Severe Ulcerative Colitis Research Articles

Predictors for colectomy in patients with acute severe ulcerative colitis: a systematic review and meta-analysis

ObjectivesAcute severe ulcerative colitis (ASUC) poses challenges to patient management owing to its high surgical rate. This study aimed to identify predictors of colectomy in patients with ASUC.DesignThis is a...

Effectiveness of Ustekinumab for patients with moderate to severe Ulcerative Colitis: A Multi-Center Real-World Canadian Study

Background: We aimed to evaluate the real-world effectiveness and safety of ustekinumab for the treatment of both bio-naïve and bio-exposed ulcerative colitis (UC) patients in a real-world setting. Methods: Retrospective, Canadian multicenter cohort study. Primary outcomes were clinical remission and endoscopic remission. Key secondary outcomes included composite clinical and endoscopic response, safety, and persistence. Univariable logistic regression was conducted to examine associations between baseline factors and 12 month clinical and endoscopic response and remission. The primary focus was on the association between these outcomes and bio-exposure status. Results: A total of 198 patients were included, of whom 47.5% were female and 85.9% under 65 years. The majority had severe endoscopic activity at baseline (47.5%, n=87) and were bio-exposed (88.8%, n=176; 33%, n=66 prior failure of 3 or more biologics). Patients were followed for a median of 12.8 (IQR 8.2 to 22.1) months after induction. The overall clinical remission rates were 41.3% (69/167), 38.1% (56/147), and 43.6% (58/133) at 3, 6 and 12 months, respectively. Endoscopic remission rates (MES=0) were 8.0% (7/88), 18.7% (23/123), and 12.5% (11/88) at 3, 6, and 12 months, respectively, and consistently higher in bio-naïve patients compared to bio-exposed patients through 12 months (p<0.05 at all time points). Bio-naive patients were more likely to achieve endoscopic remission compared to bio-exposed (HR=5.40, 95% CI: 1.08-26.93). Adverse events were reported in 14.1% (18/198). Discussion: In a highly refractory and largely bio-exposed population, a substantial proportion of patients with UC treated with ustekinumab can achieve clinical and endoscopic outcomes of importance after 12 months. Prior biologic exposure is associated with lower rates of endoscopic remission.

Metabolic stress in patients with acute severe ulcerative colitis - a single-center cohort study

Background and aimsAcute severe ulcerative colitis (ASUC) is characterized by systemic inflammation, which may initiate an acute-phase response leading to hypercatabolism. Patients with ASUC are usually treated with high-dose steroids that may further accelerate the metabolic response and lead to hyperglycemia and insulin resistance. Nevertheless, the degree of synergy between inflammation and steroid treatment and their influence on the insulin resistance remains unknown. We aimed to measure the degree of metabolic stress including insulin resistance in patients with ASUC during admission and three weeks after discharge.MethodsThis single-center cohort study was conducted in adult patients with ASUC, defined and assessed by Truelove and Witt’s criteria. Indirect calorimetry, bioelectrical impedance analysis, and the Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) were applied at baseline and at follow-up three weeks after discharge.ResultsAmong the 22 patients admitted during the project period, 15 provided consent for participation in the study. Median C-reactive protein at inclusion was 37.6 [4; 154.7]. Both median HOMA-IR and fasting plasma glucose were markedly increased at inclusion (median 8.6 [3.8; 14.1] and 7.1 [6; 8.7], respectively), and both had decreased significantly three weeks after discharge (p=0.0036 and p=0.0039, respectively). No significant differences were observed in resting energy expenditure or anthropometric measurements from baseline to follow-up.ConclusionPatients with ASUC presented with marked insulin resistance, indicating that the days following admission and high-dose steroid treatment are particularly vulnerable. Despite improvement at three-week follow-up, patients still exhibited insulin resistance compared with relevant control groups.Clinical trial registrationClinicalTrials.gov, identifier NCT0527183.

Efficacy of Janus Kinase Inhibitors (JAKi) in the treatment of biologic-naive and biologic-experienced patients with ulcerative colitis

Abstract Introduction Janus kinase inhibitors (JAKi) are an orally available treatment for patients with moderately to severe ulcerative colitis (UC). There are currently 3 JAKi for UC: tofacitinib, filgotinib and upadacitinib with variable selectivity to JAK-11. There is limited data comparing the outcomes between biologic-naive and biologic-experienced patients. This study describes the effectiveness of JAKi according to biologic exposure. Aim To investigate the effectiveness of 3 the JAKi’s, tofacitinib, filgotinib and upadacitinib according to biologic exposure. Method We undertook a retrospective study of UC patients treated with JAKi within a tertiary hospital. Clinical endpoints were assessed at week 8-12. Baseline disease activity, previous advanced therapies and use of corticosteroids were documented. Clinical response was defined as reduction in SCCAI score by ≥3 points from baseline or a sustained score of <2.5. Clinical remission was defined as a SCCAI score of < 2.5, and/ or a calprotectin level of <250 mg/g with a CRP of < 5mg/L. Ethical approval has been granted by HRA and Health and Care Research Wales (HCRW) (REC ref: 24/HRA/1198) Results 52 patients were reviewed at week 8-12 following their first dose. 15, 15 and 22 patients were on tofacitinib, filgotinib, and upadacitinib respectively. 3 (20%) of patient in the tofacitinib group were exposed to at least 3 biologics prior to initiating the JAK Inhibitor, followed by upadacitinib which was 3 (14%) of patients. In the tofacitinib group, most patients were exposed to 2 previous biologics (n=7, 47%), whereas majority of patients on filgotinib and upadacitinib had exposure to 1 previous biologic, 7 (47%) and 8 (36%) patients respectively. For the patient group exposed to 3 or more biologics (n=7, 14%), 100% patients on tofacitinib (n=3) and upadacitinib (n=3) achieved clinical remission by week 8-12, whereas none of the patients on filgotinib achieve clinical remission. In biologic naïve patients, filgotinib demonstrated the greatest improvement in calprotectin score with a reduction in 30% from baseline (n=2, 100%). In patients exposed to ≥3 biologics, upadacitinib achieved higher rates of improvement in faecal calprotectin score (n=2, 100%). Conclusion Our observations suggest that patients exposed to at least 3 biologics, tofacitinib and upadacitinib were the most effective, whereas filgotinib seems to be more effective in biologic naïve patients. Our patient cohort is small. We will continue to collect data and undertake further statistical analysis to examine the significance of the observations and factors associated with effectiveness. Reference 1. Goetsch, A et al. Advances in pharmacotherapy for ulcerative colitis: a focus on JAK1 inhibitors. Expert Opinion on Pharmacotherapy, 2023, 24(7), 849–861.

Extended Monitoring for Transition to Oral Corticosteroids in Acute Severe Ulcerative Colitis May Be Unnecessarily Prolonging Length of Stay.

There is no guideline regarding whether patients treated with intravenous corticosteroids for acute severe ulcerative colitis (ASUC) should be monitored in the hospital after transitioning to oral steroids. Our study aimed to: (1) compare rates of oral steroid transition failure and 30-day readmission between ASUC hospitalizations with extended inpatient monitoring compared to accelerated inpatient monitoring, and (2) identify predictors of oral steroid transition failure. A retrospective cohort study of ulcerative colitis (UC) related admissions at UCSF from 2014 to 2022 was conducted comparing rates of steroid transition failures in extended inpatient monitoring (≥ 24h on oral steroids prior to discharge) to accelerated inpatient monitoring (< 24h on oral steroids). Steroid transition failure was defined as worsening colitis activity with the need to return to IV steroids or undergo colectomy. Data analysis incorporated demographics, disease features, and treatment history. Transition failures from intravenous to oral corticosteroids occurred in 8% of all UC-related admissions. There was a significant difference in transition failure observed between the extended and accelerated monitoring groups, 13 vs 3% (p = 0.03), respectively, with 83.3% of total transition failures occurring within the extended monitoring group. The 30-day readmission rate was 6% in each group (p = 0.93). No significant predictors of transition failures were identified. Transition failures from IV to oral steroids are uncommon in ASUC hospitalizations. Transition failures were more likely to occur with extended monitoring, suggesting potential predictors and/or patient selection bias within this group. Further studies are needed to investigate the parameters driving clinician decision-making regarding oral steroid transitioning.

Efficacy of Second-Line Biological Therapies in Moderate to Severe Ulcerative Colitis Patients with Prior Failure of Anti-Tumor Necrosis Factor Therapy: A Multi-Center Study.

Few studies have compared the efficacy and safety of second-line biological therapies in ulcerative colitis (UC) patients with prior exposure to anti-tumor necrosis factor (TNF) therapy. We aim to compare the efficacy and safety between ustekinumab, vedolizumab, and tofacitinib, a current option as second-line biological therapy with different mechanisms in those patients. This retrospective multi-center study was conducted across five institutions from 2011 to 2022. We enrolled patients with moderate to severe UC who failed anti-TNF therapy and subsequently received ustekinumab, vedolizumab, or tofacitinib as second-line biological therapy. The outcomes were analyzed for clinical response/remission and endoscopic improvement/remission rates after induction therapy, drug persistency, and adverse events. A total of 70 UC patients were included and grouped into ustekinumab (11 patients), vedolizumab (40 patients), and tofacitinib (19 patients) treatments. The clinical response/remission rates after induction therapy were similar between ustekinumab (90.9/81.8%), vedolizumab (92.5/65.0%), and tofacitinib (94.7/73.7%). There were no significant differences in the endoscopic improvement/remission rates between the three groups: 90.9/18.2% for ustekinumab, 72.5/12.5% for vedolizumab, and 84.2/26.3% for tofacitinib. Drug persistence was similar across the three agents (p = 0.130). Three patients of the tofacitinib group experienced adverse events (herpes zoster and hypertriglyceridemia). Based on real-world data, second-line biological therapy with ustekinumab, vedolizumab, and tofacitinib showed comparable efficacy in patients with moderate to severe UC with prior exposure to anti-TNF therapy.

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.

HLA-DRB1*01:03 and Severe Ulcerative Colitis

This Danish nationwide genome-wide association study aims to identify biomarkers of severe vs less severe ulcerative colitis.

Association between serum vitamin D, uric acid, C-reactive protein, and disease severity in ulcerative colitis: A retrospective study.

Ulcerative colitis (UC) is an inflammatory disease of the intestinal mucosa, and immunodeficiency is the main cause. Vitamin D (VD) has been shown to regulate many immune diseases, and studies have found that the level of uric acid (UA) and C-reactive protein (CRP) may also affect the severity of UC. This study aimed to investigate the correlation between VD levels and disease severity in UC patients. To determine serum VD levels in patients with UC of different ages and genders in China, and to study its correlation with UC, and to analyze its correlation with serum UA levels and CRP, so as to provide guidance for the prevention, diagnosis, and treatment of UC. One hundred three UC patients (64 males and 39 females, aged 16-75 years) were diagnosed with varying severity (mild, moderate, and severe). Serum VD levels, UA levels, and CRP levels were measured by electrochemiluminescence. The serum VD level of patients with severe UC was significantly lower than that of patients with mild UC. Gender was significantly correlated with serum UA, CRP, and disease severity in UC patients. Serum VD levels may affect the disease severity of UC patients, and patients with low serum VD content may have more severe disease. Gender affects serum UA, CRP, and disease severity. Males have significantly higher serum UA and CRP levels than females, while disease severity is generally lower than that of females. However, the mechanism of abnormal serum vitamin and trace element levels in UC patients remains to be further studied.

Predicting Outcomes in Hospitalized Patients With Acute Severe Ulcerative Colitis in a Prospective Multicenter Cohort.

Acute severe ulcerative colitis (UC) (ASUC) requiring hospitalization affects up to 1 in 4 patients with UC. There is a paucity of prospective and multicenter clinical cohorts to study treatment trends and predictors of disease outcomes. Here, we conduct a US-based multicenter prospective clinical cohort of ASUC to study predictors of the need for medical rescue therapy and colectomy. A total of 94 patients hospitalized for ASUC were included across 5 academic centers from December 2018 to December 2021. Demographic, clinical, and laboratory data were collected throughout the hospitalization. Patients were followed up to 1-year post-hospitalization to identify predictors of the need for rescue therapy and colectomy. A total of 21 (22.3%) patients required colectomy within 1 year of admission with 11 (12%) requiring colectomy during the index admission. On multivariate analyses, a BMI < 21.5kg/m2 (OR = 6.16, P = .02), a simple clinical colitis activity index (SCCAI) greater than 8 (OR = 14.44, P = .01) and an albumin level at admission lower than 2.4g/dL (OR = 10.61, P = .04) were significant predictors of inpatient colectomy after adjusting for sex, age, and duration of disease. In a prospective, multicenter cohort of patients hospitalized with ASUC, BMI, SCCAI, and albumin at admission were important determinants of colectomy risk during the index hospitalization and within 1 year of admission. Colectomy rates remain high-22.3% in this cohort across 5 academic, tertiary care centers-underscoring the need to identify the highest-risk patients, establish novel treatment and care paradigms, and examine opportunities to standardize care.

Prognostic Value of CRP/25 OH Vitamin D Ratio for Glucocorticoid Efficacy in Acute Severe Ulcerative Colitis Patients.

Introduction: Acute severe ulcerative colitis (ASUC) represents a life-threatening medical emergency. One-third of ASUC patients are steroid non-responders. Our study aimed to create a new ASUC algorithm to predict corticosteroid response in the early course of the disease. Materials and Methods: A cross-sectional study included 103 patients with ASUC (65 male, 38 female). We calculated the serum CRP to 25-hydroxy 25 OH vitamin D ratio at admission. Logistic regression determined patients' response to glucocorticoids, depending on the CRP/25 OH vitamin D ratio value. Results and Discussion: Significant differences were observed in the CRP/25 OH vitamin D ratio at admission between glucocorticoid responders and non-responders (p = 0.001). A negative correlation was found between glucocorticoid response and CRP/25 OH vitamin D levels (Spearman's rho = -0.338, p < 0.01). Logistic regression revealed a significant association (p = 0.003) with a model chi-square value of 11.131 (p = 0.001). ROC curve analysis showed an AUC of 0.696 (p = 0.001), indicating moderate discriminatory ability. To achieve 91% sensitivity, the CRP/25 OH vitamin D ratio must be less than 3.985 to predict a complete glucocorticoid response. Conclusions: The serum CRP to 25 OH vitamin D ratio on the first day of hospital admission can potentially determine the response to glucocorticoids in patients with ASUC and significantly affect the mortality of these patients.

Real world evidence on the effectiveness and safety of tofacitinib in ulcerative colitis in Lebanon

ObjectiveTo evaluate the effectiveness and safety of tofacitinib in patients with ulcerative colitis (UC) in clinical practice in Lebanon.DesignThis was a retrospective cross-sectional study. The data were collected from hospital records. Patients with moderate to severe UC treated with tofacitinib between 2018 and 2021 were included. Patients’ demographics, disease-specific characteristics, clinical assessment at three time points (8, 26, and 52 weeks), endoscopic evaluation at 24 weeks, and adverse events were collected.ResultsA total of 60 UC patients with a mean duration of disease of 7.9 ± 4.7 years were enrolled. 61.7% of patients had extensive disease, and 58.3% had received ≥ 1 biologic prior to tofacitinib. Clinical remission was reported in 25, 34, and 31 patients (41.7%, 56.7%, and 56.4%) at 8, 26, and 52 weeks respectively. Endoscopic remission (endoscopic Mayo score 0 or 1) was observed in 58.3% of patients at 52 weeks. About one-third of patients (31.7%) stopped tofacitinib at one year, primarily for lack of efficacy or loss of response, with no significant difference between biologics-naïve and experienced patients (24% vs. 37.1% respectively). No serious adverse events or deaths were reported. Adverse events were reported in 3 patients (5.0%) - one C. difficile infection, one case of reversible lymphopenia, and one case of facial acne. No serious adverse events or deaths were noted. On multivariate analysis, biologic-naïve status and reduction or normalization of CRP were associated with clinical remission (OR = 10.87, 95% CI = 1.57, 100, and OR = 78.47, 95% CI = 2.09, 2940.32 respectively), while reduction or normalization of CRP was associated with endoscopic remission at 1 year (OR = 19.03, 95% CI = 1.64, 221.09).ConclusionTofacitinib was effective in the treatment of moderately severe ulcerative colitis in this real-world cohort in Lebanon. Further, the predictors associated with clinical and endoscopic remissions were found to be biologic-naïve status and reduction in CRP. Observed AEs were consistent with the known safety profile. One of the major limitations of this study is the smaller sample size and the retrospective nature of the study.

S1332 Characteristics and Outcomes of Patients Hospitalized With Severe Ulcerative Colitis: A Large Population-Based Cohort Study in the United States

S1332 Characteristics and Outcomes of Patients Hospitalized With Severe Ulcerative Colitis: A Large Population-Based Cohort Study in the United States

S1147 Prophylaxis for Venous Thromboembolism Remains Low in Patients Admitted With Severe UC in the Community Setting

S1147 Prophylaxis for Venous Thromboembolism Remains Low in Patients Admitted With Severe UC in the Community Setting

S1173 Efficacy and Safety of Interleukin-12, 23 Inhibitors vs Interleukin-23 inhibitors for Moderate to Severe Ulcerative Colitis: A Systematic Review and Network Meta-Analysis

S1173 Efficacy and Safety of Interleukin-12, 23 Inhibitors vs Interleukin-23 inhibitors for Moderate to Severe Ulcerative Colitis: A Systematic Review and Network Meta-Analysis

S1387 Real World Efficacy and Safety Outcomes Analysis of Upadacitinib in Acute Severe Ulcerative Colitis: A Propensity Score Matched Comparative Effectiveness Study Assessing Infliximab &amp; Upadacitinib

S1387 Real World Efficacy and Safety Outcomes Analysis of Upadacitinib in Acute Severe Ulcerative Colitis: A Propensity Score Matched Comparative Effectiveness Study Assessing Infliximab &amp; Upadacitinib

S3850 Acute severe ulcerative colitis with major acute gastrointestinal hemorrhage

S3850 Acute severe ulcerative colitis with major acute gastrointestinal hemorrhage

S1149 Comparative Efficacy and Safety of Subcutaneous Vedolizumab versus Other Targeted Inflammatory Bowel Disease Therapies in Patients With Moderate to Severe Ulcerative Colitis: A Network Meta-Analysis

S1149 Comparative Efficacy and Safety of Subcutaneous Vedolizumab versus Other Targeted Inflammatory Bowel Disease Therapies in Patients With Moderate to Severe Ulcerative Colitis: A Network Meta-Analysis

Clinical profile and short-term outcomes of acute severe ulcerative colitis in Vietnam: insights from a resource-limited setting.

Acute severe ulcerative colitis (ASUC) is a significant complication of ulcerative colitis, affecting roughly 25% of patients and increasing the risk of colectomy and hospital mortality. While intravenous steroids are a primary treatment, only 67% of patients respond, necessitating rescue therapy for non-responders. Data on ASUC in the Vietnamese population are scarce. This study aims to provide insights into the clinical characteristics and short-term outcomes of Vietnamese patients with ASUC. We conducted a prospective case series on ASUC patients admitted to the University Medical Center in Ho Chi Minh City from January 2021 to June 2023. Steroid response was assessed using the Travis Oxford criteria. We evaluated clinical features, in-hospital steroid response rates, endoscopic remission, and colectomy rates 12 months post-hospitalization. Seventeen patients with a median age of 42 years (70.6% male) were included. The median time from symptom onset to diagnosis was six weeks, and 47.1% had a history of ulcerative colitis. Median CRP value was 75.8 mg/L, and 76.5% had fecal calprotectin concentrations above 800 µg/g. All patients had a Mayo endoscopic subscore of ≥2, with 12.5% showing deep ulcers. Eleven patients (64.7%) responded to in-hospital steroid treatment, while 6 (35.3%) required rescue therapy with infliximab or tofacitinib. After one year, 10 of 11 (90.1%) achieved mucosal healing, and no patients underwent colectomy. Corticosteroids remain the cornerstone for initial ASUC therapy, though many patients do not respond. Anti-TNF agents and tofacitinib show potential benefits for those unresponsive to steroids. This study highlights the effectiveness of corticosteroids and biologics in managing ASUC in Vietnam.

S1427 A Single Center Experience of Upadacitinib Treatment for Acute Severe Ulcerative Colitis

S1427 A Single Center Experience of Upadacitinib Treatment for Acute Severe Ulcerative Colitis