Mild-moderate Ulcerative Colitis Research Articles

P1133 Safety and effectiveness of indigo naturalis for induction of remission in children with mild to moderate ulcerative colitis: a prospective open-label trial

Abstract Background Indigo naturalis (QingDai, QD) is effective in inducing remission in adults with ulcerative colitis (UC). However, data in pediatrics is limited and potential pulmonary hypertension and hepatitis remain a concern. In this prospective open-label study, we aimed to evaluate the efficacy and safety of QD for pediatric UC. Methods Children aged 4-18 years with mild-moderate UC (Pediatric Ulcerative Colitis Activity Index [PUCAI] 10-60) on stable medication, and not receiving steroids or biologics, were treated with QD for 6 weeks. Initial doses were weight-based (500/750/1000 mg/day for 20-30/30-40/40+ kg, respectively) with possible dose escalation at week 3. Echocardiography was performed at baseline and week 6. The primary outcome was corticosteroid-free remission at week 6 defined as PUCAI<10 and a ≥10-point reduction in PUCAI. Results were analyzed using intention-to-treat. Results Twenty children were enrolled (age 13.6±2.4 years, disease duration 7 [3-12] months, 50% female); all were treated at baseline with oral 5-ASA regimens. Two discontinued QD early (UC exacerbation, poor compliance), 18 completed the study and 9 required dose escalation at week 3. Clinical remission was achieved in 13 patients (65%). Calprotectin levels <250mg/kg and <100mg/kg at week 6 were observed in 13 (65%) and 10 (50%), patients, respectively. Significant reduction compared to baseline were noted in both PUCAI (30 [15-40] vs. 5 [5-15], p<0.01) and calprotectin (588 [305-1,137] vs 97 [44-438], p=0.03). Adverse events included headache (4 patients), vomiting (1) and nausea (1) and did not lead to treatment discontinuation. Mild transient hepatitis was noted in a single patient at week 3, and another patient had minimal ALT elevation at week 6. There was no evidence of pulmonary hypertension at week 6. Conclusion QD is effective in inducing remission in biologic-naïve children with mild-moderate UC. Headache was the most common adverse event; pulmonary hypertension was not observed. Additional efficacy and safety studies are required to determine whether QD can be used for maintenance.

The efficacy of curcumin/Qing Dai combination in children with active ulcerative colitis: a multicenter retrospective cohort study.

Curcumin and Qing Dai (QD) are herbal extracts that recently showed efficacy in treating inflammatory bowel disease (IBD). Since 2016, a combination of curcumin with QD (CurQD) has been employed in our center for management of active ulcerative colitis (UC). We report the effectiveness and safety of CurQD therapy in children with mild-moderate UC or IBD-unclassified (IBD-U). A multicenter retrospective study. Children aged ≤OP18 years who were treated with CurQD during 2017-2021 were included. Disease activity measures were Pediatric UC Activity Index (PUCAI), and fecal calprotectin (FC). The primary outcome was a decrease in PUCAI by ≥10 points, FC normalization (≤100 µg/gr when baseline ≥300 µg/gr) or a ≥ 50% decrease in FC. Of 30 patients (60% males, mean age 14 ± 3.9 years), 15 (50%), 13 (43%), and 2 (7%) had pancolitis, left-sided colitis and proctitis, respectively. The daily medication dose was 0.5-3 gm QD with 1-4 gm curcumin. Concomitant treatment at induction was corticosteroids (19%), biologics (28%) and 5-aminosalicylic acid (40%). The mean duration of induction was 11.6 weeks [95% confidence interval (CI) 10.2-13.1, range 8-16]. PUCAI decreased from a mean of 31.3 (95% CI 26.6-36.0, range 5-60) to 10.9 (95% CI 7.6-14.4, range 5-35) (n = 26, p < 0.001). FC response and normalization occurred in 11/12 and 7/12 patients, respectively. The median decline in FC was from 749 µg/gm [interquartile range (IQR) 566-1000] to 39 µg/gm (IQR 12-132) (n = 15, p = 0.04). During follow-up (median 8 months, IQR 6-10), 10 patients (33%) flared; five of them regained remission or responded to a treatment change. Of 18 patients treated beyond induction, 12 (67%) achieved clinical response and 10 achieved clinical remission by the end of follow up. CurQD may be effective and safe as an add-on option to conventional management, for induction and maintenance in children with mild-moderate UC/IBD-U.

P1041 Coconut water modulates dietary potassium and gut microbiome to induce remission in ulcerative colitis: randomized controlled trial

Abstract Background High potassium intake is associated with decreased risk of inflammatory bowel disease(IBD), urinary potassium has been correlated with disease activity in ulcerative colitis(UC), and gut microbiome modulation improves outcomes in UC. We evaluated coconut water as potassium rich diet and gut microbiome modulator in patients with mild-moderate UC. Methods This single-center double-blind placebo-controlled trial randomized patients with mild-moderate (simple clinical colitis activity index-SCCAI:3–9) endoscopically active UC (ulcerative colitis endoscopic index of severity-UCEIS&amp;gt;1) in 1:1 ratio to coconut water + standard medical therapy-SMT(CW) vs placebo + SMT. 400ml of coconut water (200-250mg potassium/100ml) was administered for 8 weeks. Primary outcome measure was clinical remission (SCCAI ≤ 2) and secondary outcome measures were clinical response (SCCAI decline ≥ 3) and adverse events at 8 weeks. Microbiome was analyzed at baseline and 8 weeks. Results Of 121 patients screened, 95 were included for modified intention to treat analysis(49-CW, 46-placebo)[mean age-37.2 ± 11.2years; males-54.1%; disease duration-48 (IQR:24–90) months; pancolitis - 26.1%; SCCAI-5 (IQR:4 – 6); UCEIS-4 (IQR:3 – 5)]. There was significant increase in dietary potassium and decline in sodium/potassium ratio at 8 weeks in CW. Clinical response [57.1% vs 28.3%, p=0.01, OR-3.4 (95%CI:1.4 – 7.9)], remission [53.1% vs 28.3%, p=0.02, OR-2.9(95%CI:1.2 – 6.7)] and proportion of patients with fecal calprotectin (FCP)&amp;lt;150μg/g [53.6% vs 14.3%, p=0.01, OR-6.9(95%CI:1.6 – 28.9)] were significantly higher in CW. The relative abundance of bacterial taxa which had a significant or trend towards negative correlation with SCCAI, UCEIS, or FCP, increased at 8 weeks in CW. Adverse events were comparable and no patient developed hyperkalemia. Conclusion Coconut water increased dietary potassium, modulated the gut microbiome and was more effective than placebo for induction of remission in mild-moderate UC.

Coconut Water Induces Clinical Remission in Mild to Moderate Ulcerative Colitis: Double-blind Placebo-controlled Trial

Background and AimsCoconut water is anti-inflammatory, can manipulate the gut microbiome and is a rich source of potassium. Gut microbiome modulation improves outcomes in UC, and potassium possesses in vitro anti-inflammatory property. We evaluated the effect of coconut water as an adjunct therapy for patients with mild-moderate UC. MethodsThis single-center double-blind placebo-controlled trial randomized patients with mild-moderate(simple clinical colitis activity index-SCCAI:3–9) endoscopically active UC(ulcerative colitis endoscopic index of severity-UCEIS>1) in 1:1 ratio to coconut water + standard medical therapy-SMT(CW) vs placebo + SMT. 400ml of coconut water was administered for 8weeks. Primary outcome measure was clinical remission(SCCAI ≤2) and secondary outcome measures were clinical response(SCCAI decline ≥3) and adverse events at 8weeks. Microbiome was analyzed at baseline and 8weeks. ResultsOf 121 patients screened, 95 were included for modified intention to treat analysis(49-CW, 46-placebo)[mean age-37.2±11.2years; males-54.1%; disease duration-48(IQR:24–90)months; pancolitis-26.1%; SCCAI-5(IQR:4 – 6); UCEIS-4(IQR:3 – 5)]. Clinical response[57.1% vs 28.3%, p=0.01, OR-3.4(95%CI:1.4 – 7.9)], remission[53.1% vs 28.3%, p=0.02, OR-2.9(95%CI:1.2 – 6.7)] and proportion of patients with fecal calprotectin(FCP)<150μg/g[30.6% vs 6.5%, p=0.003, OR-6.3(95%CI:1.7 – 23.6)] were significantly higher in CW. The relative abundance of bacterial taxa which had a significant or trend towards negative correlation with SCCAI, UCEIS, or FCP, increased at 8weeks in CW, and this effect was independent of disease activity and dietary fiber. Adverse events were comparable and no patient developed hyperkalemia. ConclusionCoconut water was more effective than placebo for induction of clinical remission in patients with mild to moderate UC.The trial was prospectively registered on clinical trials registry India (No: CTRI/2019/03/01827)

DOP67 MB310: From Clinical FMT to a Phase 1 Study with a Defined, Orally Administered Live Bacterial Therapeutic for Mild Moderate Ulcerative Colitis

Abstract Background The composition of the gut microbiome is a key determinant in inflammatory bowel disease. Consequently, modifying the composition of the gut microbiota has the potential to transform the treatment of ulcerative colitis (UC). The clinical use of faecal microbiota transplantation (FMT) has become widespread, especially for the treatment of C. difficile associated diseases, as a method of changing the composition of the gut microbiome from a diseased to a healthy state. FMT is, by its nature, an undefined and variable therapy due to differences between donors. Microbiotica has taken a "patient-first" discovery approach to identify a defined consortium, which is being developed as a live bacterial therapeutic for treatment of mild-to-moderate UC patients in a Phase 1b clinical trial, the COMPOSER-1 study, in 2024. Methods A clinical trial in UC patients (Costello et al., 2019), in which patients were treated with FMT from healthy donors, showed a 32% clinical remission rate in the active treatment group, as compared to 9% in the placebo arm. Donor, pre-treatment recipient, and post-FMT recipient samples were analysed using shotgun metagenomic sequencing. All samples were analysed using Microbiotica’s precision microbiome analysis platform to identify bacteria associated with patient response. These bacteria were assessed in cellular assays using relevant human cell/cell lines including: Caco2, dendritic cells, M1 macrophages, and CD4+ T-cells. Results We defined a signature of therapeutic response based on bacteria that engrafted from the donor into UC patients and were associated with clinical benefit. A sub-species level analysis identified 8 bacteria, which have been developed into a defined live bacterial therapeutic, MB310. The consortium bacteria enhanced the barrier integrity of an epithelial cell monolayer, and protected the barrier from inflammatory challenge by LPS. In vitro, the bacteria also have an anti-inflammatory effect when incubated with different primary innate immune cells, dendritic cells and M1 macrophages. Specific MB310 bacteria, either directly or via metabolites, are able to regulate T-cell responses. Conclusion In summary, we have identified a consortium of bacteria using patient-first discovery in a successful FMT study that is being developed as a treatment for UC. The consortium of 8 bacteria is able to impact multiple disease-relevant mechanisms including epithelial barrier integrity and immunomodulation. MB310 is being advanced to a first-in-human study in 2024 to explore safety and initial signs of efficacy. Costello, et al. (2019) Jama 321.2: 156-164.

Gut microbiota-derived 12-ketolithocholic acid suppresses the IL-17A secretion from colonic group 3 innate lymphoid cells to prevent the acute exacerbation of ulcerative colitis

ABSTRACT Intestinal microbiota dysbiosis and metabolic disruption are well-known as the primary triggers of ulcerative colitis (UC). However, their role in regulating the group 3 innate lymphoid cells (ILC3s), which are essential for intestinal health, remains unexplored during the development of disease severity. Here, our results showed that the microbiota structure of patients with severe UC (SUCs) differed from those with mild UC (MiUCs), moderate UC (MoUCs), and healthy controls (HCs). Microbes producing secondary bile acids (SBAs) and SBAs decreased with the aggravation of UC, and a strong positive correlation existed between them. Next, fecal microbiota transfer was used to reproduce the human-derived microbiota in mice and decipher the microbiota-mediated inflammatory modulation during an increase in disease severity. Mice receiving SUC-derived microbiota exhibited enhancive inflammation, a lowered percentage of ILC3s, and the down-regulated expressions of bile acid receptors, including vitamin D receptor (VDR) and pregnane X receptor (PXR), in the colon. Similar to clinical results, SBA-producing microbes, deoxycholic acids (DCA), and 12-ketolithocholic acids (12-KLCA) were diminished in the intestine of these recipients. Finally, we compared the therapeutic potential of DCA and 12-KLCA in preventing colitis and the regulatory mechanisms mediated by ILC3s. 12-KLCA but not DCA represented a strong anti-inflammatory effect associated with the higher expression of VDR and the lower secretion of IL-17A from colonic ILC3s. Collectively, these findings provide new signatures for monitoring the acute deterioration of UC by targeting gut microbiota and bile acid metabolism and demonstrate the therapeutic and preventive potential of a novel microbiota-derived metabolite, 12-KLCA.

Comparative efficacy and tolerability of probiotic, prebiotic, and synbiotic formulations for adult patients with mild-moderate ulcerative colitis in an adjunctive therapy: A network meta-analysis

Background & aimsProbiotics, prebiotics, and synbiotics (PPS) have been widely used as adjuvant treatments in patients with ulcerative colitis (UC) in recent years. However, the most effective formulations of PPS have yet to be identified. We thus aimed to compare the efficacy and tolerability of different PPS formulations for mild-moderate UC. MethodsWe searched PubMed, Embase, Web of Science, and Cochrane CENTRAL from inception to June 24, 2023 for double-blind randomized controlled trials. We used a frequentist approach in random-effects models for network meta-analysis and the Grading of Recommendations Assessment, Development, and Evaluation approach to evaluate the certainty of evidence. ResultsWe analysed data from 20 trials involving 1153 patients. The combinations of specific strains of Lactobacillus and Bifidobacterium (CLB) (odds ratio (OR), 3.85; 95% confidence interval (CI), 1.40-10.60; low certainty) and combinations of specific strains of Lactobacillus, Bifidobacterium, and Streptococcus (CLBS) (OR, 2.20; 95% CI, 1.47-3.28; low certainty) significantly increased the clinical remission rate in intention-to-treat analysis (ITT) when compared to placebo. Similarly, compared with placebo, the two combinations significantly reduced clinical activity scores (standardized mean difference (SMD), -1.17 (95% CI, -1.68 to -0.65), low certainty; and SMD, -1.33 (95% CI, -1.81 to -0.86), low certainty, respectively). Hierarchical cluster analyses showed the two combinations formed clusters with high efficacy (clinical remission in ITT and clinical activity score) and tolerability (withdrawal due to worsening symptoms) within 12 weeks. ConclusionIn this systematic review, we found CLB and CLBS demonstrated a clinical benefit in adjuvant treatments, with a comparable tolerability and safety profile to placebo. Further trials are needed.Trial registration number: CRD42022344905

P908 Faecal Microbiota Transplantation refurbishes the crypt-associated microbiota in Ulcerative colitis

Abstract Background Intestinal crypts form a pristine gut biogeographical niche, homing the intestinal stem cells and being the closest neighbors to underlying lamina propria. Initially believed to be sterile, the crypt lumen was recently shown to inhabit a conserved microbial population. However, the identity of the crypt-associated microbiota (CAM) remains elusive. The present study is among the first to illustrate the CAM composition in health and its deviation during ulcerative colitis (UC), and the effect of faecal microbiota transplantation along with an anti-inflammatory diet (FMT-AID) on the structure of this community. Methods Recto-sigmoidal biopsies from controls, and from patients with mild-moderate UC before and after FMT-AID (n=26), were subjected to methacarn-fixation, followed by paraffin-embedding, sectioning and laser-capture microdissection-assisted crypt isolation. DNA isolated from micro-dissected samples was subjected to 16S rRNA gene sequencing. The bacterial presence in colonic crypts was confirmed using fluorescence in-situ hybridization(FISH). Microbiome data analysis was carried out by using QIIME2 and R packages. Results FISH performed using pan-bacterial probes revealed the presence of sparse microbial clusters in colonic crypts, distinct from the overlying layer of Mucosa-associated microbiota (MAM), in both controls as well as in UC(Fig.1a and 1b). While MAM is dominated by members of phyla Firmicutes (45%) and Bacteroidetes (26%),CAM is comprised predominantly of aerobic members of Actinobacteria(54%) and Proteobacteria(38%), followed by minor proportions of Firmicutes(4%), Acidobacteria and Cyanobacteria (2% each). The significant members of CAM included aerobic genera -Cutibacterium(35%),Sphingobium(13%), Paracoccus(11%), Micrococcus(3%), Lawsonella(3%), Rothia(2%), Prauserella(2%), Kocuria, Corynebacterium, Acinetobacter and Brevundimonas (1% each)(Fig.1c and 1d). Analysis of CAM diversity in controls, and in patients with UC before and after FMT-AID, showed no significant alterations in the α- and β diversity matrices(Fig.1e and 1f).CAM demonstrated UC-associated dysbiosis of specific taxa which was restored after FMT-AID(Fig.2a and 2b). These FMT-restored CAM taxa correlated negatively with disease-associated parameters - Fecal calprotectin (FCP), Simple Clinical Colitis Activity Index (SCCAI) and Ulcerative Colitis Endoscopic Index of Severity (UCEIS)(Fig.2c and 2d). The positive effects of FMT-AID further refurbished the CAM-MAM interaction networks, which were obliterated in UC.(Fig.2e) Conclusion A gut bacterial community, enriched in aerobic bacteria, resides in the colonic crypts, and undergoes taxa-level alterations during UC and in response to FMT.

Micronutrient deficiency among patients with ulcerative colitis

Background and aimMalnutrition is a common problem among patients with inflammatory bowel disease and up to 18–62% of ulcerative colitis (UC) patients were reported to be malnourished. This study aimed to assess micronutrient status among naïve UC patients and its correlation with disease severity.MethodsA prospective case-control study carried out on 46 patients who visited our endoscopy unit between April 2019 and April 2021. The patients were classified into 3 groups of mild, moderate, and severe UC based on colonoscopy findings, and histopathological examination. Serum was collected and assayed for levels of iron, magnesium, zinc, selenium, and copper.ResultsForty-six (17 male, 29 female) patients divided into 2 groups (23 naïve UC patients and 23 healthy individuals) with the mean age of 32 years were included in the study. The serum levels of magnesium, zinc, and selenium were significantly lower in the UC group (p < 0.001, 0.018 and < 0.001, respectively). However, iron and copper levels were not significantly different between the 2 groups. In discriminating severe from mild-moderate UC cases, there was a statistically significant result of magnesium at cutoff 1.8 or less in discriminating severe from mild to moderate UC cases with an AUC of 0.950 and p value of < 0.001.ConclusionMicronutrients should be assessed in patients in UC patients to alert to the fact that correction of these deficiencies could facilitate achievement of remission. Further research is needed to confirm if magnesium levels could serve as a predictor of the disease severity.

Non-invasive monitoring and treat-to-target approach are cost-effective in patients with mild-moderate ulcerative colitis.

There are no data to assess the value associated with a treat-to-target (T2T) strategy based on tight control of mild-moderate ulcerative colitis (UC). To assess the cost-effectiveness of a T2T approach based on the normalisation of clinical signs and faecal calprotectin (FC) METHODS: A decision analytical Markov model was developed to compare T2T algorithm combining clinical symptoms and FC levels to define treatment response and the possible switch to the next treatment line (T2T-FC), and the reference strategy based only on symptoms. The model included five treatment lines and was conducted from the Italian national health service (NHS) perspective using a 3-year time horizon. The model calculated the incremental cost-effectiveness ratio as € per relapse avoided. Deterministic and probabilistic sensitivity analyses were conducted. The cost-effectiveness analysis produced an increased time spent by a patient in clinical remission and FC ≤ 100 level (+0.177 years; about 2months) and a decreasing number of relapses (-0.1937; -20.9%) per patient using a T2T-FC approach compared to only symptoms. Furthermore, the T2T-FC was associated with higher cost (+€1795). The ICER estimated was €9263 per relapse avoided. These results were confirmed by sensitivity analyses. T2T-FC approach resulted in a higher benefit for mild-moderate UC patients in terms of time in remission and incidence of relapse but was associated with higher costs. Clinical trials and real-world clinical studies are needed to provide additional data on the cost-benefit of this approach.

Faecal microbiota transplantation with anti-inflammatory diet (FMT-AID) followed by anti-inflammatory diet alone is effective in inducing and maintaining remission over 1 year in mild to moderate ulcerative colitis: a randomised controlled trial

ObjectiveMicrobiome and dietary manipulation therapies are being explored for treating ulcerative colitis (UC). We aimed to examine the efficacy of multidonor faecal microbiota transplantation (FMT) and anti-inflammatory diet in inducing...

Drug therapy and monitoring for inflammatory bowel disease: a multinational questionnaire investigation in Asia.

Background/Aims The incidence and prevalence of inflammatory bowel disease (IBD) is rising in Asia recently. The study aimed to obtain a comprehensive understanding of the current status of drug therapy and monitoring for IBD in Asia.Methods A questionnaire investigation on drug therapy and monitoring for IBD was conducted right before the 6th Annual Meeting of Asian Organization for Crohn’s & Colitis. Questionnaires were provided to Asian physicians to fill out via emails between March and May 2018.Results In total, responses of 166 physicians from 129 medical centers were included for analysis. Among the surveyed regions, the most average number of IBD specialist gastroenterologists and nurses was 4.8 per center in Taiwan and 2.5 per center in Mainland China, respectively. 5-Aminosalicylic acid/sulfasalazine (99.4%) was the most preferred first-line choice for mild-moderate ulcerative colitis (UC), meanwhile corticosteroid (83.7%) was widely applied for severe UC. The first-line medication for Crohn’s disease (CD) markedly varied as corticosteroid (68.1%) was the most favored in Mainland China, Japan, and South Korea, followed by infliximab (52.4%) and azathioprine (47.0%). Step-up strategy was preferred in mild-moderate UC (96.4%), while 51.8% of the physicians selected top-down treatment for CD. Only 25.9% and 17.5% of the physicians could test blood concentration of infliximab and antibody to infliximab in their hospitals, respectively.Conclusions The current status of drug therapy and monitoring for IBD in Asia possesses commonalities as well as differences. Asian recommendations, IBD specialist teams and practice of therapeutic drug monitoring are required to improve IBD management in Asia.

Specific alterations in mucosa-associated bacterial composition in ulcerative colitis (UC) patients with different degrees of inflammation

The aim of this study is to evaluate the specific bacterial communities and alterations and to explore the method predicting the microbiological evolution tendency of ulcerative colitis (UC) patients. A total of 29 UC patients and 18 healthy subjects (HS) were enrolled. UC patients were grouped into mild, moderate and severe UC based on the Mayo Score. The bacterial types of the groups were distinctly different with each other on different classification levels. Interestingly, the bacterial composition of severe UC was distinctly different from others. The Chao and Ace indices of bacterial microbiota were significantly higher in the severe UC group. The main phyla in UC and HS were Firmicutes, Bacteroidetes and Proteobacteria. The percentage of the 3 main phyla in severe UC was lower than that in non-severe UC. Similar to the other groups, the main genera in severe UC were Bacteroides and Escherichia-Shigella. However, Parabacteroides and a type of Prevotella disappeared in the severe UC group. Some types, such as Faecalibacterium and Fusobacterium, decreased. On the contrary, the other types increased. The abundance of the putative pathogenic bacteria in mild UC, moderate UC and severe UC showed an increasing trend (9:11:115). Moreover, Bacillus, Lactococcus and Alloprevotella disappeared in UC. Parabacteroides and a type of Prevotella disappeared in severe UC. Serious dysbacteriosis and abundant putative pathogenic bacteriа are the two important features of severe UC. The percentage phyla and the abundance of putative pathogenic bacteria could be used to predict the evolution tendency.

An update on fecal microbiota transplantation for the treatment of gastrointestinal diseases.

Our understanding of the microbiome and its implications for human health and disease continues to develop. Fecal microbiota transplantation (FMT) is now an established treatment for recurrent Clostridioides difficile infection. There is also increasing evidence for the efficacy of FMT in inducing remission for mild-moderate ulcerative colitis. However, for other indications, data for FMT are limited, with randomized controlled trials rare, typically small and often conflicting. Studies are continuing to explore the role of FMT for many other conditions, including Crohn's disease, functional gut disorders, metabolic syndrome, modulating responses to chemotherapy, eradication of multidrug resistant organisms, and the gut-brain axis. In light of safety, logistical, and regulatory challenges, there is a move to standardized products including narrow spectrum consortia. However, the mechanisms underpinning FMT remain incompletely understood, including the role of non-bacterial components, which may limit success of novel microbial approaches.

P602 Vedolizumab subcutaneous influencing disease course in Constant-care app solution

Abstract Background The Constant-care app solution (CC) has been shown to empower patients with mild-moderate Ulcerative Colitis (UC) in 5-ASA treatment and improve disease specific quality of life (1). Here we present preliminary data on our study to investigate the effects of CC on quality of life in patients with moderate-severe UC or Crohns Disease (CD) treated with s.c.vedolizumab, launched in June 2020 in Denmark. Methods The study is an ongoing non-interventional, observational study. Patients are homemonitored via CC for 24 months. CC shows data on patient’s disease status, grouping them into three: green (remission), yellow (worsening), red (severe disease). Patients were recruited from the outpatient clinic at the Department of Gastroenterology, North Zealand University Hospital, Greater Copenhagen. Simple Clinical Colitis Index (SCCAI), Harvey-Bradshaw Index (HB-I), Fecal calprotectin (FC) and short QoL (0–70) are measured every two months or during a flare up between fixed screenings. Serious adverse events (SAE) and adverse events (AE) are monitored. Results 19 patients out of 40 have been included, 8 with CD and 11 with UC. None experienced SAEs. Five experienced AEs, of which four discontinued treatment. One patient experienced treatment failure during this study. Of the 15 patients, two are in complete remission, (Q2 respectively Q3). Five of the remaining patients have not entered more than two data entries in CC (data not shown).All patients sustained remission based on FC, except for two data points for two individual patients. Good QoL ≥ 50 was almost unchanged for 6 patients. Conclusion IBD CC has proven a usefull tool for surveillance and maintenance of remission in IBD patients treated with s.c. vedolizumab. S.c. vedolizumab has in this patientgroup, shown to provide sustainable QoL, sustained remission, and to have few AEs. 1) Elkjaer M, Shuhaibar M, Burisch J, Bailey Y, Scherfig H, Laugesen B, et al. E-health empowers patients with ulcerative colitis: a randomised controlled trial of the web-guided ‘Constant-care’ approach. Gut. 2010;59(12):1652–61.

Risk factors and management strategies associated with non-response to aminosalicylates as a maintenance treatment in ulcerative colitis.

Aminosalicylates (5-ASA) are used as the first-line maintenance treatment in patients with mild-moderate ulcerative colitis (UC). Early identification of patients at high risk for 5-ASA non-response and appropriate therapeutic escalation are essential to avoid disease progression. However, the absence of a standardized definition for treatment success makes this a challenging task. The focus of the current review was to describe the risk factors and management strategies associated with 5-ASA non-response. Rates of 5-ASA failure can vary from 17 % to 75 % according to different success definitions, of which clinical relapse is the most prevalent and studied condition. Younger age and endoscopic activity at diagnosis, extensive colitis, early need for corticosteroids, elevated inflammatory markers and non-adherence are consistent risk factors of 5-ASA failure. Given the effectiveness, safety profile and tolerability of this medication, therapy optimization is critical before treatment escalation. Combined use of systemic and topical therapy at an appropriate dose in a once-daily administration and control of adherence could improve success rates.

Outcomes of a drug shortage requiring switching in patients with ulcerative colitis.

BACKGROUNDDrug shortages are common yet their impact on patient care and their commercial ramifications has not been adequately researched. In Australia a shortage of balsalazide (2012-2013) necessitated substitution with alternative 5-aminosalicylate (5-ASA) formulations for ulcerative colitis (UC).AIMTo assess and compare the clinical and commercial sequelae of non-medical switching from balsalazide to another 5-ASA and/or return to balsalazide once supply resumed.METHODSA prospective cohort study of patients on balsalazide for mild-moderate UC was conducted where, strictly due to the national shortage (November 2012- January 2013), were switched to alternative 5-ASA and/or then returned to balsalazide once supply resumed. Clinical (Partial Mayo), endoscopic (Mayo score) activity, adverse effects (to alternative 5-ASA) and percentage market share (of continuous 5-ASA users) from baseline (i.e., time of switching due to shortage) through to five years were assessed.RESULTSOf 31 patients switched due to the shortage, 12 (38.7%) resumed balsalazide immediately once supply resumed, 8 (25.8%) prompted by adverse effects to the alternative 5-ASA used. Three patients (9.7%) had documented symptomatic improvement, 15 (48.4%) were unchanged and 13 (41.9%) had symptomatic worsening vs baseline (P < 0.01), after switching to an alternative 5-ASA. At 3 and 5y post switch, overall 26/31 (83.9%) and 23/31 (74.2%) had remained continuously on any 5-ASA therapy respectively. Twelve (38.7%) and 11 (35.5%) patients remained on balsalazide continuously at three and five years respectively after drug supply returned, equating to a loss of market share (within 5-ASA class) of 45.2% and 38.7% respectively.CONCLUSIONThis study of a balsalazide shortage in UC patients exemplifies the detrimental impact of a drug shortage on long term patient, disease and commercial outcomes.

829 Appropriateness of Treatment Options in Mild to Moderate Ulcerative Colitis: A RAND Appropriateness Panel

INTRODUCTION: Treatment options for patients with moderate-severe ulcerative colitis (UC) are increasing. The appropriateness of their use in mild-moderate UC is less clear, as is the role of surgical intervention. Our aim was to define the appropriateness of therapeutic options in a range of clinical scenarios in mild-moderate UC METHODS: We applied the RAND/UCLA Appropriateness Method to rate appropriateness of treatment choices in patients with mild-moderate UC; severe disease (likely to need hospitalization or surgery within 2 weeks) was excluded. A literature review was presented to the BRIDGe group, a panel of 13 IBD specialists, as well as 1 external IBD expert and 2 IBD surgical experts. 12 chapters were constructed including failed 5-ASA, steroid or thiopurine therapy, and primary/secondary non-response to biologics or tofacitinib. Scenarios were also divided by disease extent (proctitis vs more extensive) and activity (mild vs moderate) creating 260 scenarios in all. Panellists used a modified Delphi method to anonymously rate the appropriateness of a therapy on a 1-9 scale (1-3 not appropriate, 4-6 uncertain, 7-9 appropriate). Disagreement was assessed using a validated index (DI) and was defined as a DI &gt; 1. The panellists then convened in person to discuss areas of disagreement, followed by a second round of rating. Scenarios rated a median of 7 or higher were deemed appropriate and those rated 3 or lower were deemed inappropriate. Scenarios rated 4-6 were considered uncertain, as were any with a DI &gt; 1 RESULTS: Appropriateness was agreed in 131 and inappropriateness in 47 scenarios. Greatest disagreement was around the use of thiopurines, but no scenario had a DI &gt; 1. There were 82 scenarios were rated uncertain. Biologics and tofacitinib were more likely to be rated appropriate for treatment resistance and greater disease activity; disease extent less likely to influence decision making. Surgery was felt to be appropriate in 8 scenarios, generally in more extensive and active disease that had failed to respond to medical therapy. Surgery was felt to be inappropriate in 16 scenarios and was uncertain in 24 CONCLUSION: Although there was little disagreement amongst an expert panel of IBD physicians and surgeons, there remained uncertainty about the use of medical and surgical therapy in nearly one third of situations in patients with mild-moderate UC. These results could be used to guide the design of clinical trials for these patient groups in order to guide best practice.

Maneuvering Clinical Pathways for Ulcerative Colitis.

Recent years have brought about several advances in the treatment of patients with ulcerative colitis (UC). Here, we discuss salient recommendations of recent treatment guidelines; review the efficacy, safety, and real-world data of vedolizumab and tofacitinib; appraise their place vis-à-vis established agents; and consider the newly proposed approaches of risk-stratified and treat-to-target therapy. Once daily oral mesalamine dosing is equivalent to split dosing in mild-moderate UC. Real-world data are accumulating on the effectiveness and safety of vedolizumab for moderate to severe UC, while there are few such data on the most recently approved agent, tofacitinib. High-dose infliximab is being investigated for severe UC. New approaches are challenging the established paradigm of selecting therapy based on current disease activity. The risk-stratified approach incorporates long-term risk as well as the current burden of inflammation. The treat-to-target approach aims at improved long-term outcomes by adjusting therapy to resolve intestinal inflammation. The therapeutic options for UC are continually expanding. Risk-stratified therapy and the treat-to-target approach represent paradigm shifts in UC management. Optimal disease control requires an individualized approach that takes into consideration current inflammatory burden, long-term risk, patient preferences, and ongoing assessment of response to treatment.

Safety and Efficacy of Heterologous FMT by SQIMC-md Capsule in Mild-moderate Ulcerative Colitis Patients

Safety and Efficacy of Heterologous FMT by SQIMC-md Capsule in Mild-moderate Ulcerative Colitis Patients