Steroid-dependent Ulcerative Colitis Research Articles

P631 Effectiveness of Early Thiopurine Use in Korean Patients with Moderate-to-Severe Ulcerative Colitis: A Prospective Multicenter Cohort (MOSAIK) study

Abstract Background Thiopurines play an important role in the management of steroid-refractory steroid-dependent ulcerative colitis (UC). However, the effectiveness of the early use of thiopurines in UC remains controversial. Methods In this multicenter prospective cohort study, we divided patients with UC into those who underwent early (within 6 months of diagnosis) and late (6 months after diagnosis) thiopurine therapy to determine the effectiveness of early thiopurine treatment. The primary outcome was the cumulative rate of clinical relapse (Mayo score >2 points). Multivariate Cox proportional hazards regression was used to identify independent clinical factors associated with the outcomes. Results Overall, 333 patients with moderate-to-severe UC were included in the MOSAIK study. Of the 118 patients treated with thiopurines, 65 (55.1%) and 53 (44.9%) received thiopurine therapy within and after 6 months of diagnosis. The cumulative use rate of thiopurines was 38.96% at 3 years after diagnosis. The median initial dose of thiopurines was 0.7 mg/kg (0.3–2.0), and the median maintenance dose was 1.1 mg/kg (0.3–2.4). The cumulative rate of clinical relapse was not significantly different between patients who started thiopurine therapy within 6 months of diagnosis and those who started therapy 6 months after diagnosis during a 3–year period (p = 0.712). Multivariate analysis showed that the presence of extraintestinal manifestations (hazard ratio [HR]: 4.674, 95% CI: 1.210–18.061, p = 0.025) independently predicted an increased risk of clinical relapse. Conclusion Patients with UC who received early thiopurine therapy did not differ significantly in terms of clinical relapse compared with those who received late therapy.

Fatal pulmonary hemorrhage, pneumothorax and skin necrosis caused by IRIS to an Aspergillus flavus infection in a young patient with metamizole associated agranulocytosis

We report the case of a young female with steroid-dependent ulcerative colitis (UC) who developed a complex systemic infection with Aspergillus flavus. This occurred following a UC relapse while vacationing in the Middle East, leading to extended use of metamizole and subsequent agranulocytosis. On her return to Germany, she was hospitalized for neutropenic sepsis and later transferred to our hospital due to persistent cytopenia and suspected Hemophagocytic Lymphohistiocytosis (HLH). Despite initial stabilization with targeted treatment for pulmonary Aspergillus flavus infection, her condition rapidly deteriorated following the onset of an Immune Reconstitution Inflammatory Syndrome (IRIS), which manifested as skin necrosis and pneumothorax after the replenishment of neutrophil granulocytes. The patient eventually died from an unmanageable pulmonary hemorrhage. Microscopy of skin necroses showed a massive presence of Aspergillus flavus, but tissue culture remained negative, suggesting effective antifungal treatment yet delayed phagocytosis due to agranulocytosis. This case underscores the need to consider IRIS in immunosuppressed patients who worsen despite aggressive and appropriately targeted treatment, highlighting its potential beyond the commonly recognized context in HIV-positive patients.

Vedolizumab as Rescue Therapy in Carboplatin-Gemcitabine-Induced Triggered Acute Severe Ulcerative Colitis Flare-Up

Approximately 20% of patients with ulcerative colitis (UC) develop acute severe UC (ASUC), for which intravenous systemic steroid therapy and possibly infliximab-based rescue therapy are generally imposed. However, there are no significant guideline recommendations on ASUC regarding vedolizumab as an alternative in this setting. A case report was presented where a patient with steroid-dependent UC developed ASUC induced by second-line chemotherapy. Treatment with intravenous methylprednisolone was imposed, but there was no reduction in bowel movements in the days following admission. Rescue therapy with infliximab was contraindicated because of the oncologic history. Surgical consultation, contraindicated colectomy, and administration of vedolizumab 300 mg were initiated. After infusion with vedolizumab, there was a significant reduction in bowel movements starting the day after infusion until normalisation of bowel movements within three days and the concomitant normalisation of inflammatory indices. The patient is currently in clinical remission, on therapy with vedolizumab 108 mg subcutaneously every two weeks, and is in oncologic follow-up for pulmonary neoplasm. This case highlights the novel potential of vedolizumab as a possible rescue therapy in ASUC, especially in special populations, where it may offer a better safety profile. Although cyclosporine and infliximab still represent the mainstays of salvage therapy for steroid-refractory ASUC, new therapeutic agents may also be effective, such as vedolizumab, ustekinumab, and anti-Janus kinase agents.

P771 Biologics versus azathioprine in steroid-dependent ulcerative colitis: results from the A.U.R.O.R.A. database

Abstract Background The A.U.R.O.R.A. database is an Italian multicenter retrospective cohort of patients with ulcerative colitis (UC) treated with the first biological drugs (infliximab biosimilar- IFX-B, adalimumab-ADA, golimumab-GOL, vedolizumab-VDZ) approved in Italy after patent expire of IFX-originator. In a previous published study,1 we showed similar efficacy among all drugs according to the rigorous outcome of 1-year “continuous clinical remission” (CCR). In this study, we focused only on steroid-dependent UC, by comparing all drugs to each other and to patients treated with steroids followed by azatioprine (AZA) monotherapy. Methods All consecutive patients with steroid-dependent UC, treated with IFX-B, ADA, GOL or VDZ after their approval in 2014-2019, were followed-up for 1 year or until drug discontinuation for relapse or adverse events. All drugs were compared to each other and to steroid-dependent patients treated with steroids + AZA in 2006-2014. A propensity score analysis was performed to balance differences at baseline. The primary endpoint was the 1-year CCR, defined as steroid-free clinical remission with Mayo partial score ≤2 (with no bleeding), without any clinical relapse or treatment optimization after the first remission was achieved, and without drug withdrawal due to adverse events. Treatment optimization was defined as the addition of systemic/topical steroids, oral/topical mesalazine or any dose escalation of biologics Results 370 patients (IFX-B=62, ADA=68, GOL=56, VDZ=100, AZA 84) with steroid-dependent UC were included. No significant differences were found among each biological drug according to the 1-year CCR primary end-point (34%, 29%, 30%, 39%, respectively). In patients naive to immunesuppressors and biologics (n= 17, 25, 24 10, 79, respectively), AZA showed significantly higher rate of CCR (68%) than each biological drug (35%, 44%, 33%, 60%; p=0.000 for each comparison) or all biologics as a whole (41%; p=0.012). Adverse events occurred significantly less frequently with ADA (8%) than IFX (29%), GOL (20%) and AZA (26%) in the overall population, but were similar across all drugs in the naive population. Discontinuation for adverse events occurred more frequently (p<0.05) with both IFX-B (16%) and AZA (14%) than ADA (3%), GOL (4%), and VDZ (1%) in the overall population, but not in the naive population (18%, 15%, 4%, 4%, 0%, respectively). Conclusion In steroid-dependent UC, anti-TNF-alpha agents and VDZ were equally effective at 1 year according to the concept of CCR. AZA still appears an effective first-line strategy in the biological era. 1Cassinotti A. et al. Eur J Gastroenterol Hepatol. 2022;34:1238-46. Guided Poster Session

The Effects of Multi-Donor Fecal Microbiota Transplantation Capsules Combined with Thalidomide on Hormone-Dependent Ulcerative Colitis.

This study aimed to assess the effects of multi-donor fecal microbiota transplantation (FMT) capsules combined with thalidomide on hormone-dependent ulcerative colitis (UC). A total of 59 patients with steroid-dependent UC treated at the Gastroenterology Department of the First Affiliated Hospital of Xinxiang Medical University between January 2017 and January 2019 were enrolled in this study. Using a random number table, the patients were divided into two groups: a group treated with FMT capsules (the FMT group) and a group treated with FMT capsules and thalidomide (the FMT+S group). Multi-donor FMT capsules were prepared, and all subjects and stool donors followed the FMT pathway for FMT transplantation. Each patient's Mayo score, C-reactive protein (CRP) level, and level of fecal calprotectin before FMT treatment and at week 1 and week 13 after treatment were recorded. All patients were followed up for 15 weeks. A total of 56.7% of the patients (34/59) achieved a therapeutic response at the end of the research period. Compared with the FMT group, the FMT+S group had better clinical benefit (P < 0.05). In the comparison of efficacy at week 1 and week 13 after treatment, the Mayo scores, calprotectin levels, and CRP indexes in the FMT+S group were better than those in the FMT group (P < 0.05). There were no serious adverse events in the treatment process or during follow-up. A combination of FMT capsules and thalidomide provides a treatment choice for patients with hormone-dependent UC, and it can be used as an adjuvant therapy. However, large-scale, multi-center, and prospective trials are required to further verify the reliability of this treatment.

Optimal Placement of Colectomy in the Treatment of Ulcerative Colitis: a Markov Model Analysis

BackgroundTreatment for moderate-to-severe ulcerative colitis (UC) includes medical therapies such as immunosuppressive agents or surgical options such as colectomy. While prior studies have indicated a mortality benefit with elective surgery, the timing and effectiveness of colectomy in the UC treatment algorithm have not been assessed. We hypothesize that the ideal placement of colectomy occurs prior to the exhaustion of all medical therapies. MethodsWe designed a Markov model to assess the ideal position of colectomy. The base case was a 50-year-old male with steroid-dependent moderate-to-severe UC without prior treatment with immunomodulator or biologic therapies. We developed 4 separate algorithms incorporating elective colectomy: (1) prior to biologics, (2) after infliximab monotherapy failure, (3) after infliximab and azathioprine combination therapy failure, and (4) after medically refractory to all medical therapies including vedolizumab. Transition probabilities were obtained from published literature. First-order Monte Carlo simulations of 100 trials of 100,000 individuals were used to calculate quality-adjusted life-year (QALY) estimates. One-way sensitivity analyses were conducted for all variables. ResultsAlgorithm 3 (colectomy following combination therapy) was the preferred strategy with 1.864 QALYs (95% CI [1.863, 1.865]) over a 3-year period and the preferred strategy in the probabilistic sensitivity analysis 92.77% of the time. ConclusionsThis simulation suggests that early incorporation of colectomy for patients medically refractory to infliximab and azathioprine combination therapy may yield greater quality of life for patients with steroid-dependent UC. These findings suggest avenues for more patient-centered preference work and a combined medical-surgical approach to UC.

P066 Exploration of critical molecules for optimizing treatment by analyzing in flammatory cytokines in the intestinal mucosa of patients with Inflammatory Bowel Disease

Abstract Background Inflammatory cytokines initiate and sustain the perpetuation of processes leading to chronic inflammatory conditions such as inflammatory bowel diseases (IBD). Research into the cytokine biology of IBD has nurtured the dogmatic view that distinct immunotypes characterize different IBD subtypes. Recently, many biologics have emerged as the treatment options for IBD patients. Still, it is challenging to establish biomarkers for predicting their effectiveness because the cytokines that determine the IBD clinical phenotype vary in individual patients. Therefore, this study aims to explore critical molecules for optimizing treatment by analyzing inflammatory cytokines in the intestinal mucosa of IBD patients. Methods From September 2019, to February 2020, patients with ulcerative colitis (UC) and Crohn’s disease (CD) who underwent colonoscopy or flexible sigmoidoscopy, and the control group, patients who received colorectal polypectomy at our institution, were enrolled in the study. We took biopsies from inflamed ileal or colonic mucosa. We analyzed the gene expression of various inflammatory cytokines by real-time PCR using RT2 Profiler PCR Array (96-Well Format) Human Inflammatory Cytokines &amp; Receptors (QIAGEN). Cytokines not included in this array were subjected to real-time PCR separately. Based on these data, we investigated the relationship between mucosal cytokines and clinical characteristics. Results The total number of patients was 23 (control 5, UC 12, CD 6) cases, the median age was 51 years (18–78), genders were fifteen males and eight females. Disease phenotype was divided into extensive colitis/ left-sided colitis/proctitis (10/1/1) in UC patients, and A1/A2/A3 (2/3/1), L1/L3 (2/4), B1/B1+p/B2/B3 (3/1/1/1) in CD patients. Seven patients were steroid-dependent, and six patients were refractory to the anti-TNFα agent. The higher gene expressions of CCR2/CXCL1/CXCL3/CXCL13, IL-8, IL-33, and SPP1 in inflamed mucosa of UC compared to those of CD (p&amp;lt;0.05). The positive correlation between Mayo score and IL-1R1 expression in intestinal mucosa was observed (r=0.68, p=0.028). The expression of IL-1β, IL-6, IL-8, and oncostatin M (OSM) was higher in steroid-dependent UC patients, and the primary non-responders to anti-TNFα therapies had higher expressions of IL-7 in colonic mucosa than the secondary non-responders in UC. Conclusion Our results suggest that UC exhibits different cytokine patterns in the intestinal mucosa from CD as reported previously. Exploration of cytokine expressions in the intestinal mucosa may lead to predicting refractory IBD. The identification of molecules that can predict therapeutic effectiveness helps to optimize IBD treatment in the future.

P588 Steroid sparing effect of adalimumab in cortisone–depended ulcerative colitis patients

Abstract Background Corticosteroids are indicated for induction of remission in moderate to severe ulcerative colitis (UC) patients. However, due to their adverse effects associated with long-term use, steroids are not indicated as a maintenance therapy. The aim of this study was to assess the steroid sparing effect of adalimumab (ADA) in steroid-dependent UC patients. Methods This is a prospective study carried out at a tertiary hospital center in Albania from 2016–2020, including consecutive moderate-to-severe UC patients. All patients received biologic therapy with subcutaneous ADA 160/80mg at weeks 0/2 followed by 40mg every 2 weeks. We evaluated the steroid-sparing effect of ADA measuring the number of steroid–free patients and the average steroid dose at baseline before initiating biologic treatment and at week 8, 24, 52, 104, 156. Clinical remission was defined as total Mayo score ≤ 2 points. Results We enrolled 26 UC patients, mean age 47.3 ± 16.1 (24–85) years, 55.6% were females. The average disease duration before starting ADA was 7.3 ± 7.0 years (range 1–33); 44.4% had pancolitis and 55.6% left side colitis. 8(29.6%) patients were on combination therapy with azathioprine. 17/26 (65.4%) patients were taking prednisone at the time of the first ADA injection with an average dose of 17.7mg. The number of steroid-free patients at week 8, 24, 52, 104 and 156 was 12/26 (46.2%), 16/26 (61.5%), 15/21 (71.4%), 11/14 (78.6%), 8/9 (88.9%) respectively. At the end of the follow-up (week 156), the proportion of steroid free patient was significantly higher than at baseline [88.9% (8/9) vs 34.6% (7/26), p=0.005]. The reduction of the average dose of prednisone (8.8 mg, 4 mg, 6.8mg, 3.8mg and 3,8mg at week 8, 24, 52, 104 and 156 respectively), was also statistically significant (p&amp;lt;0.01). Clinical remission rates were 7.7% (2/26) at week 8, 47.6% (10/21) at week 52, 42.9% (6/14) at week 104 and 44.4 % (4/9) at week 156. Conclusion In our cohort, ADA administration to moderate–to severe UC significantly reduced the steroid dose and the proportion of patients taking cortisone during 3 years follow-up.

Cytapheresis re-induces high-rate steroid-free remission in patients with steroid-dependent and steroid-refractory ulcerative colitis.

BACKGROUNDIt is a crucial issue for patients with refractory ulcerative colitis (UC), including steroid-dependent and steroid-refractory patients, to achieve and maintain steroid-free remission. However, clinical studies focused on the achievement of steroid-free remission in refractory UC patients are insufficient. Cytapheresis (CAP) is a non-pharmacological extracorporeal therapy that is effective for active UC with fewer adverse effects. This study comprised UC patients treated with CAP and suggested the efficacy of CAP for refractory UC patients.AIMTo clarify the efficacy of CAP in achieving steroid-free remission in refractory UC patients.METHODSWe retrospectively reviewed the collected data from 55 patients with refractory UC treated with CAP. We analyzed the following points: (1) Efficacy of the first course of CAP; (2) Efficacy of the second, third, and fourth courses of CAP in patients who experienced relapses during the observation period; (3) Efficacy of CAP in colonic mucosa; and (4) Long-term efficacy of CAP. Clinical efficacy was evaluated using Lichtiger’s clinical activity index or Sutherland index (disease activity index). Mucosal healing was evaluated using Mayo endoscopic subscore. The primary and secondary endpoints were the rate of achievement of steroid-free remission and the rate of sustained steroid-free remission, respectively. Statistical analysis was performed using the paired t-test and chi-squared test.RESULTSThe rates of clinical remission, steroid-free remission, and poor effectiveness after CAP were 69.1%, 45.5%, and 30.9%, respectively. There were no significant differences in rate of steroid-free remission between patients with steroid-dependent and steroid-refractory UC. The mean disease activity index and Lichtiger’s clinical activity index scores were significantly decreased after CAP (P < 0.0001). The rates of steroid-free remission after the second, third, and fourth courses of CAP in patients who achieved steroid-free remission after the first course of CAP were 83.3%, 83.3%, and 60%, respectively. Mucosal healing was observed in all patients who achieved steroid-free remission after the first course of CAP. The rates of sustained steroid-free remission were 68.0%, 60.0%, and 56.0% at 12, 24, and 36 mo after the CAP. Nine patients (36%) had maintained steroid-free remission throughout the observation period.CONCLUSIONOur results suggest that CAP effectively induces and maintains steroid-free remission in refractory UC and re-induces steroid-free remission in patients achieving steroid-free remission after the first course of CAP.

Gastroenterologists' preference and risk perception on the use of immunomodulators and biological therapies in elderly patients with ulcerative colitis: an international survey.

Comorbidities, polypharmacy, malignancies, and infections complicate management of elderly patients with inflammatory bowel diseases (IBD). This study assessed gastroenterologists' preference in the prescription of medications or surgery to elderly patients with IBD, and the factors associated with their choices. An international case-based survey was conducted that presented three cases of steroid-dependent ulcerative colitis assessing young-age versus elderly-age patients, with and without comorbidity. Physician characteristics and practice demographics were collected. Factors associated with selection of different choices of therapy were determined by logistic regression analysis. A total of 424 respondents from 41 countries were included. Vedolizumab (53.2%) and thiopurines (19.4%) were the top treatment preferences for moderate-to-severe ulcerative colitis (P < 0.0001). Comorbidity and older age were independently associated with more frequent use of vedolizumab (P < 0.0001), and less frequent use of immunomodulators and anti-tumour necrosis factor (TNF; P < 0.0001). Comorbidity was the only independent predictor for selecting colectomy (P < 0.0001). A history of lymphoma (94%) and opportunistic infection (78.3%) were the most frequent conditions precluding the use of thiopurine and anti-TNF in elderly patients with IBD. Only 6.1% of respondents considered patient age a limit for vedolizumab, while 37.9% considered age as a limiting factor in prescribing thiopurines (P < 0.001). Geographical heterogeneity was identified with significantly more physicians from Oceania and North America favouring the use of vedolizumab. Vedolizumab was the preferred first-line agent in the treatment of elderly patients with IBD with steroid-dependent moderate-to-severe ulcerative colitis. Older age and presence of comorbidity influenced the selection of medication. Comorbidity was the main predictor of colectomy. Geographical heterogeneity in prescribing habits may relate to medication reimbursement in individual countries.

Chinese herbal medicine combination therapy for patients with steroid-dependent ulcerative colitis: Study protocol for a systematic review and meta-analysis.

Background:Ulcerative colitis (UC) is a chronic non-specific intestinal inflammatory disease characterized by continuous and diffuse inflammatory response of colonic mucosa. Steroid-dependent UC is an important type of UC. Chinese herbal medicine is widely used in treating steroid-dependent UC in China. However, there is no systematic review and meta-analysis to collate and evaluate the evidence of these studies. The purpose of this research is to provide evidence of the efficacy and safety of Chinese herbal medicine in treating steroid-dependent UC.Methods and analysis:Six databases, including 3 English databases and 3 Chinese databases will be searched. In addition, other grey literatures and ongoing studies will also be searched. Two researchers will independently select eligible studies by reading titles, abstracts and full texts according to the inclusion and exclusion criteria. Risk of bias assessment will be conducted by 2 independent reviewers using Cochrane risk-of-bias tool. The outcomes include steroid-free remission rate, Total clinical effective rate, Incidence of adverse events, Disease activity index (modified Mayo score), Results of enteroscopy (Baron score) and mucosa (geboes index score). Heterogeneity between studies will be assessed by Cochrane X2 and I2 tests. We will conduct subgroup analysis and meta-regression to explore the source of heterogeneity. We will also evaluate the stability of the results through sensitivity analysis and publication bias through funnel plot and Egger test.Results:The results will be published in peer-reviewed journals.Conclusion:Our meta-analysis and systematic evaluation results will confirm whether Chinese herbal medicine is effective in the treatment of steroid-dependent UC. It will provide more ideas for future research.OSF registration number:DOI: 10.17605/OSF.IO/YP79Z

Vedolizumab in patients with inflammatory bowel diseases of in real clinical practice

96 patients with IBD (62 with CD and 34 with UC) were prescribed therapy with vedolizumab at a dose of 300 mg intravenously at 0, 2, and 6 weeks, and further maintenance therapy was continued every 8 weeks. Most patients had prolonged inflammation (27 (79.4%) with total UC, 35 patients with CD (56.5%) had ileocolitis), resistance to therapy, including biological drugs (19 (55.9%) in patients with UC and 49 (79.0%) in patients with CD). The effectiveness of therapy was evaluated after 3 months (based on clinical response and clinical remission), 6 and 12 months (endoscopic response and endoscopic remission were additionally evaluated). After 3 months, clinical remission was observed in 62.5% and 36.6%, respectively. After 6 months, these indicators were 66.7% and 61.0%, and after 12 months, 70.8% and 61.0%, respectively. After 6 months, endoscopic remission was observed in 50.0% of UC patients and 26.8% of CD patients. After 12 months, it reached 58.3% and 31.7%, respectively. The analysis showed greater efficacy in bio-naive patients with CD (steroid-free remission after 12 months 62.5%, endoscopic remission 37.5%), as well as patients with non-stricturizing non-penetrating CD (58%). In patients with UC, vedolizumab showed the same effectiveness both in bio-naive patients (70.0%) and as a second-line therapy (71.2%). It turned out to be more effective in patients with moderate UC (76.2%) and steroid-dependent UC (77.8%). Vedolizumab is effective in achieving clinical response and clinical remission, as well as endoscopic response and endoscopic remission in patients with UC and CD. Given the selective mechanism of action of the drug, it can be recommended as a first-line therapy.

Corrigendum: Addition of Granulocyte/Monocyte Apheresis to Oral Prednisone for Steroid-dependent Ulcerative Colitis: A Randomized Multicentre Clinical Trial.

Background and Aims Steroid-dependency occurs in up to 30% of patients with ulcerative colitis [UC]. In this setting, few drugs have demonstrated efficacy in inducing steroid-free remission. The aim of this study was to evaluate the efficacy and safety of adding granulocyte/monocyte apheresis [GMA] to oral prednisone in patients with steroid-dependent UC. Methods This was a randomized, multicentre, open trial comparing 7 weekly sessions of GMA plus oral prednisone [40 mg/day and tapering] with prednisone alone, in patients with active, steroid-dependent UC [Mayo score 4-10 and inability to withdraw corticosteroids in 3 months or relapse within the first 3 months after discontinuation]. Patients were stratified by concomitant use of thiopurines at inclusion. A 9-week tapering schedule of prednisone was pre-established in both study groups. The primary endpoint was steroid-free remission [defined as a total Mayo score ≤2, with no subscore >1] at Week 24, with no re-introduction of corticosteroids. Results In all 123 patients were included [63 GMA group, 62 prednisone alone]. In the intention-to-treat analysis, steroid-free remission at Week 24 was achieved in 13% (95% confidence interval [CI] 6-24) in the GMA group and 7% [95% CI 2-16] in the control group [p = 0.11]. In the GMA group, time to relapse was significantly longer (hazard ratio [HR] 1.7 [1.16-2.48], P = 0.005) and steroid-related adverse events were significantly lower [6% vs 20%, P < 0.05]. Conclusions In a randomized trial, the addition of 7 weekly sessions of GMA to a conventional course of oral prednisone did not increase the proportion of steroid-free remissions in patients with active steroid-dependent UC, though it delayed clinical relapse.

Multi-session fecal microbiota transplantation using colonoscopy has favorable outcomes for the treatment of steroid-dependent ulcerative colitis.

Multi-session fecal microbiota transplantation using colonoscopy has favorable outcomes for the treatment of steroid-dependent ulcerative colitis.

Efficacy of fecal microbiota therapy in steroid dependent ulcerative colitis: a real world intention-to-treat analysis.

Background/AimsFour high-quality randomized controlled trials have proven the efficacy of fecal microbiota transplantation (FMT) in active ulcerative colitis (UC). We assessed the efficacy of FMT in a real-world setting involving steroid-dependent patients with UC.MethodsThis was a single-center prospective analysis of data from steroid-dependent patients with UC treated with FMT from September 2015 to September 2017 at the Dayanand Medical College, a tertiary care center in India. Fecal samples from random unrelated donors were administered through colonoscopy at weeks 0, 2, 6, 10, 14, 18, and 22. The primary outcome was achievement of steroid-free clinical remission, and the secondary outcomes were clinical response and endoscopic remission at 24 weeks. Modified intention-to-treat analysis was performed, which included subjects who underwent at least 1 FMT.ResultsOf 345 patients with UC treated during the study period, 49 (14.2%) had steroid-dependent UC. Of these 49 patients, 41 underwent FMT: 33 completed 7 sessions over 22 weeks according to the protocol, and 8 discontinued treatment (non-response, 5; lost to follow-up, 2; and fear of adverse effects, 1). At week 24, steroid-free clinical remission was achieved in 19 out of 41 (46.3%) patients, whereas clinical response and endoscopic remission were achieved in 31 out of 41 (75.6%) and 26 out of 41 (63.4%) patients, respectively. All patients with clinical response were able to withdraw steroids. There were no serious adverse events necessitating discontinuation.ConclusionsA multisession FMT via the colonoscopic route is a promising therapeutic option for patients with steroid-dependent UC, as it can induce clinical remission and aid in steroid withdrawal.

Hepatic Adenomatosis Complicated by Comorbid Steroid Dependent Ulcerative Colitis

Hepatic Adenomatosis Complicated by Comorbid Steroid Dependent Ulcerative Colitis

Combination Antibiotics Improves Disease Activity and Alters Microbial Communities in Children With Ulcerative Colitis.

Combinations of antibiotics have shown promise in off-label treatment of Inflammatory Bowel Disease (IBD) flares in adult and pediatric patients1–6. In a small pediatric cohort of moderate-severe medically refractory Ulcerative Colitis (UC), half achieved remission with a regimen of 3–4 antibiotics6. The rationale is to decrease mucosal inflammation by altering intestinal microbiota, however, to date no study has documented these changes. We report our experience with combination oral antibiotics in symptomatic pediatric patients with steroid-dependent or -resistant UC, and demonstrate significant alterations in gut microbiota during and after antibiotic therapy with reductions in inflammatory markers.

The Continental Divide: Anti-TNF Use in Pediatric IBD Is Different in North America Compared to Other Parts of the World.

Background and Aims Use of anti-TNF therapies varies internationally. As an initiative of the international Pediatric IBD Network (PIBDNet), we compared global pediatric IBD anti-TNF practice patterns. Methods Physicians were surveyed about anti-TNF use in Crohn's disease (CD) and ulcerative colitis (UC). Chi-squared, independent samples Mann–Whitney U, or related samples Wilcoxon signed rank tests were used to compare groups. Results 344 physicians treating pediatric IBD responded from 43 countries (54% North America, 29% Europe, 6% Oceania, 6% Asia, 3% Africa, and 2% South America). Respondents treated a median 40 IBD patients. CD was more commonly treated with anti-TNF than UC (40% vs. 10%, p<0.001). North Americans more often used anti-TNF (median 50% vs. 30%, p<0.001) and before immunomodulator (80% vs. 35% CD, p<0.001; 76% vs. 43% steroid-dependent UC, p<0.001). Anti-TNF monotherapy was more common in North America. Anti-TNF in combination with methotrexate, instead of thiopurine, characterized North American practices. North Americans more often continued immunomodulator indefinitely and less often adhered to standard infliximab induction dosing. Access limitations were more common outside North America and Europe for both CD (67% vs. 31%, p<0.001) and UC (62% vs. 33%, p<0.001). Conclusions Anti-TNF use in North America varies significantly from elsewhere.

Granulocyte/monocyte adsorptive apheresis for the treatment of therapy-refractory chronic active ulcerative colitis

Objectives: Current options for patients with steroid-dependent, chronic-active ulcerative colitis (UC) with insufficient response/intolerance to immunosuppressants (ISs) and/or biologics are limited. The aim of this study was to assess the long-term outcome of granulocyte/monocyte adsorptive (GMA) apheresis (Adacolumn®) in this population.Materials and methods: Ninety five adults with steroid-dependent active UC and insufficient response/intolerance to IS and/or TNF inhibitors received 5–8 aphereses in a single induction series of ≤10 weeks. Endpoints included rates of remission (clinical activity index [CAI] ≤ 4) at weeks 24 and 48.Results: Of 94 patients (ITT population), remission and response rates were 34.0% and 44.7% at week 24, and 33.0% and 39.4% at week 48. Among 30 patients with prior failure of IS and biologics, 33.3% and 20.0% were in remission at weeks 24 and 48. At both weeks, 19.2% of patients achieved steroid-free remission. Sustained remission or response occurred in 27.7% of patients at 48 weeks. The cumulative colectomy rate at week 96 was 23.4%. Safety was consistent with previous findings.Conclusions: This study confirms findings of the 12-week interim analysis and demonstrates that GMA apheresis provides a safe and beneficial long-term outcome for patients with chronic active UC resistant/intolerant to IS and/or TNF inhibitors.

Addition of Granulocyte/Monocyte Apheresis to Oral Prednisone for Steroid-dependent Ulcerative Colitis: A Randomized Multicentre Clinical Trial.

Steroid-dependency occurs in up to 30% of patients with ulcerative colitis [UC]. In this setting, few drugs have demonstrated efficacy in inducing steroid-free remission. The aim of this study was to evaluate the efficacy and safety of adding granulocyte/monocyte apheresis [GMA] to oral prednisone in patients with steroid-dependent UC. This was a randomized, multicentre, open trial comparing 7 weekly sessions of GMA plus oral prednisone [40 mg/day and tapering] with prednisone alone, in patients with active, steroid-dependent UC [Mayo score 4-10 and inability to withdraw corticosteroids in 3 months or relapse within the first 3 months after discontinuation]. Patients were stratified by concomitant use of thiopurines at inclusion. A 9-week tapering schedule of prednisone was pre-established in both study groups. The primary endpoint was steroid-free remission [defined as a total Mayo score ≤2, with no subscore >1] at Week 24, with no re-introduction of corticosteroids. In all 123 patients were included [63 GMA group, 62 prednisone alone]. In the intention-to-treat analysis, steroid-free remission at Week 24 was achieved in 13% (95% confidence interval [CI] 6-24) in the GMA group and 7% [95% CI 2-16] in the control group [p = 0.11]. In the GMA group, time to relapse was significantly longer (hazard ratio [HR] 1.7 [1.16-2.48], P = 0.005) and steroid-related adverse events were significantly lower [6% vs 20%, P < 0.05]. In a randomized trial, the addition of 7 weekly sessions of GMA to a conventional course of oral prednisone did not increase the proportion of steroid-free remissions in patients with active steroid-dependent UC, though it delayed clinical relapse.