Months For Ulcerative Colitis Research Articles

Diagnostic delay in inflammatory bowel diseases in children

Introduction. The incidence and prevalence of inflammatory bowel disease (IBD) in children is increasing steadily. The diagnosis is often delayed that can lead to an increased risk of complications and significantly decrease the quality of life in the child. The identification of reasons associated with prolonged diagnostics must bring down healthcare costs, reduce the frequency of surgical interventions and use of biological agents. The aim of our study was to determine the duration of diagnosis and associated factors in IBD children.
 Materials and methods. The research held at the National Medical Research Center for Children’s Health included the analysis of three hundred sixty four medical records of children diagnosed with ulcerative colitis (UC) or Crohn’s Disease (CD). This investigation assessed the time of onset of the first symptoms, the first visit to a doctor, the time of establishing the diagnosis, and the first symptoms. The diagnostic time and delay for all IBD were determined. 
 Results. The study included 286 patients, including 157 CD and 129 UC. The diagnostic delay was 18 months for CD, and 6 months for UC. The manifestation of the disease with extraintestinal symptoms in CD was found to increase the chance of a diagnosis duration of more than 18 months by 8.88 times (95% CI 3.4–23.06, p < 0.001), and in UC — more than 6 months by 4.98 times (95% CI 1.52–16.3, p = 0.009). Moreover, the absence of liquid stools, blood in the stool, low-grade fever, and abdominal pain in CD can lead to an increase in diagnostic time. It was also found that UC boys are diagnosed much longer. 
 Conclusion. CD requires more time to make a diagnosis than UC, which is due to the peculiarity of the clinical course of the di­sease. Despite the fact that a doctor has consulted patients in time, a delay in establishing a diagnosis occurred at the examination stage, so that requires additional alertness from the specialist’s side.

A Multicentre Study of the Clinical and Epidemiological Profile of Inflammatory Bowel Disease in Northeast Brazil.

Ulcerative colitis (UC) and Crohn's disease (CD) are inflammatory bowel diseases (IBDs) with multifactorial causes. They are becoming more prevalent in developing countries such as Brazil; however, relevant studies in poorer regions of the country are limited. Here, we report the clinical-epidemiological profile of patients with IBD treated at reference centers in three states of Northeast Brazil. This was a prospective cohort study involving patients at referral outpatient clinics for IBD from January 2020 through December 2021. Of 571 patients with IBD, 355 (62%) had UC, and 216 (38%) had CD. The patients were predominantly women (355, 62%) for both UC and CD. Extensive colitis was the pattern present in 39% of the UC cases. For CD, ileocolonic disease was the predominant manifestation (38%), with 67% of cases showing penetrating and/or stenosing behavior. The majority of patients were diagnosed between the ages of 17 and 40, corresponding to 60.2% in CD and 52.7% in UC. The median time between symptom onset and diagnosis was 12 months for CD and 8 months for UC (p=0.042). Joint involvement was the most frequent extraintestinal manifestation, with arthralgia and arthritis present in 41.9% and 18.6% of the patients, respectively. Biological therapy was prescribed to 73% of CD patients and 26% of UC patients. A progressive increase in new cases was observed in every 5-year interval over the last five decades, with 58.6% being diagnosed in the last 10 years. More extensive disease behavior patterns predominated in UC, while forms associated with complications were prevalent in CD. A prolonged time to diagnosis may have contributed to these findings. A progressive increase in IBD incidence was observed and may be related to greater urbanization and better access to specialized outpatient clinics, resulting in improvements in diagnosis.

Effect of Breastfeeding on the Risk of Developing Inflammatory Bowel Disease

Aim: This study aimed to investigate whether breastfeeding in early childhood affect the risk of devoloping inflammatory bowel disease (IBD).
 Materials and Methods: The data of patients obtained from the survey were compared to the data of their non-IBD siblings as a control group. The relationship between the demographic and clinical chararecteristics of IBD patients and breastfeeding was also analyzed. 
 Results: 304 IBD patients were included in the study. 182 (59.9%) of the patients were diagnosed with ulcerative colitis (UC), and 122 (40.1%) with Crohn’s disease (CD). The CD patients included in the study were compared to the CD siblings group of 332, and the UC patients compared with the UC siblings group of 508. Compared to the control groups, the proportion of those who never breastfed was higher in both the CD and UC groups (7.4% vs. 2.1% for CD [p=0.017] and 3.9% vs. 0.8% for UC [p=0.01]), and the risk of disease increased in those who was not breastfed (OR= 3.70 [1.35-10.16] for CD [p=0.017] and OR= 5.07 for UC [1.47-17.53] [p=0.010]). The protective effect against CD increased as the duration of breastfeeding increased, but that the protection increased with breastfeeding for up to 12 months for UC, and breastfeeding for more than 12 months did not provide additional protection. There was no relationship between breastfeeding and demographic and behavioral chracteristics of patients
 Conclusions: Not having been breastfed in infancy increases the risk of developing both UC and CD, and as the duration of breastfeeding increases, the protection against diseases risk increases.

Clinical and Demographic Features and Treatment Approaches for Inflammatory Bowel Diseases (Crohn’s Disease, Ulcerative Colitis) in the Russia. The Primery Results of the Analysis of the National Register

The National Registry of Patients with Inflammatory Bowel Disease (IBD) in the Russian Federation was established to study the epidemiological and clinical characteristics of patients and evaluate the actual clinical practice of medical and surgical treatment.AIM: to analyze the data of patients with IBD in the Russian Federation including clinical and demographic characteristics, medical status of patients, the frequency of use of various classes of drugs and response to treatment, the survival rates of advanced therapy drugs and the reasons for their cancellation.METHODS: from May 2017 to August 2021, depersonalized data of 3827 adult patients with IBD (ulcerative colitis (UC) – 2358 pts, Crohn's disease (CD) - 1469 pts) from 80 regions of the Russian Federation were included in the registry, both with previously and newly diagnosed UCor CD, who are in inpatient or outpatient care.RESULTS: in our population, the ratio of UC: CD was 1.6:1. The distribution of patients by sex was the same. The average age of patients in the registry was 40.6±13.1 (13-83 years) for UC and 38.5±14.3 (15-75 years) for CD, the half of patients were in the age range of 21-40 years for both diseases. The average age of disease onset did not differ for UC and CD and was 35.3 year (12-75 years) and 31.2 year (14-72 years) respectively. The duration between the onset of symptoms and the establishment of a diagnosis was 13.2 months in UC, and statistically significantly longer in CD - 34.8 months (P<0.01). The proportion of smokers in CD patients was statistically significantly higher than in UC ones (14.6% versus 9.6%, respectively, P<0.001). The incidence of disability was also significantly higher in CD than in UC patients (41.7% vs. 29.8%, P<0.01). The diagnosis of mild UC was established in 36% of cases, moderate UC occurred in 48.9% of patients, severe UC in 14.2% of patients. For the first time, the frequency of acute severe UC (1%) was estimated. The majority of patients had total UC (56.8%), 33% had left-side colitis, and 9.4% had proctitis. CD was divided by localization into ileocolitis 55.9%, terminal ileitis 23.9%, colitis 20.2%, perianal lesions were noted in 32.5% of cases. The overall complication rate in CD was 46% (681 patients), of which the most common were strictures - 48% and fistulas- 25.1%.Frequencyof extra intestinal manifestations did not differ in UC and CD patients and was 20.1% (473 patients) and 24.5% (360 patients), respectively. Of these, musculoskeletal lesions were more common (41.6% in UC, 42% in CD), lesions of the skin, eyes, mucous membranes, liver, anemia were also noted. In the treatment of IBD, steroids were used most often (79.3% and 65% in UC and CD, respectively), followed by 5-ASA - 47% in UC, 32.4% in CD. Immunosuppressant’s in CD were prescribed significantly more often (28.4%) than in UC (11%) (p<0.05). Biologics were used in 20.6% of UC patients and in 30% of CD patients. The highest 2-year survival of advanced therapy was noted for ustekinumab in CD (96%), for tofacitinib in UC (89.3%), and for vedolizumab in both UC and CD (92.5% and 88.4% respectively). The survival rates of all TNF-α inhibitors were approximately the same and varied within 58.1-72.4% in UC and 60-70% in CD. The most common reasons for discontinuation of advanced treatment were lack of efficacy/loss of response in both UC and CD. The second common reason was achieving remission. Certolizumab pegol in CD was canceled for this reason most often- 22.7% of cases. A small number of patients discontinued treatment due to adverse events: for UC - 1 patient each on adalimumab, golimumab, and tofacitinib, and 7 patients on infliximab, for CD- 5 patients on infliximab and adalimumab (9.6% and 7.5%, respectively) and 2 patients (4.6%) on certolizumab. Unfortunately, the proportion of discontinuation for non-medical reasons was significant and varied from 7% to 50% for different drugs. In some patients, the reason for discontinuation of therapy remained unknown.CONCLUSION: The difficulties of differential, often untimely diagnosis of CD and UC, the predominance of complicated and severe forms against the background of an increase in morbidity and prevalence, and at the same time the lack of adequate statistical accounting of CD and UC, make it necessary to create a unified clinical register of patients with IBD. The register of IBD patients will provide a holistic picture of the IBD situation in the country, including optimizing the use of budget funds for the treatment of patients with CD and UC, ensuring their rational planning.

P269 Predicting IBD years before diagnosis using routine blood tests

Abstract Background Recent studies such as the GEM project have identified microbial, serological and metabolomic markers that may help predict inflammatory bowel disease (IBD) well in advance of diagnosis, with the ultimate goal of pre-disease prevention. In this population-based study, we used the epi-Israeli IBD Research Nucleus (IIRN) validated cohort to explore the utility of routine blood tests as markers for pre-diagnostic IBD prediction. Methods We included all blood tests from all IBD patients diagnosed from 2005-2020 insured in three of the four Israeli health maintenance organizations (HMOs), and individually matched each to two non-IBD controls. Test results were collected and collated by number of months pre-diagnosis, then reported over time until diagnosis. Means were compared using Welch's t-test with false discovery rate correction to account for multiple comparisons. Trends over time were analyzed to detect tests that showed divergence between cases and controls at least one year before diagnosis. Results Pre-diagnosis results from 142 different blood tests were collected for 7,630 Crohn’s disease (CD) patients and 6,026 ulcerative colitis (UC) patients (mean age 33.3±17.4 years for CD and 38 ± 17.9 years for UC). Median duration of pre-diagnosis data collection was 50 (IQR 11-96) months for CD and 48 (IQR11-96) months for UC. Of the 142 tests, 24 (17%) showed significant differences between CD and controls at least one year pre-diagnosis (Figure 1); these included not only inflammation-related tests such as ESR, hemoglobin and albumin, but also seemingly unrelated tests such as bilirubin, cholesterol and creatinine. In UC patients, no tests showed statistically significant differences at least one year pre-diagnosis. Conclusion We were able to detect changes in blood tests collected as part of routine care long before CD diagnosis, opening the possibility of detecting early signals of future CD in patients undergoing routine blood tests. These may be used for developing screening and prediction models for prevention strategies. This research was partially supported by the Israeli Council for Higher Education (CHE) via the Data Science Research Center, Ben-Gurion University of the Negev, Israel. The epi-IIRN project has been funded by an educational grant from the Leona M. and Harry B. Helmsley Charitable Trust.

The Influence of the Introduction of Biologic Agents on Surgical Intervention in Paediatric Inflammatory Bowel Disease

To determine how the use of biological therapy is associated with surgical intervention for paediatric inflammatory bowel disease (PIBD) at a population level. Hospital Episode Statistics data were obtained for all admissions within England (1997-2015), in children aged 0-18 years, with an ICD-10 code for diagnosis of Crohn disease (CD), ulcerative colitis (UC), or inflammatory bowel disease-unclassified (IBD-U). Office of Population Censuses and Surveys Classification of Surgical Operations and Procedures codes for major surgical resection associated with PIBD and for biological therapy were also obtained. Data are presented as median values (interquartile range). In total, 22,645 children had a diagnosis of PIBD of which 13,722 (61%) had CD, 7604 (34%) had UC, and 1319 (5.8%) cases had IBD-U. Biological therapy was used in 4054 (17.9%) cases. Surgical resection was undertaken in 3212 (14%) cases, more commonly for CD than UC (17.5 vs 10.3%, P < 0.0001). Time from diagnosis to major surgical resection was 8.3 (1.2-28.2) months in CD and 8.2 (0.8-21.3) months in UC. As the time-frame of the dataset progressed, there was a decreased rate of surgical intervention ( P = 0.04) and an increased use of biological therapy ( P < 0.0001). Additionally, the number of new diagnoses of PIBD increased. The introduction of biologic agents has been associated with a reduction in cases undergoing surgery in children with a known diagnosis of PIBD. As time progresses we will be able to determine whether biological therapies prevent the need for surgery altogether or just delay this until adulthood.

Epidemiological trends of pediatric IBD in Italy: A 10-year analysis of the Italian society of pediatric gastroenterology, hepatology and nutrition registry.

The present study aimed at evaluating Italian epidemiological trends of pediatric inflammatory bowel diseases (IBD) over the period 2009-2018. Data from 1969 patients enrolled in the Italian Society of Pediatric Gastroenterology, Hepatology and Nutrition Registry, by 49 pediatric IBD centers throughout the country, were analyzed, comparing three different time intervals (2009-2012, 2013-2015, 2016-2018). The number of new IBD diagnoses ranged from 175 to 219 per year, evenly distributed over the examined period of time. From 2009 to 2018, the minimal incidence ranged from 1.59 to 2.04 /105 inhabitants aged < 18 years, with an overall slight predominance of ulcerative colitis (UC) over Crohn's disease (CD) (ratio: 1.1). Mean diagnostic delay was 6.8 months for CD and 4.1 months for UC, with a significant reduction for CD when comparing the three-time intervals (p=0.008). The most frequent disease locations according to the Paris classification were ileocolonic for CD (41.3%) and pancolitis for UC (54.6%). The minimal incidence rate in Italy seems to have stabilized over the last two decades, even if it has increased when compared to previous reports. UC is still slightly more prevalent than CD in our country. Diagnostic delay significantly decreased for CD, reflecting an improved diagnostic capacity.

P208 Enthesopathies in patients with inflammatory bowel diseases

Abstract Background Background. The aim of study was to evaluate the enthesis in patients with inflammatory bowel diseases (IBD) and to assess the involvement of enthesis in different IBD behavior. Methods Methods. 95 IBD pts were prospectively enrolled into the study: 55 pts with ulcerative colitis (UC) and 40 - with Crohn’s disease (CD). The average duration of the disease was 48 (12; 102) months in UC, and 42 (18; 87) months in CD. The severity of UC exacerbation was assessed by the Mayo index, in CD – by Harvey-Bradshaw index. In UC, moderate and severe exacerbation was revealed in 40 pts (73%), in CD - in 17 (43%). Among 95 pts with IBD, extraintestinal manifestations occurred in 67 pts (71%), of which 34 (62%) pts with UC and 33 (82%) pts with CD. 70 enthesis were evaluated clinically and by US in each pt. The clinical examination included tenderness of enthesis, US examination with power Doppler detected inflammatory (hypoechogenicity of enthesis, thickening of enthesis, presence of vascularization) and structural (erosion, enthesophyte) changes in enthesis. Fisher’s exact test, Spearman’s coefficient and binary logistic regression to determine the odds ratio (OR) were used to calculate differences. Results Results. The duration of IBD course directly correlated with the number of tender entheses (SR = 0.24; p = 0.017), as well as the number of enthesophytes (SR = 0.20; p = 0.044). The severity of IBD exacerbation and enthesis involvement didn’t have statistically significant correlation. However, the inflammatory lesions of entheses (the number of erosions with vascularization) correlated with CRP level (SR = 0.25; p = 0.01). We also identified a relationship between the presence of extraintestinal manifestations and the enthesis involvement: for example, the presence of at least one extraintestinal manifestation increased the likelihood of detecting erosions by 4.77 times (95% CI 1.6–13.9, p = 0.003). The presence of joint pain increased the likelihood of detecting erosions of entheses by 3.37 times (95% CI 1.18–9.65, p = 0.02). Clinical signs of musculoskeletal system involvement (tenderness of enthesises on palpation) significantly increased the frequency of enthesitis, including vascularized enthesitis (p = 0.01). Conclusion Conclusion. In IBD pts with long disease duration and the presence of extraintestinal manifestations, structural (erosion, enthesophytes) changes in enthesis were observed significantly more often. The frequency of entheses erosions was higher in the presence of pain in the joints, and the number of erosions with vascularization with an increase in laboratory markers of inflammation (CRP).

P314 TNF gene activation used as criterion to discontinue biologic therapy – A patient series introducing the NovaPrime TNF kit

Abstract Background Severe inflammatory bowel disease can be successfully treated with biologic drugs such as anti-TNF. However, there is no consensus on if and how to stop treatment. Our group has earlier shown that normalization of TNF gene expression may be a beneficial prognostic factor when attempting to discontinue biologic therapy. We here present data from a series of patients in endoscopic remission and with normalized TNF gene expression. Methods Severe inflammatory bowel disease can be successfully treated with biologic drugs such as anti-TNF. However, there is no consensus on if and how to stop treatment. Our group has earlier shown that normalization of TNF gene expression may be a beneficial prognostic factor when attempting to discontinue biologic therapy. We here present data from a series of patients in endoscopic remission and with normalized TNF gene expression. A total of 91 patients were recruited at hospitals in Norway and Italy: 55 patients (32 UC, 23 CD) in remission (picked by normalization of TNF using our in-house TNF qPCR), and for comparison: 14 patients with active disease, and 22 normal controls. Mucosal samples taken prior to drug discontinuation from all patients were re-measured for TNF mRNA by the NovaPrime TNF kit. Results A clear difference could be seen between normal controls and patients with active disease, showing highly elevated TNF mRNA values in the active disease group. The patients in remission had values resembling the normal controls with values generally below a cut-off of 9060 copies/µg total RNA by the NovaPrime TNF kit. The patients in remission were followed for up to 5 years noting two endpoints: relapse triggering any adjustment of medication, and relapse triggering restart of biologics. Median survival time before adjusting medication was 12 months for ulcerative colitis and 17 months for Crohn’s disease. Median time to restart of biologics was 21 months (2 – 40) overall, and after 3 years 43% still were not in need of biologic therapy. Conclusion We conclude that the NovaPrime TNF kit yields consistent readings comparable to our in-house assay, and that this industrial standard kit enables any PCR lab to perform TNF gene expression in samples from intestinal mucosa. A considerable proportion of patients with normalized TNF gene expression can maintain long term remission without biologic therapy, relieving health care costs and potential side effects of long-term therapy.

Clinical experiences and predictors of success of treatment with vedolizumab in IBD patients: a cohort study

BackgroundVedolizumab has become a standard treatment for the inflammatory bowel diseases ulcerative colitis (UC) and Crohn’s disease (CD). However, there is an ongoing debate on the ideal individual treatment algorithms and means to predict treatment response are not routinely established.AimsWe aimed to describe our experiences with vedolizumab at a large German tertiary referral center and to identify clinical predictors of success of vedolizumab treatment.MethodsWe performed a retrospective single-center cohort study employing univariable and multivariable analyses as well as Kaplan–Meier analyses of persistence on treatment.Results36% and 35% of the patients with UC and CD, respectively, reached clinical remission after 17 weeks. Patients with lower clinical disease activity were more likely to achieve remission. The median persistence on treatment was 33 months for UC and 29 months for CD.ConclusionOur study confirms that vedolizumab is an efficient option for the treatment of UC and CD. Clinical parameters of disease activity may help to predict the success of treatment.

Epidemiología y comportamiento de la enfermedad inflamatoria intestinal en la población ecuatoriana

In Ecuador, there are no epidemiological data on inflammatory bowel disease (IBD). We seek to determine the epidemiology and behavior of IBD in the Ecuadorian population. Methods. Descriptive observational study, using the clinical records of patients diagnosed with IBD, from the three referral centers for IBD of Ecuadorian social insurance, from 1990 to 2018. Results. This study included a total of 206 patients diagnosed with IBD, of these, 148 with ulcerative colitis (UC) and 58 with Crohn’s disease (CD). The average age of diagnosis for both UC and CD was 42 years. The average time from the onset of symptoms to the diagnosis was 7.5 months for UC and 11.6 months for CD. The most frequent symptom in UC was digestive bleeding (62.2%) and chronic diarrhea in CD (37.2%). The most frequent extension in UC was extensive colitis (41%). The most frequent location in CD was ilecolonic (36%). The predominant extra digestive manifestation for both was articular, UC (64%) and CD (70%). The predominant treatment in UC and CD was 5ASA in 40% and 54% respectively. In CD, the diagnostic time longer than 12 months was associated with the need for surgery (p = 0.03). The prevalence of IBD in Ecuador is 5.2 per 100,000 inhabitants, corresponding 3.7 to CU and 1.5 to CD. Conclusions. IBD in Ecuador presents a comparable increase to that reported in other countries that were also considered low risk.

P173 Very–Early-Onset inflammatory bowel disease: Russian single centre experience

Abstract Background The incidence of very early-onset inflammatory bowel disease (VEOIBD) is on the rise in Russia but the clinical data is lacking. We aim to study the disease phenotype, clinical course and the presence of primary immunodeficiency (PID) patients in this group. Methods Clinical records of VEOIBD patients treated in Russian State Pediatric Hospital between 2000 and 2018 were revised. In 60 patients admitted between 2016 and 2018 targeted sequencing (PID panel) was performed. 10 patients received genetic testing previously. Results 135 VEOIBD patients were identified: 95 (70%)with ulcerative colitis (UC), 31 (23%) with Crohn’s disease, 9 (7%) with PID. In 14 (11%) IBD patients the diagnosis was changed from UC to CD and vice versa. Median time of diagnosis was 7 months in UC, 24 months in CD and 44 months in PID. The most common clinical symptoms were loose stools (UC—98%, CD—84%), bloody stools (UC—93, CD—65%), stomach ache (UC—53%, CD—52%), fever (UC—35%, CD—42%). Common laboratory features included anemia (UC—56%, CD—39%), low serum ferrum level (UC—75%, CD—61%), thrombocytosis (UC—53%, CD—45%). From 103 patients tested for ANCA 26% had positive results (24—UC, 3—CD). Mean calprotectin level (76 patients) was 750 ± 54.4 μg/g. Pancolitis was seen in UC (84%), as well as in CD (61%). Epithelioid granulomas in CD were present in 7 patients, in 5 of them they were detected years after initial diagnosis. Sixty-nine% of UC and 90% of CD patients received steroids as induction therapy, steroid-dependency was common (42% in UC and 55% in CD). Forty-nine% of patients with UC and 23% od CD patients received azathioprine, anti-TNF agents were used in 26% UC patients and 77% CD patients. In 35% of patients receiving anti-TNF biologic therapy was started before the age of 6 years. 23,8% of VEOIBD patients failed to achieve clinical remission. Total colectomy was performed in 11 patients, in 3 of them the diagnosis was subsequently changed to CD. Segmental resection was performed in 9 CD patients, in 3 of them while on therapy. The most common form of PID was XIAP deficiency (3 patients), 2 of them achieved endoscopic remission after allogenic stem cell transplantation. Conclusion In the VEOIBD group CD resembles UC clinically and endoscopically. A substantial number of patients requires immunosuppressive and biologic therapy before the age of 6 years. Colectomy rates are still high regardless the use of biologics. Boys with refractory VEOIBD should be screened for XIAP deficiency.

P574 Incidence and indicators of suboptimal response to tumour necrosis factor antagonist therapy in Chinese patients with inflammatory bowel disease: Results from the EXPLORE study

Abstract Background Inflammatory bowel disease (IBD) patients may experience a suboptimal response to anti-tumour necrosis factor (TNF) therapy. In China, these data are limited. The EXPLORE study aimed to assess the incidence and indicators of suboptimal response to first-line anti-TNF agents in IBD patients in real-world practice in the newly industrialised countries. Methods The EXPLORE study was a multinational, retrospective chart review study. In the China subgroup, adult patients from 10 centres diagnosed with ulcerative colitis (UC) or Crohn’s disease (CD) and who initiated first anti-TNF treatment between March 2010 and March 2015, were included. The cumulative incidence (CI) of suboptimal response was assessed over 24 months since the anti-TNF initiation. The indicators of suboptimal response included: IBD-related hospitalisation, dose-escalation, discontinuation including switch to another anti-TNF, non-biologic therapy augmentation, or IBD-related surgery. Primary non-response (PNR) and secondary loss of response (SLOR) were defined as any suboptimal response indicator at &amp;lt;4 and ≥4 months after anti-TNF initiation, respectively. Results Overall, 287 first-line anti-TNF treated patients (35 UC; 252 CD) were included: male, UC 54.3% (n = 19), CD 74.6% (n = 188); mean (SD) age (years), UC 43.1 (14.2), CD 31.9 (11.3); median (min-max) disease duration (years), UC 1.0 (0–9), CD &amp;lt;1 year (0–21); median (min-max) follow-up (months), UC 27.6 (24–60), CD 40.0 (24–60). At 12 and 24 months, the CI of suboptimal response to first anti-TNF treatment was 51.4% and 75.7% in UC, 45.4% and 57.0% in CD, respectively (Figure 1). The median time to the first suboptimal response was 7.2 months in UC and 14.3 months in CD. The CI of PNR was 31.2% in UC and 33.7% in CD. The CI of SLOR was 29.4% and 64.7% in UC, 17.7% and 35.2% in CD at 12 and 24 months, respectively. The most frequent first suboptimal response indicator was ‘discontinuation of anti-TNF therapy’ in UC patients (56.3%) while for CD patients it was ‘IBD-related hospitalisation’ (56.1%) followed by ‘augmentation with non-biological therapy’ in both cohorts (UC 31.3%; CD 22.8%). Conclusion Approximately three-quarters of UC and over half of CD patients experienced a suboptimal response to their first anti-TNF agent at 24 months. Given the high unmet needs observed with anti-TNF therapies in China, IBD patients may benefit from greater optimisation of care and new biologic options.

P181 Triage straight to test (tSTT) improves early diagnosis of inflammatory bowel disease (IBD)

Abstract Background It is well known that there is a significant delay in diagnosing IBD. On average it takes 4–9 months to diagnose Crohn’s disease (CD) and 4 months for ulcerative colitis (UC)1. Barts Health NHS Trust in the UK is one of the pioneer hospitals in establishing Triage Straight to Test (tSTT) for patients with lower gastrointestinal (GI) symptoms. The aim of the programme is to reduce the time from a primary care physician (General practitioner) referral to the secondary care to achieve a definitive diagnosis. This minimises the number of outpatient appointments required and makes an efficient use of medical and surgical resources. We aim to study whether tSTT pathway reduces the time to diagnose IBD. Methods Patients with lower GI symptoms were referred to a specialist tSTT triage nurse, where they were allocated into two pathways—routine (18-week wait) and upgraded (2-week wait). A comprehensive telephone assessment, calprotectin levels and clinical information provided by the GP would determine the route and urgency of the investigation. Pathologies such as cancer, IBD and polyps were treated via a predefined management pathway. The patients with a benign disease were discharged and in some cases called for a follow-up appointment. Results During July 2013 to November 2019 a total of 2270 patients have been triaged. One hundred and one (4.45%) patients were diagnosed with IBD, where 36 patients (36%) were histologically characterised as CD and the other 65 patients (64%) were diagnosed as UC. The mean age of diagnosis for both CD and UC patients was 40 years (range 16–79). The average time from referral to endoscopy on tSTT pathway was 22.6 days for upgraded referrals and 43.5 days for non-upgraded. There is a significant difference in time to diagnosis between routine and upgraded pathways (22.6 days vs. 43.5 days, p &amp;lt; 0.001). Conclusion The above data suggest a significant reduction in time to diagnose IBD through tSTT pathway. Early diagnosis ensures that the patient receives an early customised care and avoids disease-related complications. It also means that the NHS resources can be used wisely by avoiding a delay in getting outpatient consultant appointments.

THE ONSET OF CLINICAL MANIFESTATIONS IN INFLAMMATORY BOWEL DISEASE PATIENTS.

The diagnosis of inflammatory bowel disease is often delayed because of the lack of an ability to recognize its major clinical manifestations. Our study aimed to describe the onset of clinical manifestations in inflammatory bowel disease patients. A cross-sectional study. Investigators obtained data from interviews and the medical records of inflammatory bowel disease patients from a reference centre located in Brazil. A total of 306 patients were included. The mean time between onset of symptoms and diagnosis was 28 months for Crohn's disease and 19 months for ulcerative colitis. The main clinical manifestations in Crohn's disease patients were weight loss, abdominal pain, diarrhoea and asthenia. The most relevant symptoms in ulcerative colitis patients were blood in the stool, faecal urgency, diarrhoea, mucus in the stool, weight loss, abdominal pain and asthenia. It was observed that weight loss, abdominal pain and distension, asthenia, appetite loss, anaemia, insomnia, fever, nausea, perianal disease, extraintestinal manifestation, oral thrush, vomiting and abdominal mass were more frequent in Crohn's patients than in ulcerative colitis patients. The frequencies of urgency, faecal incontinence, faeces with mucus and blood, tenesmus and constipation were higher in ulcerative colitis patients than in Crohn's disease patients. The mean time from the onset of clinical symptoms to the diagnosis of Crohn's disease was 37 months for patients with ileocolonic location, 26 months for patients with ileum location and 18 months for patients with colon location. In ulcerative colitis patients, the mean time from the onset of symptoms to diagnosis was 52 months for proctitis, 12 months for left-sided colitis and 12 months for extensive colitis. Ulcerative colitis presented a high frequency of intestinal symptoms, and Crohn's disease showed a high frequency of systemic manifestations at the onset of manifestation. There was a long delay in diagnosis, but individuals with more extensive disease and more obvious symptoms showed a shorter delay.

Efficacy, Safety and Mucosal Healing of Methotrexate in a Large Longitudinal Cohort of Inflammatory Bowel Disease Patients

Background/Aims: Evidence for the effectiveness of methotrexate (MTX) in treating inflammatory bowel disease (IBD) is still incomplete. This study assessed the effectiveness, safety and mucosal healing in IBD patients treated with MTX in the Swiss IBD Cohort. Methods: Efficacy was defined by physician assessment or by CD activity index <150 points for Crohn’s disease (CD) or Modified Truelove and Witts activity index <4 points for ulcerative colitis (UC), measured at least after 3 months of MTX therapy. Mucosal healing was evaluated after 3 months or more of therapy. Results: MTX was administered to 341 patients (262 CD; 79 UC) out of 2,660 patients. MTX effectiveness was 59.5% (128/215) in CD and 40.0% (24/60) in UC (chi² = 7.2409, p = 0.007). Among patients on MTX therapy at the time of analysis, remission was obtained in 87.4% (76/87) and 69.2% (9/13) for CD and UC patients respectively. The median duration of MTX therapy was 40 months for CD and 15 months for UC. Occurrence of adverse events was the first reason for treatment discontinuation (39.4% of all cases). The rate of mucosal healing with MTX was 9.5% for CD and 25% for UC patients respectively. Conclusion: MTX therapy was effective for the induction and maintenance therapy in IBD patients, with only a modest mucosal healing ability.

Indicators of suboptimal tumor necrosis factor antagonist therapy in inflammatory bowel disease

BackgroundInflammatory bowel disease (IBD) is refractory to treatment in one-half of patients. AimsTo evaluate the occurrence of suboptimal therapy among patients with IBD treated with tumor necrosis factor antagonists (anti-TNFs). MethodsA multinational chart review in Europe and Canada was conducted among IBD patients diagnosed with ulcerative colitis (UC) or Crohn’s disease (CD) who initiated anti-TNF therapy between 2009 and 2013. The primary endpoint was the cumulative incidence of suboptimal therapy during a two-year follow-up period, defined by the presence of the following indicators: dose escalation, discontinuation, switching, non-biologic therapy escalation, or surgery. ResultsThe study included 1195 anti-TNF initiators (538 UC and 657 CD). The majority of patients (64% of UC and 58% of CD) had at least one indicator of suboptimal therapy. The median time to suboptimal therapy indicator was 12.5 and 17.5 months for UC and CD patients, respectively. Among the 111 UC and 174 CD anti-TNF switchers, 51% and 56% had an indicator of suboptimal therapy, respectively. The median time to suboptimal therapy indicator with the second anti-TNF was 14.3 and 13.0 months for UC and CD patients, respectively. ConclusionThe majority of IBD patients showed suboptimal therapy with current anti-TNFs.

Vedolizumab provides clinical benefit over 1 year in patients with active inflammatory bowel disease - a prospective multicenter observational study.

Vedolizumab, a monoclonal antibody targeting the α4β7-integrin, is effective in inducing and maintaining clinical remission in Crohn's disease and ulcerative colitis according to randomised clinical trials. To determine the long-term effectiveness of vedolizumab in a real-world clinical setting. This observational registry assessed the clinical outcome in patients treated with vedolizumab for clinically active Crohn's disease (n = 67) or ulcerative colitis (n = 60). Primary endpoint was clinical remission (HBI ≤ 4/pMayo ≤ 1) at week 54. Secondary endpoints included clinical response rates (HBI/pMayo score drop ≥3) and steroid-free clinical remission at weeks 30 and 54. Vedolizumab was stopped in 69/127 (56%) patients after a median time of 18 weeks (range 2-49) predominantly owing to lack or loss of response. Using nonresponder imputation analysis, clinical remission and steroid-free remission rates were 21% and 15% in Crohn's disease and 25% and 22% in ulcerative colitis, respectively. Lack of clinical remission was associated with prior treatment with anti-TNF or with steroids for more than 3 months in the last 6 months in ulcerative colitis. At week 14, the absence of remission in Crohn's disease or nonresponse in ulcerative colitis indicated a low likelihood of clinical remission at week 54 [2/31 (7%) in Crohn's disease, 4/41 (10%) in ulcerative colitis]. Accordingly, declining C-reactive protein in inflammatory bowel disease and/or lower faecal calprotectin in ulcerative colitis at week 14 predicted remission at week 54. Among patients who started vedolizumab for active inflammatory bowel disease, clinical remission rates are 21-25% after 54 weeks.

6-Mercaptopurine for Azathioprine Intolerant Inflammatory Bowel Disease: Literature Search and Reappraisal of Own Data.

Thiopurines have been shown to effectively maintain remission of both Crohn's disease (CD) and ulcerative colitis (UC), and to behave as disease modifiers if used for >12 months in UC. Gastric intolerance manifesting as nausea constitutes a demanding drawback of thiopurines, at times forcing treatment discontinuance. A few studies have now indicated that some patients might tolerate mercaptopurine (6-MP) for azathioprine. In this paper, we review the literature, and reappraise our own data against the published figures. The data which form the basis for this study span over all visit reports that were released between January 2008 and December 2011 in a primary care Hospital, in Turin, Italy. For the aim of this study we searched our own database and the MedLine using the key-words "azathioprine", "mercaptopurine", "thiopurine", "inflammatory bowel disease", "Crohn's disease", "ulcerative colitis". We retrieved 85 azathioprine prescriptions for 42 UC, 37 CD, and 6 miscellaneous patients. There were 10 episodes of gastric intolerance to azathioprine, which were switched to 6-MP: 6 out of 10 (60%) responded and tolerated the switch drug in a median follow-up of 66 months. Female gender prevailed (p=0.038) in the azathioprine intolerant subset. A trial with 6-MP is worth being offered to azathioprine intolerant inflammatory bowel disease subjects at any center matching the standard figures of specific performance.

Vedolizumab Therapy in Crohnʼs Disease and Ulcerative Colitis: A Retrospective Review of Post-procedural Complications

Introduction: Vedolizumab (VDZ) was approved for the treatment of moderate to severe ulcerative colitis (UC) and Crohn's disease (CD) in May 2014. This case series reviews the occurrence of any post-procedure complications after initiation of VDZ therapy in 73 patients seen at a large tertiary referral center. Methods: Retrospective chart review of patients on VDZ therapy from June 2014 to May 2015. Data collected included age, sex, smoking status, disease phenotype, disease distribution, and all endoscopic and surgical procedures after initiation of VDZ. Body mass index (BMI), serum albumin, duration of VDZ therapy and pre-procedure timing of VDZ dosing was recorded for patients who had a procedure. Post-procedural complications were scored using the Accordion Classification scale, a validated tool to grade the severity of post-operative complications. Results: 73 patients were identified: 35 male/38 female, 45 CD/28 UC, 55/73 had never smoked, 4/73 were current smokers, and 14/73 were former smokers. 32/45 Crohn's patients had both large and small bowel disease. 21/45 Crohn's patients had perirectal involvement. Mean duration of VDZ therapy in the study period was 5.5 (SD ± 2.27) months in CD and 6.5 (SD ± 2.28) months in UC. 46 procedures occurred in 36 patients after initiation of VDZ therapy (Table 1). 5 procedures had associated complications, including spontaneous mucosal tearing, anastomotic leak with intra-abdominal abscess, and wound dehiscence. In these patients, the mean duration of VDZ therapy prior to procedure was 5 (SD ± 1.59) months, mean number of days between VDZ infusion and procedure was 29 (SD ± 19.59) days, mean BMI was 24 (SD ± 6.61) kg/m2 and mean albumin was 3.4 (SD ± 0.38) g/dL (Table 2).Table 1: Demographics of all VDZ therapy patientsTable 2: Characteristics of Patients with ComplicationsConclusion: VDZ affects leukocyte trafficking to the intestines and therefore has a theoretically increased risk of impaired intestinal mucosal and serosal wound healing due to a reduction in the inflammatory response needed to initiate the healing of these injuries. While initial phase III trials in UC and CD did not show a significantly increased risk of bowel perforation, an open-label trial is ongoing to better characterize the long-term safety of VDZ. This is the first case series review of non-study patients on VDZ therapy to evaluate the occurrence of these potential complications. Further studies are needed to better characterize if VDZ therapy has any impact on the occurrence and severity of post-procedural complications.