immunosorbent assay (ELISA). Main outcome was biochemical remission, defined by a decreased of calprotectin levels more than 80% or an absolute value less than 200 mg/g at week 16. Results Seventy-six patients were included. Patients’ Characteristics at baseline are listed in table 1. Median [IQR] HBI was 5,5 [3-8] at the beginning of treatment. Evolution of biochemical parameters throughout induction is showed in table 2. At the end of the induction phase (week 16), HBI, CRP and FCP decreased significantly from baseline. At this moment HBI was less than 2 in 51% of patients. FCP was available in 63 patients. Biochemical remission was observed in 26/63 (41,3%) patients. Median [IQR] UST serum concentrations were 20,9 μg/mL [13,7–26,3] at w4, 10,1 μg/mL [3,5–7,4] at w8 and 4,1 μg/mL [1,4–3,9] at w16. Quartile analysis demonstrated that 100% and 66% with an UST serum concentration in the highest quartile [Q4], at w4 and w8, achieved a biochemical remission by w16 [p = 0.05 and p <0,02 respectively]. The area under the receiving operating characteristic curve (AUROC) of UST levels to predict biochemical remission at week 4 and week 8 were 0,84 CI95% (0,62-1) and 0,74 CI95% (0,57-0,91) respectively. Conclusion Serum concentrations of UST at week 4 and 8 after intravenous infusion could be used to stratify patients according to the probability of achieving remission. This measurements during induction could be used to optimize treatment of CD.

Background Stenosis is one of the most common complications in patients with Crohn’s disease (CD). Endoscopic balloon dilation (EBD) is the treatment of choice for a short stenosis adjacent to the anastomosis from previous surgery. Self-expandable metal stents (SEMS) may be a suitable treatment option for longer stenoses. To date, however, there is no scientific evidence as to whether endoscopic (EBD/SEMS) or surgical treatment is the best approach for de novo or primary stenoses that are less than 10 cm in length. Methods/design Exploratory study as “proof-of-concept”, multicentre, open-label, randomized trial of the treatment of de novo stenosis in the CD; endoscopic treatment (EBD/SEMS) vs surgical resection (SR). The type of endoscopic treatment will initially be with EDB; if a therapeutic failure occurs, then a SEMS will be placed. We estimate 2 years of recruitment and 1 year of follow-up for the assessment of quality of life, costs, complications, and clinical recurrence. After the end of the study, patients will be followed up for 3 years to re-evaluate the variables over the long term. Forty patients with de novo stenosis in CD will be recruited from 15 hospitals in Spain and will be randomly assigned to the endoscopic or surgical treatment groups. The primary aim will be the evaluation of the patient quality of life at 1 year follow-up (% of patients with an increase of 30 points in the 32-item Inflammatory Bowel Disease Questionnaire (IBDQ-32). The secondary aim will be evaluation of the clinical recurrence rate, complications, and costs of both treatments at 1-year follow-up. Discussion The ENDOCIR trial has been designed to determine whether an endoscopic or surgical approach is therapeutically superior in the treatment of de novo stenosis in CD. Trial registration ClinicalTrials.gov NCT 04330846. Registered on 1 April 1 2020. https://clinicaltrials.gov/ct2/home

Abstract Background There are limited data in real-life of ustekinumab (USK) used in ulcerative colitis (UC). The aim of this study was to assess the effectiveness and safety in clinical practice of USK in UC in the medium and long-term. Methods Observational study in UC patients who received USK at the recommended dose based on weight ~6 mg/kg IV week, 0.90 mg SC week, 8 and maintenance, 90 mg SC every, 8 or, 12 weeks and with, 1 year of follow-up. The partial Mayo score (PMS) was used to assess clinical remission (PMS≤, 2). The PMS, C-reactive protein (CRP) and faecal calprotectin (FC) values ​​were recorded at baseline and after, 8, 16, 24 and, 52 weeks. Dose adjustment was performed by the measure of UST trough levels by ELISA, when patient lost clinical and/or biochemical response and the levels were low (<1.3 µg/ml). Demographic, clinical, biochemical and endoscopic data, previous treatments, adverse events (AEs), surgeries and hospitalizations, were documented. Results Twenty-three patients with UC were analysed. (Table, 1). All patients had received previous biological treatment:, 52% ≥2 anti-TNF, 65% vedolizumab and, 30% JAK inhibitors. Treatment discontinuation occurred in, 3 patients (13%). The persistence was, 83% and, 79% at, 6 and, 12 months (Figure, 1). During follow-up, 12 patients (52%) maintained standard dose of USK. Dose adjustment was performed in, 13 patients (56%):, 3 (13%) required intravenous UST reinduction and, 10 (43%) required dose escalation (8 by shortening the interval between doses and, 2 by switching to intravenous USK administration). Clinical remission was reached in, 61%, 58%, 56%, 79% of the patients after, 8, 16, 24, 52 weeks, respectively. Normal CRP (<5mg/L) and FC (<150 µg/g) levels were achieved in, 76%, 93% and, 80% and in, 35%, 31% and, 40% of patients after, 8, 24, 52 weeks, respectively. Five of, 6 patients who had endoscopy before and after treatment showed endoscopic Mayo subscore ≤1. There were, 2 AEs, 1 hospitalization, and, 1 colectomy during follow-up. Conclusion This study demonstrates the safety as well as the clinical, biological and endoscopic effectiveness of USK adjusted by levels in real life in a highly refractory UC cohort.

INTRODUCTION: MicroRNAs (miRNAs) are important epigenetic regulators in Crohn's disease (CD); however, their contribution to postoperative recurrence (POR) is still unknown. We aimed to characterize the potential role of miRNAs in predicting POR in patients with CD and to identify their pathogenic implications. METHODS: Of 67 consecutively operated patients with CD, we included 44 with pure ileal CD. Peripheral blood samples were taken before surgery and during follow-up. The patients were classified according to the presence or absence of POR assessed by ileocolonoscopy or magnetic resonance imaging enterography. The miRNAs were profiled by reverse transcription polymerase chain reaction before surgery and during morphological POR or, for those who remained in remission, 1 year after surgery. R software and mirWalk were used. RESULTS: Five human miRNAs (miR-191-5p, miR-15b-5p, miR-106b-5p, miR-451a, and miR-93-5p) were selected for discriminating between the 2 patient groups at presurgery (PS), with an area under the curve of 0.88 (95% confidence interval [0.79, 0.98]). Another 5 (miR-15b-5p, miR-451a, miR-93-5p, miR-423-5p, and miR-125b-5p) were selected for 1 year, with an area under the curve of 0.96 (95% confidence interval [0.91, 1.0]). We also created nomograms for POR risk estimation. CCND2 and BCL9L genes were related to PS miRNA profiles; SENP5 and AKT3 genes were related to PS and 1 year; and SUV39H1 and MAPK3K10 were related to 1 year. DISCUSSION: Different plasma miRNA signatures identify patients at high POR risk, which could help optimize patient outcomes. We developed nomograms to facilitate the clinical use of these results. The identified miRNAs participate in apoptosis, autophagy, proinflammatory immunological T-cell clusters, and reactive oxygen species metabolism.

Abstract Background Ustekinumab (UST) intensification during Crohn’s Disease (CD) treatment is becoming common in clinical practice. Little is known about early intensification maintenance regimens and their drug levels utility in discriminating CD-response and the need for further intensification. We aim to analyze UST levels’ evolution in an intensified maintenance regimen, their capacity to discriminate response according to inflammatory parameters and indicate the need for further intensification. Methods This is a retrospective study with 43 moderate/severe active CD patients (Harvey-Bradshaw Index [HBI] ≥4 and Fecal Calprotectin [FC] >250 µg/g) who received UST induction treatment (induction dose of 6mg/kg IV, plus dose of 90mg SC at week 8). Patients received maintenance treatment (90mg SC/8 weeks) and were followed for 52 weeks. They were classified according to the response obtained at the first year in responders (R), HBI <3 and FC <200µg/g; non-responders (NR), HBI ≥4 and FC >250µg/g; and intensification group (IG), partially responders that needed UST intensification to every 4 weeks. HBI, FC, C-Reactive Protein (CRP), and UST levels data were collected at baseline (w0), week 8 (w8), week 16 (w16), and 52 weeks (w52) of maintenance. IG was followed 12–26 weeks after intensification (aI). Results Half of the patients (48.8%) were male. Most of them (97.7%) have received previous anti-TNF-α treatment (53.49% ≥2 anti-TNF-α). Patients’ median age at the moment of starting UST was 51 (37.5, 58.5) years. Median disease duration was 11 (7.5, 23) years. Location of disease was ileal in 30% of patients and ileocolic in 53%. One-third of patients suffered perianal disease, and 41 % were smokers. The only demographic factor associated with non-response was ileocolic location. Table 1 shows the evolution of inflammatory parameters and UST levels according to the response. A Pearson correlation (r=0.62) between higher FC drop (baseline-w16) and higher drug levels at w16 was observed. The evolution of biological markers discriminates NR during induction; however, neither biological markers nor UST level can distinguish between R and those who will need intensification. R shows higher UST levels at w52 compared to IG. IG showed a significant increase of UST levels (mean of 5.39 points) and a substantial drop of FC and HBI (mean of 115.62 and 2.27 points, respectively) after intensification. Those patients reported clinical improvement; however, they could not reach a FC <250µg/g, which could need a more extended period to decrease. Conclusion FC drop-slope is associated with higher levels of UST at the end of induction. UST levels at w52 are useful for discriminating patients who will benefit from UST intensification every 4 weeks.

Golimumab has demonstrated its long-term efficacy and safety in ulcerative colitis in clinical trials, but no data of long-term persistence has been published from real world. To estimate long-term persistence of golimumab, as well as factors associated with longer persistence, in patients with ulcerative colitis in real life. Observational multicentre study including adult patients with ulcerative colitis treated with golimumab and with at least twelve months of follow-up. We included 190 patients, 105 (55.26%) naive to anti-TNF, with mean disease duration of 9.32 ± 8.09 years. Probability of persistence was 63%, 46%, 39% and 27% at 1, 2, 3 and 4 years, respectively. Persistence was lower in patients with primary failure to previous anti-TNF. Eighty-two (43.16%) patients needed dose intensification during follow-up, with a mean time until intensification of 8.03 ± 8.64 months. Dose intensification and lower disease duration predicted higher persistence with golimumab (p = 0.037 and p = 0.008, respectively). During a follow-up of 17.25 ± 15.83 months, 32 (16.5%) patients needed hospitalisation and 11 (6%) underwent colectomy. No unexpected adverse events were reported. Golimumab has demonstrated good persistence and safety profile for long treatment in ulcerative colitis patients.

Hasta el 50% de los pacientes con enfermedad inflamatoria intestinal (EII) presentan algún tipo de manifestación extraintestinal (MEI) asociada, presentándose las más frecuentes en articulaciones, piel, ojos y vía biliar. Se producen con mayor frecuencia en la enfermedad de Crohn (EC) que en la colitis ulcerosa (CU), particularmente en la EC de colon y en la enfermedad perianal. La mayoría de las MEI tienen una actividad paralela a la de la propia EII, con excepción de la espondiloartropatía, la uveítis, el pioderma gangrenoso y la colangitis esclerosante primaria. Las manifestaciones clínicas dependen del tipo de MEI y de la actividad de la enfermedad de base. En general, el tratamiento de las MEI se basa en el control de la actividad inflamatoria intestinal; sin embargo, algunas pueden preceder al diagnóstico de la propia EII y/o presentar un curso independiente, requiriendo tratamiento específico. Los pacientes con EII y MEI asociadas son pacientes especialmente complejos, por lo que resulta imprescindible un abordaje multidisciplinar tanto para la evaluación como para la selección del tratamiento más adecuado.