Extensive Colitis Research Articles

Real-world clinical characteristics and therapeutic strategies in patients with moderate-to-severe inflammatory bowel disease in Argentina: Data from the RISE-AR study.

Real-world evidence on the adoption of different pharmacological strategies in inflammatory bowel disease (IBD) in Latin America is scarce. Herein, we describe real-world sociodemographic, clinical characteristics, and different therapeutic approaches used in patients with IBD in Argentina. RISE AR (NCT03488030) was a multicenter, non-interventional study with a cross-sectional evaluation and a 3-year retrospective chart review conducted in Argentina. Adult patients with a previous diagnosis of moderate-to-severe ulcerative colitis (UC) or Crohn´s disease (CD) at least 6 months prior to enrollment were included. This study included 246 patients with IBD (CD: 41%; UC: 59%), with a median age of 39.5 years (IQR 30.7-51.7) for CD and 41.9 years (33.3-55.3) for UC. Overall, 51.5% of CD patients had colonic disease involvement, while 45.5% of UC patients had extensive colitis. At enrollment, the overall use of biologics was high, especially in CD patients (CD: 73.2% vs. UC: 30.3%, p<0.001), while the use of immunosuppressants was similar (∼41%, p=1.000) for both diseases. IBD treatments ever prescribed and healthcare resources utilization during the retrospective period were (CD, UC): biologics: 79.2%, 33.8% (p<0.001); immunosuppressants: 65.3%, 58.6% (p=0.352); aminosalicylates: 62.4%, 97.9% (p<0.001); corticosteroids: 55.4%, 69.7% (p=0.031); surgery: 17.8%, 1.4% (p<0.001); and hospitalizations: 33.7%, 21.4% (p=0.039). In this cohort of IBD patients, overall prescription patterns of conventional therapy were similar to reports elsewhere; however, biologic therapy use was high, especially in CD, consistent with disease behavior and possibly reflecting better access to care in referral centers. Interestingly, over half of CD patients presented colonic involvement.

The role of PD-1/PD-L1 pathway in ulcerative colitis and changes following tonsil-derived mesenchymal stem cells treatment

Background/Aims: The programmed death 1 (PD-1)/programmed death-ligand 1 (PD-L1) pathway has not been fully evaluated in inflammatory bowel disease. We evaluated PD-1/PD-L1 levels in patients with ulcerative colitis (UC) and their significance in tonsil-derived mesenchymal stem cells (TMSCs) treatment.Methods: Using acute and chronic murine colitis model, we measured the PD-1 and PD-L1 levels in inflamed colonic tissues pre- and post-treatment with TMSCs. We also measured PD-1 and PD-L1 levels in colonic tissues from UC patients, compared to normal controls.Results: In the analysis using human colonic tissues, a significant increase in the levels of PD-1 and PD-L1 was observed in the colonic mucosa of patients with UC compared with normal controls (&lt;i&gt;p&lt;/i&gt; &lt; 0.001 and &lt;i&gt;p&lt;/i&gt; = 0.005, respectively). When comparing the maximal disease extent, PD-L1 levels were highest in patients with proctitis (38.5 ± 46.7), followed by left-side colitis (17.5 ± 23.1) and extensive colitis (5.2 ± 8.2) (&lt;i&gt;p&lt;/i&gt; &lt; 0.001). In the chronic colitis model, the level of PD-L1 was decreased (&lt;i&gt;p&lt;/i&gt; = 0.040) and the level of PD-1 increased more than in normal controls (&lt;i&gt;p&lt;/i&gt; = 0.047). After treatment with TMSC, significant improvements were observed in body weight, disease activity index, and colon length recovery. Additionally, the levels of PD-1 and PD-L1 were recovered; PD-L1 significantly increased (&lt;i&gt;p&lt;/i&gt; = 0.031), while the level of PD-1 decreased (&lt;i&gt;p&lt;/i&gt; = 0.310).Conclusions: The altered expression of PD-1 and PD-L1 in colonic mucosa may be a possible mechanism of UC, and T-MSC-derived PD-L1 could help suppress colitis.

Treatment of mildandmoderateforms of ulcerativecolitis: the possibilities of mesalazine

The article indicates the specific niche and principles for choosing mesalazine formulations, and the selection of a dose for the treatment of mild to moderate extensive (left-sided and total) ulcerative colitis (UC). It doesn’t consider any approaches to the treatment of more severe UC or distal UC (proctitis). The current concepts on the use of 5-aminosalicylic acid (5-ASA) formulations to induce and maintain remission in mild to moderate active UC are discussed. The principles for drug administration and a comparative analysis of domestic and international mesalazine dosing recommendations are provided. The guidelines place special emphasis on the importance of high-dose mesalazine therapy (≥4 g/day), which allows to achieve the targets set by the Treat-to-target (T2T) strategy and to reach the clinical and endoscopic remission. The evidence from meta-analyses and comparative studies demonstrating the same efficacy of different forms of mesalazine in the treatment of UC are presented. Attention is drawn to the choice of the optimal drug with enteric coating that consists of two types of Eudragit (Eudragit L and Eudragit S) in contrast to mesalazine formulations with one and the same type of coating (only L or only S). The double Eudragit (L + S) pH-dependent coating of mesalazine tablets dissolves in the terminal ileum, cecum and partially in the right half of the colon at pH 6–7.5, while formulations coated with only L or S dissolve at a narrower pH range. The clinical efficacy of mesalazine directly depends on its intraluminal concentration that is determined by the amount of the released drug according to the pH level in the intestinal lumen. The double Eudragit coating allows to cover the entire pH range in the ileum and colon. The paper presents evidence from the domestic clinical practice that confirms the Cochrane meta-analysis statements on the comparable efficacy of different mesalazine formulations concerning the targets to reach remission and reduce the level of fecal calprotectin. In addition, a high incidence of clinical remissions (more than 80% at 48 weeks of treatment) on double coated (L + S) mesalazine is demonstrated.

A trend analysis of inflammatory bowel disease in non-endemic era (1993-2023)

Aims: In this study, we aimed to evaluate the demographic and epidemiological trends of ulcerative colitis (UC) and Crohn’s disease (CD) in non-endemic era for inflammatory bowel disease (IBD) during the past three decades. Methods: UC and CD patients who had follow-up at least 6 months between June 1993 and February 2023 were evaluated retrospectively. Electronic medical databases, personal queries and IBD registries have all been used to collection data on the clinical and demographic characteristic of all patients. Results: A total of 1549 adult patients with UC and CD were admitted to study. UC was diagnosed in 873 (56.4%) patients (male 538, 61.6%) and CD was diagnosed in 676 (43.6%) patients (male 404, 59.8%). Median total disease duration was 8.3 years in UC group, as well as 6.8 years in CD group. In patients with UC, proctitis was 154 (17.6%), left sided colitis was 410 (47%) and extensive colitis was 309 (35.4%). In CD patients, ileal involvement was found in 297 (43.9%), colonic in 76 (11.2%), ileo-colonic in 299 (44.2%) and isolated upper gastrointestinal involvement in 4 (0.6%) cases. 529 (78.3%) patients had inflammatory disease (non-stenosing non-penetrating behavior), 45 (6.7%) had stenosing behavior, 102 (15.1%) had penetrating behavior, as well as 196 (29%) patients had perianal disease. Mesalazine 658 (75.4%) and thiopurine 397 (45.5%) were the most frequently used conventional treatments for UC, while thiopurine 304 (45%) was most commonly used for CD patients. In the last two-decade, proportion of the biologic usage were 27.9% and 32.1% in UC patients 28.5% and 31.4% in CD patients respectively. Over the three decades, abdominal surgery was 49.2%, 27.8% and 36.3% in CD and colectomy rates was 2.0%, 2.7% and 3.7% in UC patients. While the rate of UC patients has slightly decreased to 98 (61.6%), 401 (58.5%) and 374 (53%) frequency of CD patients has increased to 61 (38.4%), 284 (41.5%) and 331 (47%). Over the course of three decades, there were more UC patients than CD patients, however proportion of UC/CD has been continuously decreased (1.61, 1.41 and 1.13) for three decades respectively. Conclusion: Our study showed that the frequency of UC and CD has significantly increased during the previous three decades in non-endemic era for IBD. While the frequency of UC patients has slightly decreased, that of CD patients has steadily increased over the past three decades. Although the use of biologics has significantly increased, proportions of the major abdominal surgeries and colectomies has not prominently changed.

Fate of ileorectal anastomosis for treating Crohn's disease in the era of biologics: Results from a French retrospective multicentre cohort study.

The rate of surgical recurrence following ileorectal anastomosis (IRA) in patients with Crohn's disease (CD) remains poorly understood. Most studies were conducted before the advent of biologics. Our aim was to assess the fate of IRA in patients with CD during the biologics era and identify risk factors for endoscopic, clinical, and surgical recurrence. This retrospective multicentre cohort study included patients with CD who underwent IRA between 2006 and 2022. The association of patient characteristics and postoperative measures with each type of postoperative recurrence and need for a definitive stoma was investigated using the chi-square test or Fisher's exact test. During a median follow-up period of 60 months, the rates of endoscopic, clinical, and surgical postoperative recurrence were 70%, 59%, and 35%, respectively. The rate of perianal lesions was higher in patients who underwent a definitive stoma (70% vs. 35%, p = 0.007) and with endoscopic (50% vs. 25%, p = 0.038), clinical (54% vs. 24%, p = 0.006), and surgical (63% vs. 34%, p = 0.015) recurrence. The incidence of residual microscopic disease at the rectal margin was higher in patients with endoscopic recurrence (p = 0.047). Biologics were identified as protective factors against the need for a definitive stoma (p = 0.044). IRA is a good treatment option for extensive colitis in patients with CD. However, its consideration should be weighed in the presence of perianal lesions, which have been shown to be a risk factor for delayed proctectomy.

Long-term real-world data of ustekinumab in ulcerative colitis: the Stockholm Ustekinumab Study (STOCUSTE).

Ustekinumab (UST) is an anti-interleukin-12/23 antibody used in the treatment of inflammatory bowel disease. This study includes patients treated at four hospitals in Stockholm to provide long-term real-world data. Retrospective study including patients diagnosed with ulcerative colitis and treated with UST between the years 2019 and 2021. Patients were followed until withdrawal of treatment, or until a predefined end of study, 31 July 2021. Disease activity was assessed with Physician Global Assessment (PGA); Ulcerative Colitis Endoscopic Index of Severity (UCEIS), laboratory parameters, and drug persistence. The primary outcome was steroid-free remission (PGA = 0) and response (decrease PGA ≥ 1 from baseline) at 3 and 12 months, respectively. A total of 96 patients, 44 women and 52 men were included. The patients had either extensive colitis (69%), left-sided colitis (29%), or proctitis (3%). All but two patients were anti-TNF-experienced; 94 (98%) had failed ≥1, 59 (61%) ≥ 2, and 34 (35%) had failed ≥ 3 anti-TNF drugs. In addition, 28 (29%) had failed vedolizumab. At inclusion, 92/96 patients (96%) had active disease and four patients were in remission. Among patients who were treated with UST, 9/71 (13%) were in steroid-free remission at 3 months, and 26/33 (78%) were at 12 months. Withdrawal rates at 3 and 12 months, were 12 and 26%, respectively, mainly due to persisting disease activity (20%). In this group of patients with difficult-to-treat ulcerative colitis, UST was shown to be effective in the majority, with high drug persistence at 12 months in combination with a favorable safety profile.

Differences in disease characteristics and treatment exposures between paediatric and adult-onset inflammatory bowel disease using a registry-based cohort.

Previous studies highlighted a more extensive phenotype for paediatric-onset than adult-onset inflammatory bowel disease (IBD). However, most lacked long-term follow-up, and some were conducted before the era of biologics. The aim of this study is to compare disease characteristics and treatment exposures between paediatric-onset and adult-onset IBD. From a registry that periodically and uniformly retrieves demographics, disease characteristics/phenotype, and treatments, we compared the characteristics of paediatric-onset (diagnosed at ≥6 and <18 years) and adult-onset IBD, diagnosed during 2000-2022 and with ≥12 months follow-up. Of the 2837 patients with Crohn's disease and 1332 with ulcerative colitis, 3316 had adult-onset and 853 paediatric-onset IBD. The median follow-up was 6 years. Patients with paediatric-onset presented with more extensive disease and received more intensified therapies, including biologics and JAK inhibitors than those with adult-onset IBD. Paediatric-onset ulcerative colitis showed a higher prevalence of E3 extensive colitis including pancolitis and a greater requirement for systemic steroids, immunomodulators, and biologics than adult-onset ulcerative colitis. Paediatric-onset versus adult-onset Crohn's disease exhibited greater L3 ileocolonic involvement and perianal disease phenotype, and higher exposure to immunomodulators and biologics. Kaplan-Meier curve and Cox proportional hazards analyses showed significantly lower 15-year biologic-free survival from diagnosis among those with paediatric-onset IBD than with adult-onset IBD (p = <0.001), indicating greater and earlier use of biologics in the former. Paediatric-onset presents with more extensive disease with higher exposures to immunomodulators and biologic therapies than adult-onset IBD.

Endoscopic findings of immune checkpoint inhibitor-related gastrointestinal adverse events.

The use of immune checkpoint inhibitors (ICIs) for the treatment of various malignancies is increasing. Immune-related adverse events can occur after ICI administration, with gastrointestinal adverse events constituting a significant proportion of these events. When ICI-related diarrhea/colitis is suspected, endoscopic evaluation is recommended to differentiate it from other etiologies and assess the severity of colitis. The distribution of intestinal inflammation in ICI-related colitis demonstrates a high frequency of extensive colitis (23-86%). However, isolated right-sided colitis (3-8%) and ileitis (2-16%) are less prevalent. Endoscopic findings vary and predominantly encompass features indicative of inflammatory bowel disease, including aphthae, ulcers, diffuse or patchy erythema, mucosal edema, loss of vascular pattern, and friability. The presence of ulcers and extensive intestinal inflammation are associated with a reduced response to treatment. Microscopic inflammation can be observed even in endoscopically normal mucosa, underscoring the need for biopsies of seemingly normal mucosa. Histological findings present with acute/chronic inflammation and occasionally exhibit characteristics observed in inflammatory bowel disease, microscopic colitis, or ischemic colitis. The first-line therapeutic choice for ICI-related diarrhea/colitis with a common terminology criteria for adverse events grade of 2 or above is corticosteroids, whereas infliximab and vedolizumab are recommended for refractory cases.

Study of Inflammatory Bowel Disease in Patients Undergoing Colonoscopy at a Tertiary Center of Nepal.

Introduction Inflammatory bowel disease (IBD) is a chronic inflammatory condition of thegastrointestinal tract that includes ulcerative colitis (UC) and Crohn's disease (CD). The incidence and prevalence ofdisease are on a rising trend. Increasedcase detection is related tobetterhealth awareness andimprovedavailability of diagnostic services in the community. This articleaims to calculate the incidence of IBD per 1,000 colonoscopies per yearandto study the clinical and demographic characteristics of patients with IBD. Methodology It was a prospective observational study done at the National Academy of Medical Sciences, Bir Hospital, Kathmandu, Nepal, from March 2023 to February 2024.All the patients who underwent colonoscopy during the study period were assessed for possible diagnosis of IBD. TheIncidence rate was calculated as new IBD cases per 1,000 colonoscopies per year. Demographic and clinical profiles of the patients were collected. Results Among 1,248 patients who underwent colonoscopy during the study period, IBD was detected in 52 patients (4.16%). UC was diagnosed in 43 patients and the incidence rate of it was calculated to be 34.4 casesper 1,000 colonoscopies per year. Similarly, CD was diagnosed in nine patients with its incidence rate being 7.2 cases per 1,000 colonoscopies per year. Disease was predominantly seen in females (F:M ratio - 1.36:1). The mean age at diagnosis of IBD was 39.67 ± 14.53 years, with patients with CD being slightly younger than those with UC. The majority of patients with UC had pancolitis. The median time todiagnosis from symptom onset was three years (range: 6 months to 7 years) for CD and 10 months for patients with UC (range: 2 months to 5 years). The most common extra-intestinal manifestations were arthralgia (11, 21.15%) and arthritis (7, 13.46%). Traditional drugs like mesalamine, prednisolone, and azathioprine were commonly prescribed. Biologics were used only in two (3.84%) patients, including infliximab and adalimumab. Janus kinase inhibitor (tofacitinib) was used in three(5.76%) patients in cases of acute severe UC. Conclusions Due to the rising trend of awareness in health and availability of colonoscopyservices in our country like Nepal, the incidence of IBD is seen to be quite high. UC was seen more commonly than CD, and females were predominantly involved. The majority of patients belonged to the young and middle-aged population.The majority of patients with UC had extensive colitis, while patients with CD had ileo-colonic disease with non-stricturing, non-penetrating phenotypes. Arthralgia and arthritis were the most common extra-intestinal manifestations. Conventional drugs like mesalamine, prednisolone, and immunomodulators such as azathioprine were mostly used. The use of biologics was fairly low. This study certainly contributes to the existing literature from Nepal regarding IBD.

Extensive Colitis and Smoking Are Associated With Postoperative Complications Within 30 Days of Ileal Pouch-Anal Anastomosis.

Our understanding of outcomes after proctocolectomy with ileal pouch-anal anastomosis (IPAA) for ulcerative colitis (UC) is largely based on analyses of selected populations. We created a state-level registry to evaluate the epidemiology of IPAA surgery and pouch-related outcomes across the major healthcare systems performing these surgeries in our state. We created a retrospective cohort of all patients undergoing restorative proctocolectomy with IPAA for UC at 1 of 4 centers between January 1, 2018, and December 31, 2020. The primary outcomes of this study were the rate of complications and all-cause readmissions within the first 30 days of the final stage of IPAA surgery. During the study period, 177 patients underwent IPAA surgery with 66 (37%) experiencing a complication within 30 days. After adjusting for the number of stages in IPAA surgery, patients with extensive UC (odds ratio, 3.61; 95% confidence interval, 1.39-9.33) and current or former smokers (odds ratio, 2.98; 95% confidence interval, 1.38-6.45) were more likely to experience a complication. Among all patients, 57 (32%) required readmission within 30 days. The most common reasons for readmission were ileus/small bowel obstruction (22%), peripouch abscess (19%), and dehydration (16%). In this first state-level examination of the epidemiology of IPAA for UC, we demonstrated that the complication rate after IPAA for UC was 37%, with one-third of patients being readmitted within 30 days. Extensive disease at the time of colectomy appears to be an indicator of more severe disease and may portend a worse prognosis after IPAA.

Chronic myeloid leukemia in an ulcerative colitis patient receiving azathioprine: A case report.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease usually treated by azathioprine. It is a well-established risk factor for colorectal cancers and extraintestinal malignancies. Nevertheless, the risk of myeloid leukemia in patients with UC is less known. We report a case of a 51-year-old patient, with a history of extensive ulcerative colitis, who was treated with azathioprine at a dose of 2.5 mg/kg/day. Seven years later, he presented an increased count of white blood cells at 25,400/μL and of platelets at 1,382,000/μL. Peripheral blood smear showed 1% blasts and 20% myelemia. The karyotype showed the Philadelphia chromosome and the RT-PCR revealed the BCR-ABL transcript. Thus, chronic myeloid leukemia (CML) was confirmed and imatinib was prescribed. This case reported a rare and serious event in a UC patient and illustrates the importance of closely monitoring this population.

Natural course of ulcerative colitis in China: Differences from the West?

Whether the natural course of ulcerative colitis (UC) in mainland China is similar or different from that in Western countries is unknown, and data on it is limited. We aimed to provide a comprehensive description of the natural course of UC in China and compare it with Western UC patients. Based on a prospective Chinese nationwide registry of consecutive patients with inflammatory bowel diseases, the medical treatments and natural history of UC were described in detail, including disease extension, surgery, and neoplasia. The Cox regression model was used to identify factors associated with poor outcomes. A total of 1081 UC patients were included with a median follow-up duration of 5.3years. The overall cumulative exposure was 99.1% to 5-aminosalicylic acids, 52.1% to corticosteroids, 25.6% to immunomodulators, and 15.4% to biologics. Disease extent at diagnosis was proctitis in 26.9%, left-sided colitis in 34.8%, and extensive colitis in 38.3%. Of 667 patients with proctitis and left-sided colitis, 380 (57.0%) experienced disease extent progression. A total of 58 (5.4%) UC patients underwent colectomy, demonstrating cumulative proportions of surgery at 1, 5, and 10years after diagnosis of 0.6%, 3.4%, and 8.2%, respectively. In addition, 23 (2.1%) UC patients were diagnosed with neoplasia, demonstrating cumulative proportions of neoplasia at 1, 5, and 10years after diagnosis of 0.5%, 1.0%, and 3.5%, respectively. Chinese UC patients had similar cumulative proportions of exposure to IBD-specific treatments but a lower surgical rate than patients in Western countries, indicating a different natural course, and close monitoring needs for UC in China. However, these results must be confirmed in population-based studies because the hospital-based cohort in our study might lead to selection bias.

Need for therapeutic escalation in patients with refractory ulcerative proctitis: Results from the PROCU study of the ENEIDA registry.

Ulcerative proctitis (UP) can have a milder, less aggressive course than left-sided colitis or extensive colitis. Therefore, immunosuppressants tend to be used less in patients with this condition. Evidence, however, is scarce because these patients are excluded from randomised controlled clinical trials. Our aim was to describe the characteristics of patients with refractory UP and their disease-related complications, and to identify the need for immunosuppressive therapies. We identified patients with UP from the prospective ENEIDA registry sponsored by the GETECCU. We evaluated socio-demographic data and complications associated with immunosuppression. We defined immunosuppression as the use of immunomodulators, biologics and/or small molecules. We used logistic regression to identify factors associated with immunosuppressive therapy. From a total of 34,716 patients with ulcerative colitis, we identified 6281 (18.1%) with UP; mean ± SD age 53 ± 15 years, average disease duration of 12 ± 9 years. Immunosuppression was prescribed in 11% of patients, 4.2% needed one biologic agent and 1% needed two; 2% of patients required hospitalisation, and 0.5% underwent panproctocolectomy or subtotal colectomy. We identified 0.2% colorectal tumours and 5% extracolonic tumours. Patients with polyarthritis (OR 3.56, 95% CI 1.86-6.69; p < 0.001) required immunosuppressants. Among patients with refractory UP, 11% required immunosuppressant therapy, and 4.2% required at least one biologic agent.

Faecal volatile organic compounds differ according to inflammatory bowel disease sub-type, severity, and response to treatment in paediatric patients.

Faecal volatile organic compounds (VOCs) differ with disease sub-type and activity in adults with established inflammatory bowel disease (IBD) taking therapy. To describe patterns of faecal VOCs in children newly presented with IBD according to disease sub-type, severity, and response to treatment. Children presenting with suspected IBD were recruited from three UK hospitals. Children in whom IBD was diagnosed were matched with a non-IBD child for age, sex, and recruitment site. Faecal VOCs were characterised by gas chromatography-mass spectrometry at presentation and 3months later in children with IBD. In 132 case/control pairs, median (inter-quartile range) age in IBD was 13.3years (10.2-14.7) and 38.6% were female. Compared with controls, the mean abundance of 27/62 (43.6%) faecal VOCs was statistically significantly decreased in Crohn's disease (CD), ulcerative colitis (UC) or both especially amongst ketones/diketones, fatty acids, and alcohols (p<0.05). Short-chain, medium chain, and branched chain fatty acids were markedly reduced in severe colitis (p<0.05). Despite clinical improvement in many children with IBD, the number and abundance of almost all VOCs did not increase following treatment, suggesting persistent dysbiosis. Oct-1-en-3-ol was increased in CD (p=0.001) and UC (p=0.012) compared with controls and decreased following treatment in UC (p=0.01). In CD, propan-1-ol was significantly greater than controls (p<0.001) and extensive colitis (p=0.001) and fell with treatment (p=0.05). Phenol was significantly greater in CD (p<0.001) and fell with treatment in both CD (p=0.02) and UC (p=0.01). Characterisation of faecal VOCs in an inception cohort of children with IBD reveals patterns associated with diagnosis, disease activity, and extent. Further work should investigate the relationship between VOCs and the microbiome in IBD and their role in diagnosis and disease monitoring.

Clinical course of ulcerative colitis: Frequent use of biologics and low colectomy rate first year after diagnosis-results from the IBSEN III inception cohort.

The introduction of biologic therapies and the 'treat-to-target' treatment strategy may have changed the disease course of ulcerative colitis (UC). To describe the early disease course and disease outcome at 1-year follow-up in a population-based inception cohort of adult patients with newly diagnosed UC. The Inflammatory Bowel Disease in South-Eastern Norway (IBSEN) III study is a population-based inception cohort study with prospective follow-up. Patients newly diagnosed with inflammatory bowel disease during 2017-2019 were included. Patients ≥18 years at diagnosis of UC who attended the 1-year follow-up were investigated. We registered clinical, endoscopic and demographic data at diagnosis and 1-year follow-up. We included 877 patients with UC (median age 36 years (range: 18-84), 45.8% female). At diagnosis, 39.2% presented with proctitis, 24.7% left-sided colitis and 36.0% extensive colitis. At the 1-year follow-up, 13.9% experienced disease progression, and 14.5% had received one or more biologic therapies. The colectomy rate was 0.9%. Steroid-free clinical remission was observed in 76.6%, and steroid-free endoscopic remission in 68.7%. Anaemia and initiation of systemic steroid treatment at diagnosis were associated with biologic therapy within the first year after diagnosis. In this population-based inception cohort, colectomy rate in the first year after diagnosis was low, and a high proportion of patients were in remission at 1-year follow-up. The use of biologic therapy increases, consistent with findings from previous studies.

Proportion of inflammatory bowel diseases patients withsuboptimal disease control in daily clinical practice-Real-world evidence from the inflammatory bowel diseases-podcast study.

Crohn's disease and ulcerative colitis (UC) are inflammatory bowel diseases (IBD) characterized by a progressive nature of the disease resulting in subsequent intestinal damage, limited efficacy of current treatments and suboptimal disease management and a significant burden for patients. The IBD-PODCAST study aims to estimate the proportion of Crohn's disease and UC patients with suboptimal disease control (SDC) in a real-world setting. A non-interventional and cross-sectional study was conducted across 103 sites in 10 countries (Austria, Belgium, Canada, Germany, Greece, Italy, Portugal, Spain, Turkey, and UK). Criteria for SDC were based on STRIDE-II criteria and adapted by an expert panel. 2185 patients (Crohn's disease: n=1,108, UC: n=1077) with a mean (SD) age of 44.0 (14.8) years and mean (SD) disease duration of 12.4 (9.2) years were included (52.2% male). Ileal involvement was present in 39.1% of Crohn's disease patients, 35.3% of UC patients had extensive colitis. 77.3% of Crohn's disease and 65.3% of UC patients were on targeted immunomodulators and, according to STRIDE-II-based treatment phases, 85.6% of Crohn's disease and 85.4% of UC patients were assigned to the long-term treatment phase. SDC was detected in 52.2% of Crohn's disease and 44.3% of UC patients predominantly due to impaired quality of life (QoL), clinically significant extraintestinal manifestations, steroid overuse, signs of active inflammation in UC and Crohn's disease, and active fistulas in Crohn's disease. More than one criterion was seen in 37% of patients with SDC. Opportunities for on-label treatment optimization were observed in 49% of Crohn's disease and 61% of UC patients on advanced therapy. The high percentage of SDC in this global, real-world cohort suggests a large disease burden and high unmet medical need in IBD patients. Future analysis should focus on monitoring and responding to SDC in this cohort and on patients' QoL.

Differential efficacy of medical therapies for ulcerative colitis according to disease extent: patient-level analysis from multiple randomized controlled trials

Disease extent in Ulcerative Colitis (UC) has prognostic implications for disease course. It is unclear whether the efficacy of medical therapies for moderate to severely active UC vary according to disease extent at enrollment. We analyzed patient level data from 11 Phase 2 and 3 clinical trials of advanced therapies in patients with moderate-to-severe UC to assess modifications of advanced therapy effects by disease extent. Primary outcome was clinical response and secondary outcomes were clinical remission, endoscopic response/remission and endoscopic improvement, and Mayo clinic subscore for both induction and maintenance studies. Binary and continuous outcomes were analyzed using the modified Poisson regression model and the mixed-effects model, respectively, adjusting for age, sex, disease duration, concomitant steroid use and prior anti-TNF use. Effect modifications with binary outcomes were quantified by ratios of risk ratio for left-sided to that for extensive colitis while effect modifications with the Mayo subscores were quantified by differences of the differences between mean scores of the left-sided and extensive colitis. Results were presented with point estimates and 95% confidence intervals as well as p-values. Eleven clinical trials enrolling 5450 UC patients (infliximab=2, adalimumab=2, golimumab=2, vedolizumab=2, tofacitinib=3) were included. In induction trials, there was evidence to suggest effect modification by disease extent for clinical response with tofacitinib (the ratio of RRs 0.67, 95% CI [0.45, 0.99], p=0.049) and clinical remission with infliximab (ratio of RRs 0.33, 95% CI [0.13, 0.85], p=0.020) favoring patients with extensive colitis. There was no evidence to suggest effect modification for endoscopic improvement and clinical outcomes. There was evidence to suggest effect modification by disease extent for clinical remission with tofacitinib (ratio of RRs 0.44, 95% CI [0.22, 0.89], p=0.020) favoring patients with extensive colitis. For symptom subscores from the Mayo Clinic score, tofacitinib was associated with a greater reduction in both stool frequency (difference of differences 0.37, 95% CI [0.08, 0.65], p=0.012) and rectal bleeding scores (difference of differences 0.25, 95% CI [0.03, 0.47], p=0.026) in patients with extensive colitis compared to left sided. These findings underscore the possibility of differential efficacy of medical therapies according to disease distribution. These results warrant further exploration in forthcoming trials to better inform treatment strategies and consideration of disease distribution as a baseline stratification factor in clinical trials. This study did not receive any financial support.

Colorectal Cancer in Inflammatory Bowel Disease: A Review of the Role of Gut Microbiota and Bacterial Biofilms in Disease Pathogenesis.

The risk of colorectal cancer [CRC] is increased in patients with inflammatory bowel disease [IBD], particularly in extensive ulcerative colitis [UC] and Crohn's colitis. Gut microbiota have been implicated in the pathogenesis of CRC via multiple mechanisms, including the release of reactive oxygen species and genotoxins, and induction of inflammation, as well as activation of the immune response. Gut microbiota can enhance their carcinogenic and proinflammatory properties by organising into biofilms, potentially making them more resistant to the host's immune system and to antibiotics. Colonic biofilms have the capacity to invade colonic tissue and accelerate tumorigenesis in tumour-prone models of mice. In the context of IBD, the prevalence of biofilms has been estimated to be up to 95%. Although the relationship between chronic inflammation and molecular mediators that contribute to IBD-associated CRC is well established, the role of gut microbiota and biofilms in this sequence is not fully understood. Because CRC can still arise in the absence of histological inflammation, there is a growing interest in identifying chemopreventive agents against IBD-associated CRC. Commonly used in the treatment of UC, 5-aminosalicylates have antimicrobial and anticarcinogenic properties that might have a role in the chemoprevention of CRC via the inhibition or modulation of carcinogenic gut microbiota and potentially of biofilm formation. Whether biologics and other IBD-targeted therapies can decrease the progression towards dysplasia and CRC, via mechanisms independent of inflammation, is still unknown. Further research is warranted to identify potential new microbial targets in therapy for chemoprevention of dysplasia and CRC in IBD.

Efficacy and Safety of Etrasimod in Patients with Moderately to Severely Active Isolated Proctitis: Results From the Phase 3 ELEVATE UC Clinical Programme.

Pivotal trials in ulcerative colitis have historically excluded patients with isolated proctitis. Etrasimod is an oral, once-daily, selective sphingosine 1-phosphate1,4,5 receptor modulator for the treatment of moderately to severely active ulcerative colitis. This post hoc analysis assessed efficacy and safety of etrasimod 2 mg once daily in patients with isolated proctitis (centrally read) from the phase 3 ELEVATE UC 52 and ELEVATE UC 12 trials. Patients, including those with isolated proctitis (<10 cm rectal involvement) who met all other inclusion criteria in ELEVATE UC 52 and ELEVATE UC 12, were randomised 2:1 to receive etrasimod or placebo. Primary, secondary and other identified efficacy endpoints and safety were assessed. We analysed data from 64 and 723 patients at Week 12 (both trials pooled), and 36 and 397 patients at Week 52 (ELEVATE UC 52 only) with isolated proctitis and more extensive colitis (≥10 cm rectal involvement), respectively. Patients with isolated proctitis receiving etrasimod demonstrated significant improvements versus placebo, including clinical remission rates at Weeks 12 (42.9% vs 13.6%) and 52 (44.4% vs 11.1%), endoscopic improvement (52.4% vs 22.7%) at Week 12 and bowel urgency numerical rating scale score at Week 12 (all p < 0.01). Generally similar trends were observed in patients with more extensive colitis. Safety was consistent across subgroups, with no new findings. Etrasimod demonstrated significant improvements versus placebo in patients with isolated proctitis, and those with more extensive disease, in most efficacy endpoints at Week 12 and 52. Clinicaltrials.gov: NCT03945188; NCT03996369.

Effectiveness and Safety of Ustekinumab for Ulcerative Colitis: A Brazilian Multicentric Observational Study

Abstract Background and Aims Real-world data on the effectiveness and safety of ustekinumab (UST) in ulcerative colitis (UC) are lacking in Latin America. In this study, we aimed to describe the effectiveness and safety of UST in a real-world multicenter cohort of Brazilian patients with UC. Methods We conducted a multicenter retrospective observational cohort study, including patients with moderate to severe UC (Total Mayo score 6-12, with an endoscopic subscore of 2 or 3) who received UST. The co-primary endpoints were clinical remission, defined as a total Mayo score ≤2 at 1 year, with a combined rectal bleeding and stool frequency subscore of ≤1, and endoscopic remission (endoscopic Mayo subscore of zero) within one year from baseline. Secondary endpoints included clinical response between weeks 12-16, endoscopic response within one year of starting UST, steroid-free clinical remission at week 52, and biochemical remission at week 52. We also evaluated UST treatment persistence and safety. Results A total of 50 patients were included (female, n=36, 72.0%), with a median disease duration of 9.2 years (1-27). Most patients had extensive colitis (n=38, 76.0%), and 43 (86.0%) were steroid-dependent at baseline. Forty patients (80.0%) were previously exposed to biologics (anti-TNF drugs, n=31; vedolizumab [VDZ], n=27). The co-primary endpoints of clinical remission at 1 year and endoscopic remission within 1 year were achieved by 50.0% and 36.0% of patients, respectively. Clinical response at weeks 12-16 was 56.0%, endoscopic response, steroid-free clinical remission, and biochemical remission at week 52 were 68.0%, 46.5%, and 50.0%, respectively. The UST treatment persistence rate at 24 months was 73.7%. During the follow-up, 10 patients (20.0%) were hospitalized, mostly due to disease progression, and three patients required colectomy. Nine patients (18.0%) discontinued the drug mainly due to a lack of effectiveness. Twenty-seven adverse events (AEs) were reported, 16 of which were considered as serious AEs. Conclusion In this real-world cohort of difficult-to-treat UC patients, UST was associated with improvements in clinical, biochemical, and endoscopic outcomes. The safety profile was favorable, consistent with the known profile of UST.