bluuebunny/crossref_metadata_2025 huggingface dataset:
P155 Incidence and significance of vitamin D deficiency at Inflammatory Bowel Disease inception in the COVID era
Authors: Rimmer P , Cheesbrough J , Palmer L , Meade I , Zaman Mim M T , Mohamed Z , Shariff S , Sharma N , Cooney R , Quraishi M N , Iqbal T
Published: January 2022

Background

Vitamin D, a key regulator of immune response, is known to be lower in Inflammatory Bowel Disease (IBD) patients than the general population. Disparity in the incidence of deficiency between ethnic groups has previously been demonstrated. We measured vitamin D in a unique multi-ethnic inception cohort to correlate this with traditional IBD scores and patient reported outcome measures including the ‘IBD Disk’.

Methods

Data regarding demographics, ethnicity, faecal calprotectin (FCAL) and baseline blood results including Vitamin D was collected prospectively from January-October 2021, from adults presenting with suspected IBD. Montreal classification, Harvey-Bradshaw Index or Partial Mayo score, endoscopic disease severity indices and IBD Disk score were documented in those with confirmed diagnosis at endoscopy. Vitamin D deficiency was defined as <50nmol/l.

Results

179 patients had a Vitamin D level recorded; 58 Ulcerative colitis (UC), 58 Crohn’s disease (CD), 53 non-IBD controls and 10 still awaiting diagnosis. 44(76%) CD, 32(55%) UC and 28(53%) non-IBD control patients were Vitamin D deficient at first presentation. Median levels were lowest in CD, with a significant difference between CD and non-IBD (median 35nmol/l; IQR 24.05 vs. median 48.9nmol/l; IQR 49.1; p=0.004). Regression analysis demonstrated patients with Crohn’s disease were four times more likely to have Vitamin D deficiency compared to UC (OR 4.08; 95% CI 1.35–12.36) at diagnosis. No correlation was seen between absolute vitamin D levels or vitamin deficiency state and faecal calprotectin when controlled for various factors regardless of the IBD subtype. The cohort distributions are demonstrated in Figure 1.

Within the IBD cohort, Vitamin D levels were significantly lower in Black or Asian patients vs White patients (median 28.5; IQR 20.85 vs median 43.3; IQR 33.95; p=0.004). Figure 2 provides an overview of the cohort distributions.

Vitamin D levels at presentation, as demonstrated in Table 1, did not correlate with Disease activity markers (DAMS) whereas baseline haemoglobin did, albeit weakly. Interestingly, Vitamin D and Haemoglobin correlated without reaching statistical significance (Spearman’s rho 0.149; p=0.08).

Conclusion

Our inception dataset demonstrates high rates of Vitamin D deficiency comparable to prior studies in IBD patients. Both CD and Black or Asian ethnicity were strongly associated with Vitamin D deficiency. Baseline Vitamin D did not correlate with disease activity markers whereas anaemia showed consistent weak association. Our study demonstrates the problem of hypovitaminosis D and the importance of measurement and supplementation, particularly in Black and Asian CD patients, from diagnosis.
P158 Disease and non-disease-related risk factors for inadequate bowel preparation in patients with inflammatory bowel disease: should the strategy be different?
Authors: Capela T , Macedo Silva V , Freitas M , Sousa Magalhães R , Cúrdia Gonçalves T , Dias de Castro F , Moreira M J , Cotter J
Published: January 2022

Background

Colonoscopy is of utmost importance in the management of inflammatory bowel disease (IBD) and is a critical tool for diagnostic and therapeutic decision-making. The quality of bowel preparation is important for the efficacy of colonoscopy and inadequate bowel preparation (IBP) is associated with increased costs and inconvenience. Most studies on IBP have not specifically evaluated the impact of concomitant conditions, such as IBD, on the quality of bowel preparation. We aimed to identify disease and non-disease related factors for IBP in patients with IBD submitted to colonoscopy.

Methods

Retrospective cohort-study which included adult IBD patients submitted to colonoscopy between 2016–2021. Patients’ demographic, comorbidities, clinical, biochemical, and colonoscopy data were recorded. IBP was defined as a final Boston Bowel Preparation Scale (BBPS) ≤5 or ≤1 in at least one segment. A univariable analysis tested the association between covariables and the outcome (IBP) in general and considering Crohn’s disease (CD) and ulcerative colitis (UC) patients separately. Statistically significant variables were included in multivariable logistic binary regression.

Results

Of 309 patients, 52.4% were female with a mean age of 43.7±13.7 years. Fifty one percent (n=158) had UC and 48.9% (n=151) had CD. Twenty-seven percent of the patients (n=82) had IBP which was not significantly different between UC and CD patients (40vs42, p=0.699, respectively). The presence of diabetes mellitus (adjusted OR 13.9 [95% CI 1.388–139.624], p<0.05) and antidepressant use (adjusted OR 4.1 [95% CI 1.247–13.625], p<0.05) were independently associated with the outcome in general. In contrast, only previous history of IBP (adjusted OR 3.1 [95% CI 1.184–8.271], p<0.05) was independently associated with the outcome in UC patients. Disease-related factors such as previous surgery, steroids, immunosuppressors or biologics and endoscopic activity were not associated with IBP.

Conclusion

This study demonstrates that the presence of diabetes mellitus and antidepressant use are predictors of inadequate bowel preparation for colonoscopy in patients with inflammatory bowel disease. Disease-related factors seem to have no influence in the quality of bowel preparation suggesting that a specific approach is unnecessary in these patients.
P163 Abdominal X-ray: an invaluable tool in Acute Severe Ulcerative Colitis
Authors: Correia J , Gomes C , Afecto E , Estevinho M , Rodrigues A , Silva A P , Fernandes C , Ponte A , Silva J C , Freitas T
Published: January 2022

Background

Intravenous steroids (IV-S) remain the cornerstone of treatment of Acute Severe Ulcerative Colitis (ASUC). However, one-third of these patients are refractory to this treatment. Several indices have been developed to predict the failure of IV-S for ASUC, using clinical data at day 3 of treatment. However, indices able to predict IV-S failure based on admission data are lacking.

Methods

A retrospective analysis of all consecutive hospital admissions due to ASUC, in a Portuguese tertiary centre, between February 2007 and April 2021 was performed. Only patients receiving IV-S for at least 3 consecutive days were included in this study. IV-S non-response was defined as the need for a second-line therapy or surgery. The following clinical data was collected from each patient: age, gender, disease duration, Montreal disease extension, previous ASUC, previous and on admission medical therapies (oral mesalazine, rectal mesalazine, oral steroids, immunosuppressants and monoclonal antibodies), fever on admission and weeks of symptoms’ worsening before admission. The following parameters on admission were also registered: C-reactive protein, albumin level, hemoglobin, leucocytes count, platelets count, Mayo endoscopic subscore and presence of transverse colonic dilatation on abdominal X-ray ≥5.5 cm. Univariate analysis was used to identify predictive factors of IV-S failure.

Results

68 patients (64.7% female), with a mean age of 40.4 (±16.2) years, were included in this study. 9 patients (13.2%) did not respond to IV-S therapy. On univariate analysis, only transverse colonic distension on X-ray was more frequent in IV-S non-responders (33.3% vs 6.8%, p=0.04).

Conclusion

Clinical data on admission, including previous medication, analytical parameters and endoscopic activity were not predictive of IV-S refractoriness in this population. However, abdominal X-ray showed to be useful to predict the need for a rescue therapy. These findings highlight, in one hand, the need of larger studies to identify on admission predictors of IV-S refractoriness and, in other hand, the importance of abdominal X-ray, in patients admitted due to ASUC.
P172 Examining dysplasia surveillance in Inflammatory Bowel Disease and Primary Sclerosing Cholangitis - a real world experience
Authors: Seah D , Gow P , Vaughan R , Grace J , De Cruz P , Choy M
Published: January 2022

Background

Patients with inflammatory bowel disease (IBD) and primary sclerosing cholangitis (PSC) are at high risk of developing colorectal cancer (CRC). Current guidelines recommend annual colonoscopic surveillance immediately following the diagnosis of PSC. This study aimed to assess the surveillance strategy and outcomes in IBD-PSC patients undergoing surveillance for colonic neoplasia (CN).

Methods

We performed a retrospective audit of all patients with IBD-PSC at an IBD and liver transplantation referral centre from 2013–2021, to determine the prevalence and management of dysplasia and CRC and evaluate the adequacy of colonoscopic surveillance. Surveillance was considered up-to-date if colonoscopy was performed at 12 month intervals +/- 3 months.

Results

Ninety-three patients diagnosed with IBD-PSC were identified. Patients who had undergone colectomy prior to enrolment or had colonoscopy performed externally were excluded. Sixty-nine patients were included in the final analysis. Thirty-three percent (23/69) of the cohort developed CN, with an overall rate of dysplasia of 25% (17/69) and CRC in 10% (7/69). Median time to development of CN from IBD diagnosis was 18 years (IQR 10.5–23.75). Only 23% (12/53) of patients were up-to-date with annual colonoscopic surveillance and following detection of neoplasia, chromoendoscopy was utilised in 9% of patients (2/23).

The rate of CN in patients with up-to-date surveillance was 6/12 (50%), three with low grade dysplasia (LGD) and three indefinite for dysplasia (IND), versus 10/41 (24%, p=0.89) in those without up-to-date surveillance, 6 with LGD, 1 with IND and 2 with CRC.

Rates of CN were not significantly different between patients who had or had not undergone liver transplantation (18/44 (41%) vs 6/25 (24%), p=0.16). Most patients were managed in Liver Transplant Unit (LTU) clinic (33/69, 48%). Forty-one percent (28/69) were seen in both LTU and IBD clinics, whilst a small number were seen in General Liver clinic (3/69, 4%) and IBD clinic (5/69, 7%) only. The rate of up-to-date surveillance was highest amongst those who were seen in both LTU and IBD clinics (8/28, 29%). In patients with CN, surgery was performed in 46% of cases (11/24): 25% (6/24) underwent sub-total colectomy; whereas, 21% (5/24) underwent segmental colectomy. Two patients developed recurrent dysplasia following segmental colectomy.

Conclusion

In this cohort of IBD-PSC, rates of dysplasia and CRC were high. Adherence to annual colonoscopy surveillance and chromoendoscopy was low. Surgical management of dysplasia or CRC varied. Multidisciplinary coordination between hepatology and IBD specialist services should be implemented to optimise dysplasia surveillance and management.
P199 Ileal pouch-anal anastomosis in women of childbearing age affected by ulcerative colitis: a single-centre study on the risk factors for infertility and outcomes of pregnancy over 17 years
Authors: Rottoli M , Pezzuto P , Fallani G , Pellino G , Rizzello F , Gionchetti P , Poggioli G
Published: January 2022

Background

The impact of Ileal Pouch-Anal Anastomosis (IPAA) on the fertility of women affected by ulcerative colitis (UC) is still debated in the literature. The primary aim of this study was to assess the risk factors for infertility in women undergoing IPAA. The second aim was compare the outcomes of pregnancy before and after IPAA.

Methods

Retrospective study including women (18–45 years) undergoing IPAA for UC (2004–2020). Univariate comparison was carried out as appropriate. Cox regression analysis was used to identify significant predictors of infertility over the follow-up (defined as the conceiving time starting one year after IPAA surgery).

Results

Some 149 patients answered the questionnaire and were included in the study. Table 1 shows the comparison between fertile (23, 15.5%) and infertile (20, 13.4%) women after IPAA surgery. At the cox regression analysis, only the Mayo endoscopic score of 3 was associated with the risk of postoperative infertility (OR 4.16, 95% CI 1.07–16.6, p=0.040).

Table 2 shows the comparison between pregnancies before (72) and after (27) IPAA. Pregnancies after IPAA were more likely to require assisted conception treatment (25.9% vs 2.7%, p<0.001), and to be carried out without any UC drug regimen (85.2% vs 61.1%, p=0.17), since they were less likely to trigger an exacerbation of the disease both during (8% vs 22.2%, p=0.09) and after pregnancy (24% vs 45.8%, p=0.044).

Of the 61 nulliparous women who did not try to conceive after IPAA, 11 (18%) feared physical consequences, 10 (16.4%) were afraid to transmit the disease, while 3 (4.9%) were recommended by their gynecologist.

Conclusion

IPAA surgery is associated with a reduction of the fertility of 46.5%, and the preoperative severity of the disease seems to be the strongest predictor of infertility. Although the pregnancy after IPAA requires a longer conceiving time, it is safe for both the mother and the child, at least when carried out through caesarean delivery. A great proportion of women of childbearing age affected by UC still refer confusion regarding the risks of complications and infertility associated with IPAA. A dedicated counsel pathway should be mandatory in all referral centres. A larger multicentric study will be required to assess the outcomes in a larger population.
P213 Risk factors associated with NAFLD and liver fibrosis in patients with Inflammatory Bowel Disease: a prospective cohort study
Authors: Martínez-Domínguez S J , García Mateo S , Gallego Llera B , Gargallo-Puyuelo C J , Refaie E , Arroyo Villarino M T , Laredo de la Torre V , Alfambra Cabrejas E , Gomollón García F
Published: January 2022

Background

Non Alcoholic Fatty Liver Disease (NAFLD) prevalence is increasing quickly all over the world. A higher prevalence has been reported in Inflammatory Bowel Disease (IBD) patients. NAFLD is associated with increased mortality from liver and cardiovascular causes, so defining risk factors is clinically very relevant.

Methods

Consecutive IBD patients ≥ 18 years were evaluated at a reference center from October 2020 to April 2021, after giving their informed consent. They were investigated the presence of NAFLD by hepatic ultrasonography and Controlled Attenuation Parameter (CAP) performed by two trained gastroenterologists, considering steatosis in case of any degree of ultrasound steatosis or CAP > 245 dB/m. Risk of advanced liver fibrosis was considered if transient elastography was ≥ 8 kPa. Patients with risk alcohol consumption, secondary causes of steatosis or any chronic hepatic disease were excluded. In addition, a blood sample was obtained for biochemical parameters, clinical variables were recovered prospectively and medical records were reviewed. A descriptive analysis was carried out and factors potentially associated with NAFLD and liver fibrosis were analysed through logistic regression multivariate analyses. For all tests a two-sided p value <0.05 was considered statistically significant. The study was approved by local Ethical Committee.

Results

700 patients (50% women) with a median age of 50 (IQR (40–60)) years were included. In 377 (53.9%) the diagnosis was Ulcerative Colitis and in 323 (46.1%) Crohn′s Disease, the median age at diagnosis was 33 (IQR (22–42)) years. 131 (18.7%) had obesity and 238 (34%) had overweight. The prevalence of NAFLD was 42.57% and the prevalence of liver fibrosis was 7.31%.

In multivariate analysis, NAFLD was significantly associated with older age (OR (CI 95%) 1.04 (1.02–1.06), p <0.001), obesity/overweight (OR (CI 95%) 0.26 (0.17–0.39), p <0.001), waist-to-hit ratio (OR (CI 95%) 0.32 (0.21–0.48), p <0.001) and absence of active lifestyle (OR (CI 95%) 2.41 (1.44–4.05), p<0.001). No significant association was found between NAFLD and type of IBD, location, extension, pattern or the treatment of the disease. Hepatic fibrosis was significantly associated with hypertension (OR (CI 95%) 0.07 (0.10–0.45), p= 0.006) and surgical reintervention for IBD (OR (CI 95%) 6.41 (1.06–38.83), p= 0.043) in multivariate analysis, without significant association with other comorbidities, type and location of IBD or pharmacological treatment.

Conclusion

NAFLD is very prevalent in IBD and seems to be associated with the same risk factors than in the general population. Screening for NAFLD seems warranted in all IBD patients.
P224 Deconstructing distress: Stakeholder engagement for evidence-based, patient-centered interventions for the management of IBD-associated psychological distress
Authors: Heisler C G , Rohatinsky N , Stewart M , Vallis M , Shepherd T , Wozney L , Cassidy C , Currie B , Phalen-Kelly K , Robar J , Targownik L , Huard T , Neil E , Jones J
Published: January 2022

Background

The growing prevalence of Inflammatory Bowel Disease (IBD) along with increasing complexity of providing high-quality, patient-centered care within a resource-constrained healthcare environment presents a major challenge. IBD-related psychological distress (IBD-PD) is the emotional impact of IBD and is associated with mental health disorders, increased disease severity, and premature mortality. With estimates of nearly 90% of IBD patients experiencing PD, the inability to provide high-quality, person- centered care for IBD- PD that is proportionate to clinical need is a significant care gap in the Canadian healthcare system. The aim of this project was to generate stakeholder-derived data to inform the design and development of stepped-intensity, cognitive behavioral therapy-based interventions for IBD-PD using evidence-based, patient–centered interventions and implementation strategies.

Methods

Virtual semi-structured interviews were conducted from September to October 2021. The interview guide was developed iteratively by researchers, IBD care providers, and patient research partners and guided by the COM-B Model of Behaviour and the Theoretical Domains Framework. Interview questions assessed perceptions, experiences, barriers, and facilitators to accessing IBD-PD care. Adults diagnosed with IBD were recruited from academic centers across Canada. Interviews were co-facilitated by a researcher and patient research partner, audio recorded, and transcribed. Using thematic analysis, codes were generated to identify themes using an inductive approach.

Results

As of October 2021, eleven interviews have been completed, with data collection ongoing. The mean participant age was 33.5 years (range 21–55 years) with 63.6% of respondents identified as female (7/11). The majority of participants worked full time (8/11, 72.7%) and all had completed at least high school. Diagnoses of Crohn’s Disease (7/11, 63.6%) were more common than ulcerative colitis (4/11, 36.4%) among the participants. Thematic analyses identified five major themes: 1) Lack of holistic care and acknowledgement of IBD-PD; 2) System-level and financial barriers to psychological support; 3) Lack of psychological support from providers with an understanding of IBD; 4) Preference for individualized virtual-based support; 5) Heavy reliance on informal support structures (caregivers) due to lack of access to formal psychological support.

Conclusion

As part of human-centered design, stakeholder engagement is key to understanding behavioral, social, attitudinal, and environmental barriers and facilitators for accessing IBD-PD care. Interviews are ongoing and specific intervention functions will be defined and incorporated into patient-centered implementation strategies.
P254 Crohn’s disease of the pouch: an overdiagnosed condition?
Authors: de Jong D C , Reijntjes M , Wessels E , Buskens C , Hompes R , Löwenberg M , Gecse K , D’Haens G , Bemelman W , Duijvestein M
Published: January 2022

Background

Approximately 10% of ulcerative colitis (UC) patients undergoing ileal pouch-anal anastomosis (IPAA) are believed to develop ‘de novo Crohn’s disease’ (CD) of the pouch (1). Clear diagnostic criteria are lacking, but the diagnosis is mostly based on the development of fistula, strictures, treatment refractory disease, pre-pouch ileitis, or typical endoscopic findings fitting with CD, such as ulcers and patchy inflammation (1, 2). However, the findings on which this diagnosis is established may be caused by (unrecognized) surgical complications such as silent anastomotic leakage. It is important to distinguish these complications from what is truly a ‘de novo CD’ as treatment strategies differ in both groups. We aimed to investigate incidence rates and reasons for diagnosing CD of the pouch.

Methods

In total, 483 consecutive UC patients who underwent a proctocolectomy and IPAA in a tertiary IBD referral centre from January 1990 until December 2017 were retrospectively reviewed. Patients with a diagnosis ‘CD of the pouch’ were identified based on medical records, and could be based on either clinical, endoscopic, imaging and/or histological findings.

Results

Median follow-up time was 20 years (IQR 10 – 24). In 46 out of 483 patients (10%), de novo CD of the pouch was diagnosed, which was mostly based on endoscopic findings (29/46, 63%). Presence of pre-pouch ileitis was the most common reason to diagnose CD of the pouch, which was present in 18/29 patients (62%), followed by ulcerations in 6/29 (21%). On MRE, 19/46 (41%) patients had a fistula or sinus, 4/46 patients (9%) had a stricture (all proximal of the pouch). Interestingly, 12/46 patients (26%) never underwent cross sectional imaging after IPAA construction.

Only ten patients (22%) showed histologic findings with a preference for CD in biopsies, revised colectomy specimen, and/or pouch excision specimen. Only two patients had granulomas, others showed signs of transmural inflammation, ulcerations or fibrosis. Other histologic findings were non-specific.

Conclusion

In our centre, 10% of patients were ‘diagnosed’ with de novo CD of the pouch. However, as confirmatory histological signs of CD were present in only 22%, chronic surgical complications as underlying cause might be of greater importance. It is advised to perform cross sectional imaging in every patient after a year after pouch construction to rule out silent leaks that might cause symptoms at a later stage mimicking Crohn’s disease, avoiding a diagnostic dilemma.
P280 Prognosis of patients with Crohns Disease in transmural remission with gastrointestinal ultrasound
Authors: Nylund K , Sævik F , von Volkmann H L , Gilja O H
Published: January 2022

Background

Gastrointestinal ultrasound (GIUS) can be used to measure bowel wall thickness (BWT). If the bowel wall is less than 3 mm in all bowel segments in a patient with Crohn’s disease(CD) this predicts endoscopic remission with a high degree of accuracy, but still some CD patients with disease located to the terminal ileum and colon will have a thickened bowel wall even if they are in endoscopic remission. Could BWT be an independent predictor of disease activity in CD? The aim of the study was to investigate if a normalisation of bowel wall thickness in CD patients affects risk for important negative clinical endpoints such as need for corticosteroids, failure in maintenance treatment, hospital admissions and surgery.

Methods

Patients with CD referred to the Haukeland University Hospital for ileocolonoscopy were examined with GIUS and followed for at least 12 months. The clinical endpoints examined were defined as the need for short- or long-time treatment with corticosteroids, changes in the maintenance treatment including drug switch and dose adjustments, hospital admissions and any surgical procedure that could be related to Crohn’s disease. Patients were categorized into 3 groups according to their findings on endoscopy and GIUS: The activity group (1) consisted of patients with activity on GIUS defined as any bowel wall segment ≥3mm and Simple Endoscopic score of Crohn’s disease (SES-CD) >2. The group in transmural remission (2) was defined as all patients with BWT <3mm independent of findings on endoscopy. The final group (3) consisted of the patients with isolated endoscopic remission defined as SES-CD ≤2 and BWT ≥3mm in one or more bowel segment.

Results

155 CD patients were included in the study. In total 61/155 patients experienced one or more negative, clinical endpoint during the one year follow up period. 9/155 received treatment with corticosteroids, 50/155 had adjustments in their medical therapy, 32/155 were admitted to the hospital at least once and 18/155 had surgery. In group 1, 44/92 experienced one or more endpoints while the corresponding numbers were 9/40 in group 2 and 8/23 in group 3. The frequency of clinical endpoints were significantly different between the different groups (p=0,020, Fischer’s exact test). Only patients in group 1 were operated.

Conclusion

The group with transmural remission had fewer patients with negative, clinical endpoints which suggests that GIUS is well suited for distinguishing between CD patients with high or low risk for negative clinical endpoints.
P282 Influence of phenotype at diagnosis and of other potential prognostic factors on the prognosis of Crohn’s Disease in Chinese population
Authors: Xiao Z , Wu L , Cao Q
Published: January 2022

Background

L4 Crohn’s disease (CD) is defined as any lesion location proximal to terminal ileum according to Montreal classification. L4 disease was considered to associated with poor prognosis. However, the outcome of CD patients with esophagogastroduodenal disease and small intestinal lesions remains to clarified. Our aim was to confirm whether the outcome diffs among the patients with different L4 disease.

Methods

Our study included 670 patients who confirmed CD between January 2014 and December 2020 retrospectively. As similar as Paris classification, we divide L4-disease in adult into L4a and L4b with a ligament of Treitz as a boundary. The primary outcome was defined as intestinal surgery. Clinical manifestation and outcomes were compared among L4a, L4b, and non-L4 disease.

Results

Totally 237(10.0%) patients had isolated L4 disease or L4 disease concomitant non-L4 disease. Among them, 67(10.0%) patients suffered from L4a disease and 168(25.1%) patients has a L4b disease. Patients with L4b disease were more likely to undergo intestinal surgery compared to L4a and non-L4 disease (41.7% versus 9.0% and 21.8%, respectively, both p<0.0001). However, L4a wasn’t a risk factor for intestinal surgery than non-L4 disease(9% versus 21.8%, p=0.074). At diagnosis, L4b group has a higher percentage of intestinal obstruction than L4-GD and non-L4 group (39.3% versus 17.9% and 22.4%, respectively, p=0.0021 and p<0.0001). Results of multivariate analysis also showed that intestinal obstruction at diagnosis, disease behavior and disease location was a independent predictors for intestinal resection, and L4b (HR 1.786; 95%CI 1.302–2.303, p=0.0032) show significant differences between non-L4 disease.

Conclusion

Within L4 disease, L4b disease was a risk factor associated a poor prognosis compared to non-L4 disease. But the same result can’t be found in L4a disease. It might indicate that we need divide L4 phenotype of Montreal classification into L4a subgroup and L4b subgroup, and treat patients with L4-intestnal disease with biological agents earlier.
P294 On the way to disease control: Fatigue as part of a novel composite endpoint in an analysis of a prospective open label observation trial
Authors: Tran F , Nikolaus S , Schrinner F , Kümpers J , Lessing A , Lintner J , Lessing M , Sievers L K , Rosenstiel P , Aden K , Franke A , Schreiber S
Published: January 2022

Background

Ambitious therapeutic goals in the therapy of inflammatory bowel disease need more stringent individual endpoints. Several definitions for composite endpoints are under evaluation to describe disease control. Most commonly symptomatic (PRO2) remission is combined with endoscopic response, histology and/or biomarker remission. Here we explore the addition of fatigues as a lead problem reported by patients with IBD as part of a composite endpoint.

Methods

We have conducted an interim analysis of an ongoing open label study of patients with Crohn’s disease (CD) and ulcerative colitis (UC) assigned to anti-TNF therapy, vedolizumab, ustekinumab or tofacitinib. Patients are scheduled for evaluations at start of the respective therapy and at weeks 2, 6, 14, 26 and 52. Endoscopies are conducted before therapy and at weeks 14 and 52. Clinical remission (CR) was defined as CDAI < 150 and reduction of partial Mayo score (pMayo) > 50% vs. baseline at week 14. All patients who are not in CR and/or no improvement in endoscopy at week 14 are assessed for a switch in the mechanism of action and observation schedules after a switch are reset to week 0. FACIT-F scores <30 was defined as clinically relevant fatigue.

Results

Fatigue was present in 52% patients (39/75) at baseline. 54% (25/46) of the patients achieved CR at week 14 while 46% (21/46) did not meet CR criteria (non-responder). Fatigue at baseline was persistent at week 14 in 12% (3/25) of CR responders, in contrast to 43 % (9/21) of non-responders. 64% (21/33) of all patients reached a combined endpoint of CR and absence of fatigue. If fatigue was present at baseline (n = 25), fatigue response was observed in 52% (13/25) of the patients, while CR was only reached in 40% (10/25) and the combined endpoint of CR and fatigue response in 24% (6/25) of the patients at week 14. In contrast, 71% (15/21) of patients without fatigue at baseline reached CR at week 14. Absence of fatigue at baseline thus increased the chance of CR at week 14, with an OR of 3.75 [1.031 – 11.50] (p = 0.0422 in Fisher’s exact test).

Conclusion

Fatigue is an important complaint strongly impacting the patients’ quality of life. A composite endpoint including fatigue and clinical remission (based on pMayo and CDAI) can be reached in a significant percentage of patients treated with biological therapies. Presence of fatigue at baseline might serve as a strong marker for clinical non-response at week 14. Further evaluation and replication of this novel composite endpoint will be conducted in our ongoing trial with a particular focus on inclusion of endoscopies and long-term outcome.
P297 Treatment of patients with complex perianal Crohn’s disease with darvadstrocel: a single-institution real life experience
Authors: Borruel PhD N , Martí M , Armario D , Ibarz A , Robles V , Herrera C , Mayorga L , Pérez Z , Alonso C , Elena C , Planes M , Oller E , Espín E , Casellas F
Published: January 2022

Background

Complex perianal disease in patients with Crohn’s disease (CD) represents a therapeutic challenge since, despite biological treatment, half of the patients do not achieve an adequate response. Treatment with allogenic expanded adipose-derived mesenchymal stem cells (Darvadstrocel) has proven to be an innovative treatment in patients refractory to treatment with immunomodulators and anti-TNF antibodies.

Methods

To assess the efficacy of Darvadstrocel treatment in clinical practice in patients with CD and complex perianal fistula. Method: We performed a prospective descriptive study in patients with CD and complex perianal fistula (high intersphincteric, transsphincteric, extrasphincteric or suprasphincteric; presence or ≥ 2 external opening or abscesses), refractory to antiTNF treatment, treated consecutively with Darvadstrocel at our Crohn’s and Colitis Attention Unit. Each patient was treated with 120 million stem cells (half of the dose was injected along the tract walls and the other

half around the internal opening/s). Response to treatment was assessed as combined remission according to the criteria of the ADMIRE study (clinical assessment of closure of all treated external openings that drained before treatment and absence of collections> 2 cm confirmed by MRI).

Results

From July 2020 to October 2021 12 patients (10M / 2H) have been treated with Darvadstrocel. All patients were in clinical remission (luminal disease) and had perianal disease refractory to anti-TNF treatment. In addition, 7/12 patients were also refractory to ustekinumab. The patients had previously been treated with a mean of 5.7 perianal surgeries (1–16), most of them curettage and seton placement or replacement. One patient had previously been treated with mesenchymal stem cells in 2014 (ADMIRE participant). All fistulas were complex, 5 with a single tract, 2 with a branched tract and 5 with a double tract; 7 were transsphincteric, 1 intersphincteric (double), 1 supraelevator, 1 suprasphincteric, and 2 extrasphincteric. 6/10 patients underwent a previous conditioning surgery (cleaning, curettage and seton placement) two weeks before cell administration. Six of the 10 patients with a follow-up of at least 6 months had combined remission (60%). Two of the three patients with a 1-year follow-up presented combined remission. Regarding safety, no relevant adverse effects have been observed: 2 patients presented abscesses in the immediate postoperative period (self-drained without subsequent recurrence).

Conclusion

In real-life clinical practice, treatment with Darvadstrocel can be an effective and safe therapy in patients with CD and complex perianal disease refractory to biological treatment.
P305 Low ALT is more Common in Patients with IBD than Healthy Controls and is Associated with Active Disease
Authors: Shafrir A , Katz L , Zinger A , Safadi R , Kaliski I
Published: January 2022

Background

Sarcopenia is underdiagnosed in patients with Inflammatory bowel disease (IBD). Studies have shown that low alanine transaminase (ALT) levels are associated with sarcopenia. We evaluated the association of low ALT levels with the IBD diagnosis and activity.

Methods

Data of patients from state mandatory health maintenance organization in Israel was collected. Electronic medical records within the past two years included diagnosis, medications, blood and stool tests. Based on ICD9 coding, patients diagnosed with Ulcerative Colitis (UC) or Crohn’s disease (CD) were compared to healthy control group. Patients with ICD9 diagnosis of chronic liver disease, cirrhosis, and age <18 were not included. Serum ALT lower than, 15 was considered low.

Results

Our cohort consisted of, 348,454 patients, of them, 1780 patients with CD and, 916 with UC. Mean ALT was lower among patients with IBD than healthy controls (22.71 vs., 24.04, p-value<0.001). In multivariate logistic regression, controlling for age, sex, BMI, and smoking status, IBD was associated with low ALT levels (OR –, 1.25, 95% CI, 1.12–1.39, p-value<0.001)

Of the CD patients, 392 (27.96%) were in the low ALT group. Patients in the low ALT group were younger (38.85 vs., 42.38 p- value<0.001), were less likely to be male (33.9% vs., 54.7%), had lower BMI (23.94 vs., 26.29 p – value<0.001). Fecal Calprotectin and CRP was higher in the low ALT group (601.25 vs., 282.33 p-value<0.001, 12.94 vs., 7.35 p value<0.001 respectively) while serum albumin was lower (4.12 vs., 4.28 p-value<0.001).

Among patients with UC, 204 (30.13%), had low ALT. Patients in the low ALT group were slightly younger (46.92 vs., 49.65 p-value=0.06), less likely to be male, 22.5% vs., 52% p-value<0.001), had lower BMI (25 vs., 26.37 p-value=0.004). Patients with low ALT had higher CRP levels (12.92 vs., 6 p-value<0.001) and non-significantly higher fecal calprotectin levels (779.52 vs., 498.18 p-value, 0.16). Serum albumin was lower in the low ALT group (4.04 vs., 4.26 p value<0.001)

In multivariate linear regression models, controlling for age, gender IBD subtype, and smoking status, low ALT was associated with elevated fecal calprotectin and CRP and lower albumin levels (p-value<0.001).

Conclusion

Patients with IBD have lower ALT levels than the general population. Among patients with IBD, low ALT is associated with active disease. Further studies are warranted to strengthen the association of low ALT with sarcopenia among patients with IBD.
P361 PREPARE-IBD: Physician Responses to disease Flares and Patient Adaptation in Relation to Events in Inflammatory Bowel Disease during the COVID-19 pandemic: A multicentre cohort analysis
Authors: Saifuddin A , Kent A , Mehta S , Hicks L , Gonzalez H , Segal J , Brooks M , Subramanian S , Bhala N , Conley T , Patel K , Lamb C , Walker G , Kennedy N , Sebastian S
Published: January 2022

Background

The COVID-19 pandemic continues to pose complex problems across Europe and the world, with rising numbers of infections and the ongoing need for drastic public health interventions. This is difficult for patients with immune-mediated disorders like Inflammatory Bowel Disease (IBD), where immunosuppressive medications may affect susceptibility to serious infection. It was particularly challenging for physicians and patients during the first wave of the pandemic, when it was unclear whether anti-inflammatory flare treatment should be adapted to reduce infection risk, whilst trying to ensure symptomatic control and avoid admission to overwhelmed hospitals. Despite the development of various IBD / COVID-19 databases, the treatment adaptations and outcomes of patients experiencing IBD flares during the COVID-19 pandemic remain undefined. We aimed to compare IBD management and outcomes between pandemic and pre-pandemic cohorts.

Methods

An observational cohort study was performed, comprising patients who contacted IBD teams for a symptom flare between March – June, 2020 in, 60 National Health Service trusts in the United Kingdom. Data were compared to a pre-pandemic cohort after propensity-matching for age and disease severity. Statistical analyses were performed using R (version, 4.1.0, Vienna, Austria).

Results

In total, 3728 patients in the pandemic (n=1864) and pre-pandemic (n=1864) cohorts were included. The principal findings were reduced systemic corticosteroid prescription during the pandemic in both Crohn’s disease (prednisolone: pandemic, 199/752, 26.5% vs, 263/708, 37.1%; p<0.001) and ulcerative colitis (UC) (prednisolone: pandemic, 372/1112, 33.5% vs, 470/1156, 40.7%, p<0.001), with increases in poorly bioavailable oral corticosteroids in Crohn’s (pandemic, 117/752, 15.6% vs, 48/708, 6.8%; p<0.001) and UC (pandemic, 131/1112, 11.8% vs, 60/1156, 5.2%; p<0.001). Ustekinumab (Crohn’s and UC) and vedolizumab (UC) treatment also significantly increased during the pandemic. Three-month steroid-free remission was similar in both Crohn’s (pandemic, 175/616, 28.4% vs, 195/608, 32.1%; p=0.17) and UC (pandemic, 312/858, 36.4% vs, 404/1006, 40.2%; p=0.095). The, 65 patients experiencing a flare and COVID-19 were more likely to have moderate-to-severely active disease at three months compared to those with a flare alone.

Conclusion

Despite several treatment adaptations during the pandemic, steroid-free outcomes were comparable to pre-pandemic levels, though patients with a flare and COVID-19 experienced worse outcomes. These findings have implications for IBD management during future waves or pandemics
P385 Tailoring induction treatment for children with Crohn’s disease
Authors: Cuomo M , Carobbio A , Aloi M , Alvisi P , Banzato C , Bosa L , Bramuzzo M , Campanozzi A , Catassi G , D’Antiga L , Di Paola M , Felici E , Fioretti M T , Gatti S , Graziano F , Lega S , Lionetti P , Marseglia A , Martinelli M , Musto F , Sansotta N , Scarallo L , Zuin G , Norsa L
Published: January 2022

Background

Multiple clinical studies in children with Crohn’s disease (CD) have demonstrated the high efficacy of nutritional therapy with exclusive enteral nutrition (EEN) to induce remission and even to promote mucosal healing.

However, EEN as inductive treatment may be not tolerated or inefficient and we are well aware of the paramount importance of a well conducted induction treatment for paediatric CD with the goal of an individualized induction treatment to improve the prognosis and the quality of life of inflammatory bowel disease (IBD) children.

Methods

A retrospective multicentre study including newly diagnosed children with CD treated with EEN as induction therapy was designed. The primary aim of the study was to study predictive factors of non- adherence to treatment. The secondary endpoint were predictive factors of clinical non-remission at the end of induction treatment. Those data together were analysed with the ultimate goal of trying to define an individualized induction treatment for children with CD.

Results

376 CD children from, 14 IBD paediatric referral centres were enrolled in the study. The rate of EEN adherence was, 89 %. Colonic involvement and FC >, 600 μg/g at diagnosis were found associated with a reduced EEN adherence in univariate and multivariate analysis. The remission rate of those who completed induction treatment was, 67%. A multivariate analysis showed that factor determining lower remission rate were age >, 15 years and PCDAI >, 50. With those results we were able to create a decisional algorithm which is provided in figure 1.

Conclusion

EEN administered for, 8 weeks is effective for inducing clinical remission. The rate of adherence is high but there is a group of patients (colonic involvement + hight FC) which are at risk of non-adherence and thus may be candidate for alternative dietary induction regimens. Moreover, older patients with moderate to severe active disease (PCDAI>40), are at higher risk of failing clinical remission achievement after EEN and may benefit from an early anti-TNF alpha treatment. Personalized treatment strategies should be proposed weighing the benefits and risks based on each patient’s disease location, phenotype and disease activity with the overall aim of obtaining rapid control of inflammation to reduce long-term bowel damage.
P389 Indicators for inadequate response to advanced therapy in patients with Ulcerative Colitis: results from a medical chart review in the United Kingdom
Authors: Lindsay J , Picker N , Kromer D , Smyth M , Patel H
Published: January 2022

Background

Patients with Ulcerative Colitis (UC) who commence advanced therapy may experience inadequate response or require therapy modification to achieve remission. Therapeutic modification increases health care costs and is associated with adverse events. This study aimed to examine the rates of inadequate response, therapeutic modification and subsequent remission among UC patients starting advanced therapy in the UK.

Methods

Using a retrospective chart review, patients with UC treated with an advanced therapy (adalimumab, infliximab, golimumab, vedolizumab, and tofacitinib) between, 01/2017 and, 09/2019 were selected from, 8 clinics across the UK. Patients with ≥12 months of data before and after starting an advanced therapy (Index Date) were included. Inadequate response was defined as at least one of the following events: index therapy discontinuation or switch due to lack of response, therapy escalation, augmentation with an additional conventional therapy, corticosteroid (CS) dependency (use for ≥12 weeks), new CS initiation, UC-related hospitalisation, surgery, or emergency department visit. Remission was assessed using components of the Mayo score. Kaplan-Meier analysis was used to examine remission rates over, 24 months. Subgroups included patients with prior exposure to biologics, and patients with vs. without remission at, 12 months. Factors associated with time to remission were assessed in a multivariate Cox regression model.

Results

Among, 238 patients included (female:, 46.6%; median age, 42 years; median follow-up:, 28.8 months), 178 (74.8%) patients were biologic-naïve, and, 60 (25.2%) were biologic-experienced. At, 12 months, 105 (44.3%) patients had ≥1 indicator for an inadequate response (Figure, 1); the median time to first event was, 18 months. Among those who discontinued (N=72), 69.4% switched to another advanced therapy. Inadequate response was more frequent in biologic-naïve vs. experienced patients (50.3% vs., 26.7%; p<0.01) and among those without vs. with remission (56.3% vs., 34.4%; p<0.01). At, 12 months, 61 patients (46.1%) had not achieved remission (median time to remission:, 7.6 months; Figure, 2). At, 12 months, one third (33.0%) of patients in remission required therapy modification (augmentation, dose escalation, and use of CS). In an adjusted model, chances of remission were halved in biologic-experienced patients vs. naive patients (hazard ratio:, 0.49; p<0.05).

Conclusion

More than two-fifths of UC patients had an inadequate response, and nearly half did not achieve remission within one year after therapy start. Even among patients in remission, one third required additional therapy modifications. More effective therapies are needed to achieve better outcomes for patients with UC.
P407 A Phase IB/IIA study of remestemcel-L, an allogeneic bone marrow derived mesenchymal stem cell product, for the treatment of medically refractory ulcerative colitis: An interim analysis
Authors: Lightner A , Dadgar N , Fulmer C , Ream J , Nachand D , Steele S
Published: January 2022

Background

Direct injection of mesenchymal stem cells (MSCs) have been used for the treatment of perianal Crohn’s fistulizing disease. However, no studies have looked at the direct injection of MSCs for luminal ulcerative colitis (UC).

Methods

Following screening and informed consent, patients with medically refractory UC were randomized in a, 2:1 fashion to receive remestemcel-L, an ex vivo expanded allogeneic bone marrow derived MSC product, at a dose of, 150 or, 300 million MSCs versus placebo delivered via direct injection using a, 23 G sclerotherapy needle at the time of colonoscopy. Patients were included if they had medically refractory UC defined as an established diagnosis for at least, 6 months prior to study enrollment and had lost response to at least one monoclonal antibody in the past. Patients were evaluated with validated clinical and endoscopic scoring systems at, 2 weeks, 6 weeks, and, 3 months post MSC delivery. Patients randomized to control crossed over at, 3 months to receive MSC treatment and followed the same schedule for post MSC evaluation.

Results

A total of six patients were enrolled and treated;, 4 were randomized to treatment and, 2 to placebo. All had been on prior anti-TNF or anti integrin-therapy. There were no adverse and serious adverse events related to investigational product.

In the treatment group (n=4), the Mayo score and Mayo endoscopic severity score decreased in all patients by two weeks after MSC delivery. By six weeks post MSC treatment, all treated patients had achieved clinical and endoscopic remission as defined by the Mayo score and Mayo endoscopic severity score. Patient reported number of daily bowel movements decreased as did urgency and presence of blood in the stool. With regard to patient reported outcomes, at three months, based on the inflammatory bowel disease patient reported treatment impact (IBD-PRTI), all patients were extremely satisfied or satisfied with their MSC treatment. Treated response was described as excellent or good in all patients.

In the control group (n=2), the Mayo score did not decrease. Patient reported number of daily bowel movements increased as did the number reporting blood in their stool; urgency remained unchanged. With regard to patient reported outcomes, at three months, based on the IBD-PRTI, one patient was neutral, and one patient was dissatisfied. Treated response was described as poor or unchanged in control patients.

Conclusion

MSCs offer a safe alternative therapeutic for the treatment of medically refractory UC. Early data suggests improved clinical and endoscopic scores by as early as two weeks following MSC delivery.