Background:Inflammatory pouch disorders can be refractory to conventional therapy. Evidence on biological therapy from large cohorts is scarce. Objective:To explore the use and effectiveness of biological therapy for inflammatory pouch disorders. Design:A retrospective and multicentre study. Methods:We included patients diagnosed with pouchitis, Crohn's Disease of the Pouch (CDP) or cuffitis and treated with biological therapy. Effectiveness was evaluated at 12 months based on normalisation of stool frequency, absence of pain, faecal urgency or fistula discharge (clinical remission), or as any improvement in these symptoms (clinical response). We also compared the effectiveness of a second biologic after anti-tumour necrosis factor (anti-TNF) failure using descriptive and comparative statistics. Results:In total, 145 patients were included; 62% were men and the median age was 54 (20-71) years. Overall, 212 lines of treatment were evaluated (95 infliximab, 69 adalimumab, 7 golimumab, 35 vedolizumab and 26 ustekinumab). At least a second line of treatment was received by 41% of patients. Overall, 66% had chronic pouchitis and 29% had CDP. Clinical remission rates at 12 months were 45%, 44%, 43%, 39% and 45% for infliximab, adalimumab, golimumab, vedolizumab and ustekinumab, respectively. No differences were found based on the type of disease. Vedolizumab was the only treatment to show better results as a first-line therapy (50% vs 33%, p < 0.05). Thirty-nine patients received a second therapy after anti-TNF failure. Second anti-TNF use had higher risks of failure (odds ratio (OR) 4.8, 95% confidence interval (CI) 2.3-19) and discontinuation (OR 5.52, 95% CI 1.94-25.5). Conclusion:Biological therapy is a cornerstone in the treatment of pouch disorders, demonstrating consistently high effectiveness. After anti-TNF failure, another mechanism of action should be employed.

BACKGROUND & AIMS:The availability of biologicals has been associated with a decreased rate of first intestinal resection in patients with Crohn's disease (CD). However, its impact on postoperative recurrence (POR) has received little attention. We aimed to assess time trends in the strategies for the management of postoperative CD and the rate of second surgeries over the past 3 decades. METHODS:Adult patients with CD who had undergone a first ileocolic resection between 1990 and 2020 were identified from the Spanish ENEIDA registry. Patients were grouped by date of surgery as follows: before the biological era ([BB] 1990-2000), in the early biological era ([EB] 2000-2010), and in the widespread biological era ([WB] 2011-2020). RESULTS:A total of 4890 patients were included (23% BB, 38% EB, and 39% WB). A significant increase in medical prevention of POR with both thiopurines (BB, 12%; EB, 47%; and WB, 37%; P < .001) and biological agents (BB, 0%; EB, 9%; and WB, 37%; P < .001) was observed. Medical treatment with biologicals for POR also increased (BB, 35%; EB, 48%; and WB, 43%; P < .001). The cumulative surgical POR-free survival rate at 5 and 10 years was significantly higher in both the EB and WB cohorts as compared with the BB cohort (BB, 92% and 83%; EB, 96% and 90%; WB, 97% and 91%, respectively; P < .001). CONCLUSIONS:Medical prevention for POR after the first intestinal resection for CD increased significantly in the past 2 decades, alongside the use of biologicals to treat POR. These changes were associated with a significant decrease in the cumulative probability of surgical POR.

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.

BACKGROUND:Oral corticosteroids remain the treatment of choice for moderately active ulcerative colitis (UC), achieving clinical remission in 30%-60% of patients. OBJECTIVE:To compare the rates of steroid-free clinical-endoscopic remission at weeks 8 and 54 in patients treated with 3 methyl-prednisolone pulses before oral corticosteroids in moderately active UC versus those only receiving oral corticosteroids. DESIGN:Prospective, open, multicentre, randomized, controlled trial. Patients with left/extensive, moderately active UC, naive to immunosuppressants and biological agents, were randomized to receive conventional treatment (CT) with oral prednisone 60 mg/day or the same regimen preceded by an additional daily pulse (AP) of 500 mg of methyl-prednisolone for 3 days. All patients who responded started oral mesalazine and were followed up until month 12 or clinical relapse. RESULTS:Seventy-five patients were randomized: 39 were allocated to the CT arm and 36 to the AP arm. Overall, 21 patients achieved clinical-endoscopic remission (28%; 95% confidence interval [CI]: 23%-33%) at both weeks 8 and 54 without needing rescue treatments, being not significantly different between both study groups (23% [95%CI: 14%-32%] CT vs. 33% [95%CI: 21%-45%] AP; P = 0.323). Patients in the AP group had higher rates of clinical response at day 3 and remission at day 7. No significant differences in adverse events were observed. Due to early termination, the study was underpowered, and findings should be interpreted as exploratory. CONCLUSIONS:The addition of 3 pulses of high-dose corticosteroids to a conventional regimen of oral prednisone does not improve medium and long-term clinical outcomes in moderately active UC. TRIAL REGISTRATION CODES:EudraCT number 2016-001170-15; ClinicalTrials.gov identifier NCT02921555.

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the digestive tract usually characterized by diarrhea, rectal bleeding, and abdominal pain. IBD includes Crohn’s disease and ulcerative colitis as the main entities. IBD is a debilitating condition that can lead to life-threatening complications, involving possible malignancy and surgery. The available therapies aim to achieve long-term remission and prevent disease progression. Biologics are bioengineered therapeutic drugs that mainly target proteins. Although they have revolutionized the treatment of IBD, their potential therapeutic benefits are limited due to large interindividual variability in clinical response in terms of efficacy and toxicity, resulting in high rates of long-term therapeutic failure. It is therefore important to find biomarkers that provide tailor-made treatment strategies that allow for patient stratification to maximize treatment benefits and minimize adverse events. Pharmacogenetics has the potential to optimize biologics selection in IBD by identifying genetic variants, specifically single nucleotide polymorphisms (SNPs), which are the underlying factors associated with an individual’s drug response. This review analyzes the current knowledge of genetic variants associated with biological agent response (infliximab, adalimumab, ustekinumab, and vedolizumab) in IBD. An online literature search in various databases was conducted. After applying the inclusion and exclusion criteria, 28 reports from the 1685 results were employed for the review. The most significant SNPs potentially useful as predictive biomarkers of treatment response are linked to immunity, cytokine production, and immunorecognition.

Background We aimed to (1) analyze the applicability of the updated Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE-II) recommendations in real-world clinical practice, (2) identify barriers to their implementation, and (3) propose practical measures to overcome these obstacles.Methods This qualitative study was based on a survey, a literature review, and expert opinions. Nine inflammatory bowel disease (IBD) experts identified 7 areas likely to be controversial or potential implementation barriers in daily clinical practice: endoscopy, histology, ultrasound, quality of life, biomarkers, symptom control, and patient-reported outcomes (PROs). Based on this, a survey was carried out among educational course participants. The experts discussed the literature review and survey results and proposed several statements and practical actions.Results A total of 55 gastroenterologists answered the survey. The reported difficulty level in reaching STRIDE-II treatment goals in clinical practice was high. Only 22% of participants performed clinical remission assessments using clinical indexes and PROs. Seventy percent of responders did not use fecal calprotectin cutoffs and considered changes from the previous levels instead. Mucosal healing as a long-term therapeutic goal was considered necessary to be individualized in specific patient subgroups (eg, elderly/fragile patients, multiple treatment failures, and last-line therapies). Other barriers, like the lack of access to imaging techniques or insufficient knowledge and skills among healthcare professionals, were detected. The experts suggested adding less stringent treatment goals and measurements, patient stratification, local adaptations, educational activities, and research.Conclusions STRIDE-II recommendations face various implementation barriers needing careful evaluation in order to enhance their adoption in clinical practice, and ultimately improve outcomes in IBD patients. Adherence to the updated Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE-II) recommendations is suboptimal in the real-world. Barriers related to healthcare professionals and systems, including shortages of trained personnel and limited access to endoscopy, must be considered. Tailored implementation strategies are necessary to enhance the quality of care and to increase adherence to the STRIDE-II recommendations: the definition of less stringent treatment goals and measurements, patient stratification, local adaptations, or educational activities. Graphical Abstract

Abstract Background The clinical efficacy of granulocyte and monocyte adsorptive apheresis (GMA) with Adacolumn in patients (pts) with inflammatory bowel disease (IBD) has been reported in several clinical trials (CT), with significant clinical remission rates. However, evidence on real-world effectiveness of GMA with Adacolumn in ulcerative colitis (UC) or Crohn's disease (CD) pts who were underrepresented in CT is still limited. Methods GRACE is a multicentric, prospective observational study conducted at 31 centres in Spain. The study included adults (≥18 years) diagnosed with UC or CD who had been scheduled to receive GMA with Adacolumn in clinical practice. The study consisted of a baseline (GMA initiation) and 3 follow-up visits at 4, 24, and 48 weeks after the last GMA session. The primary endpoint is the steroid-free remission rate at 24 weeks. This interim analysis is focused on clinical characterization of pts and their management and outcome 4 weeks after GMA treatment. Results A total of 95 evaluable pts were included at data cut-off date (25 Sept 2023) (median age: 54 years; 50% men: 81% outpatients). Overall, 89.4% (n=84) of pts had UC, being moderate-to-severe in 85.5%; 57,8% had pancolitis, and the median Mayo score was 5 (interquartile range [IQR], 3-6). Out of the 10 pts (10.6%) with CD, all had B1, and 3 pts had L1, 4 L2 and 3 L3. Overall, 17% had extraintestinal manifestations. Regarding IBD-related therapy, 52.6% of pts had previously received anti-TNF agents, 37.9% thiopurines, and 17.8% JAK inhibitors. Overall, 85.3% of pts received concomitant treatment with GMA, most commonly 5-ASA (60%), corticosteroids (51,6%), ustekinumab (20%), vedolizumab (17.9%), and anti-TNF therapy (11.6%). A total of 71 pts reached the 4-week visit after receiving a median of 10 (IQR, 8-10) GMA sessions (weekly: 26.3%, biweekly: 36.8%, and weekly/biweekly: 31.6%). At week 4, clinical remission was achieved by 50.7% of patients (UC: 49.2%; CD: 66.7%), being 50% and 53.3% in patients concomitantly treated with ustekinumab and vedolizumab. Steroid-free remission rate was 26.1% (UC: 22.2%; CD: 66.7%) at week 4. Overall, 11,2% of patients experienced AEs related to GMA, most of them being mild (73%) or moderate (22.4%). Most common AEs were headache and asthenia. No SAEs were observed. Conclusion Preliminary data at 4 weeks show that Adacolumn is a safe and effective treatment in a cohort of IBD refractory pts with previous failure to multiple therapies including thiopurines, biologics and JAK inhibitors. Half of pts were concomitantly treated with biologics, and their clinical remission rate was similar to the overall population. Long-term results of this study (48 weeks) are required to confirm these findings.

OBJECTIVE:Ustekinumab was recently approved for the treatment of moderate-to-severe ulcerative colitis (UC). Although data from the UNIFI clinical trial are encouraging, real-world data assessing effectiveness and safety are scarce. The aim of this study was to assess the effectiveness, safety and pharmacokinetics of ustekinumab in a large cohort of refractory UC patients. METHODS:Multicenter observational study of UC patients who received ustekinumab for active disease. The Partial Mayo Score (PMS), endoscopic activity, C-reactive protein (CRP) and faecal calprotectin (FC) were recorded at baseline and at different time points. Demographic and clinical data, adverse events (AEs) and surgeries were documented. RESULTS:A total of 108 patients were analyzed from 4 referral Spanish hospitals. The clinical remission rates were 59%, 56.5%, 57% and 69% of patients at weeks 8, 16, 24 and 52, respectively. Normalization of FC was achieved in 39.6%, 41% and 51% at weeks 8, 24 and 52, respectively. CRP normalization was observed in 79%, 75% and 76.5% of patients at weeks 8, 24 and 52, respectively. Fewer previous anti-TNF agents and loss of response to anti-TNF were associated with clinical response and normalization of FC, respectively. AEs were observed in 5 patients, and 9 underwent colectomy. Ustekinumab persistence rates were 91%, 83% and 81% at 24, 48 and 96 weeks, respectively. CONCLUSIONS:Ustekinumab demonstrated, in the real-world setting, long-term effectiveness and a favorable safety profile in a cohort of refractory UC patients.

BackgroundThe efficacy of ustekinumab and vedolizumab for treating complex perianal fistula in Crohn's disease has been barely studied. We aimed to assess treatment persistence, clinical remission, and safety of these drugs in this context.MethodsCrohn's disease patients who had received ustekinumab or vedolizumab for the indication of active complex perianal fistula, were included. Clinical remission was defined according to Fistula Drainage Assessment Index (no drainage through the fistula upon gentle pressure) based on physicians’ assessment.ResultsOf 155 patients, 136 received ustekinumab, and 35 vedolizumab (16 received both). Median follow-up for ustekinumab was 27 months. Among those on ustekinumab, 54 % achieved remission, and within this group, 27 % relapsed during follow-up. The incidence rate of relapse was 11 % per patient-year. Multivariate analysis found no variables associated with treatment discontinuation or relapse. Median follow-up time for patients receiving vedolizumab was 19 months. Remission was achieved in 46 % of the patients receiving vedolizumab, and among them, 20 % relapsed during follow-up. The incidence rate of relapse was 7 % per patient-year. Adverse events were mild in 6 % on ustekinumab and 8 % on vedolizumab.ConclusionUstekinumab and vedolizumab appear effective, achieving remission in around half of complex perianal fistula patients, with favorable safety profiles.

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 Despite research, there are still controversial areas in the management of Crohn’s disease (CD).Objective To establish practical recommendations on using anti-tumour necrosis factor (TNF) drugs in patients with moderate-to-severe CD.Methods Clinical controversies in the management of CD using anti-TNF therapies were identified. A comprehensive literature review was performed, and a national survey was launched to examine current clinical practices when using anti-TNF therapies. Their results were discussed by expert gastroenterologists within a nominal group meeting, and a set of statements was proposed and tested in a Delphi process.Results Qualitative study. The survey and Delphi process were sent to 244 CD-treating physicians (response rate: 58%). A total of 14 statements were generated. All but two achieved agreement. These statements cover: (1) use of first-line non-anti-TNF biological therapy; (2) role of HLA-DQA1*05 in daily practice; (3) attitudes in primary non-response and loss of response to anti-TNF therapy due to immunogenicity; (4) use of ustekinumab or vedolizumab if a change in action mechanism is warranted; (5) anti-TNF drug level monitoring; (6) combined therapy with an immunomodulator.Conclusion This document sought to pull together the best evidence, experts’ opinions, and treating physicians’ attitudes when using anti-TNF therapies in patients with CD.

Background and Aims: Inflammatory pouch disorders exhibit a heterogeneous clinical spectrum and therapeutic requirements have not been properly studied. Methods: This retrospective, multicentre study included ulcerative colitis patients with ileal pouch construction and were later diagnosed with an inflammatory pouch disorder between 1995 and 2020. Classifications, behaviour and therapies applied were recorded and compared in the long-term. Results: Overall, 338 patients were recruited. The most common disorders were pouchitis (n = 258, 76%), Crohn's disease of the pouch (n = 55, 16%) and cuffitis (n = 25, 7%). Pouchitis presented mainly as chronic (65.2%) and recurrent (87%) forms. Crohn's disease manifested as stricturing/penetrating in 53% of cases and perianal disease in 42%. Patients received multiple therapies: 86% antibiotics, 42% steroids, 27% immunosuppressants, 43% biologics and 27% surgery. Compared with pouchitis, Crohn's disease of the pouch was characterised by a later diagnosis (99 vs. 55 months, p < 0.001) and greater needs for immunosuppressants (OR 3.53, 1.79-6.94, p < 0.0001), biologics (OR 5.45, 2.78-10.6, p < 0.0001) and surgeries (OR 2.65, 1.43-4.89, p < 0.001). Conclusions: Chronic pouchitis is the most common pouch disorder presentation. These entities have diverse therapeutics requirements, particularly for Crohn's disease of the pouch.

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.

Abstract Background Oral corticosteroids remain as the first-line treatment for moderately active ulcerative colitis (UC). In controlled studies, they achieved clinical remission in 30-60% of patients at 30 days. In severe systemic diseases, intravenous bolus administration of methyl-prednisolone accelerates the clinical response and increases the therapeutic efficacy of corticosteroids. Aims To assess the additive effect of IV boluses of methyl-prednisolone in an outpatient Schedule on the remission rate of moderately active UC. Methods Randomized, controlled, open study. Inclusion criteria: 1) moderately active (complete May 6-10) distal or extensive UC; 2) never exposed to immunosuppressants or biologicals; 3) without corticosteroid therapy within the last 6 months. Randomization to oral prednisone 60mg/day (ORAL arm) or the same regimen preceded by intravenous boluses of 500mg methyl-prednisolone for 3 days (BOLUS arm). Primary endpoint: clinical and endoscopic remission at week 8 as defined by a complete Mayo score <3 with no subscore >1. Results are expressed in frequencies, medians and interquartile range. Results 75 patients (39 ORAL, 36 BOLUS) were included, 24% at diesease onset, 49% extensive UC, 68% were on maintenance with oral 5ASA, and 31% had ever received systemic corticosteroids. At baseline, complete Mayo score was 9 (7-9), with C-reactive protein 9.25 mg/L (3.85-20.17) and fecal calprotectin 1430 ug/g (501-2702), with no differences in the baseline clinical-epidemiological characteristics between both treatment arms. At 8 weeks, 37% of patients achieved clinical-endoscopic remission (47% BOLUS vs 28% ORAL; p=0.089), 52% mucosal healing -Mayo endoscopic subscore <2- (61% BOLUS vs 44% ORAL; p=0.129), 24% endoscopic remission -Mayo endoscopic=0- (31% BOLUS vs 18% ORAL; p=0.202) and 55% clinical remission - partial Mayo score <2- (61% BOLUS vs 49% ORAL; p=0.281). No associated factors with clinical-endoscopic remission were identified. Conclusion The addition of three intravenous megaboluses at the beginning of a conventional regimen of oral prednisone achieves a non-significant increase in clinical-endoscopic remission rates at the end of corticosteroid treatment in patients with moderately active UC.