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Background: Fatigue is commonly reported by patients with inflammatory bowel disease [IBD], but the determinants of IBD-related fatigue have yet to be determined., Aims: To identify the factors associated with fatigue in a large population of patients with IBD., Patients and Methods: Fatigue and nine other IBD-related disability dimensions were assessed in a cohort of 1704 consecutive patients with IBD using the IBD-disk questionnaire in a cross-sectional survey of 42 French and Belgian centres. Fatigue and severe fatigue were defined as energy subscores >5 and >7, respectively. Determinants of fatigue were assessed using univariate and multivariate analyses (odds ratios [ORs] are provided with 95% confidence intervals)., Results: The prevalence rates of fatigue and severe fatigue were 54.1% and 37.1%, respectively. Both fatigue and severe fatigue were significantly higher in patients with active disease than in patients with inactive disease [64.9% vs 44.7% and 47.4% vs 28.6%, respectively; p < 0.001 for both comparisons]. In the multivariate analysis stratified by age, sex, type of IBD and IBD activity, fatigue was associated with age >40 years (OR = 0.71 [0.54-0.93]), female sex (OR = 1.48 [1.13-1.93]) and IBD-related sick leave (OR = 1.61 [1.19-2.16]), and joint pain (OR = 1.60 [1.17-2.18]), abdominal pain (OR = 1.78 [1.29-2.45]), regulating defecation (OR = 1.67 [1.20-2.32]), education and work (OR = 1.96 [1.40-2.75]), body image (OR = 1.38 [1.02-1.86]), sleep (OR = 3.60 [2.66-4.88]) and emotions (OR = 3.60 [2.66-4.88]) subscores >5., Conclusion: Determinants of fatigue are not restricted to IBD-related factors but also include social factors, sleep and emotional disturbances, thus supporting a holistic approach to IBD patient care., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background and Aims: Optimal management of patients with inflammatory bowel disease [IBD] after anti-tumour necrosis factor [TNF] discontinuation due to severe induced skin lesions is unclear. Our study aimed to describe dermatological and IBD evolution after anti-TNF discontinuation for this side effect., Methods: We conducted a multicentre retrospective study including consecutive IBD patients who discontinued anti-TNF due to severe induced skin lesions. Our objectives were to determine factors associated with dermatological remission [complete disappearance of skin lesions] and with IBD relapse in patients with inactive disease at inclusion, notably the impact of an early switch to another biological agent within 3 months of anti-TNF discontinuation., Results: Among the 181 patients [134 women, 160 Crohn's disease] included in the 13 participating centres, dermatological remission occurred in 110 [62%] patients with a median [interquartile range, IQR] interval of 8.0 [6.8-11.0] months. Scalp location was independently associated with less remission of skin lesions (hazard ratio [HR] = 0.64 [95% CI 0.43-0.94], p = 0.02) while early switch was independently associated with a higher probability of remission of skin lesions (HR = 1.64 [95% CI 1.1-2.5], p = 0.02). Among the 148 patients with inactive IBD at inclusion, disease relapse occurred in 75 [51%] patients with a median [IQR] interval of 26.0 [23.0-39.1] months. Survival rates without IBD relapse at 1 year were 85.8% [95% CI 77.5-94.9] in the early switch group and 59.3% [95% CI 48.9-71.9] in the other group [p < 0.01]., Conclusions: Early switch to a new biological is associated with a higher probability of healing of anti-TNF-induced skin lesions and significantly reduces the risk of IBD relapse., (© The Author(s) 2022. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background and Aims: Risankizumab, an interleukin-23 antibody, demonstrated efficacy and acceptable safety in a phase 2 study of patients with moderate-to-severe refractory Crohn's disease. This open-label extension investigated the long-term safety, pharmacokinetics, immunogenicity and efficacy of risankizumab in responders to risankizumab in the parent phase 2 study., Methods: Enrolled patients had achieved clinical response [decrease in Crohn's Disease Activity Index from baseline ≥100] without clinical remission [Crohn's Disease Activity Index <150] at Week 26, or clinical response and/or remission at Week 52 in the parent phase 2 study and received open-label subcutaneous risankizumab 180 mg every 8 weeks., Results: Sixty-five patients were enrolled, including four who had lost response in the parent study and were first reinduced with risankizumab 600 mg every 4 weeks [three infusions]. Patients received risankizumab for a median of 33 months [total: 167.0 patient-years]. The rate of serious adverse events was 24.6 events/100 patient-years; the majority were gastrointestinal in nature. Rates of serious infections, opportunistic infections and fungal infections were 4.2, 1.8, and 6.6 events/100 patient-years, respectively. No deaths, malignancies, adjudicated major adverse cardiovascular events, latent/active tuberculosis or herpes zoster were reported. Treatment-emergent anti-drug antibodies developed in eight patients [12.3%]; none were neutralizing. Efficacy outcomes were maintained during the study, including the proportions of patients [observed analysis] with clinical remission [>71%] and endoscopic remission [>42%]., Conclusions: Long-term maintenance treatment with subcutaneous risankizumab 180 mg every 8 weeks was well tolerated by patients with Crohn's disease, with no new safety signals. Clinical trial registration number: NCT02513459., (© The Author(s) 2021. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation.)

Background and Aim: The inflammatory bowel disease [IBD]-disk is a 10-item self-questionnaire that is used to assess IBD-related disability. The aim of the present study was to evaluate this tool in the assessment of IBD daily-life burden., Methods: A 1-week cross-sectional study was conducted in 42 centres affiliated in France and Belgium. Patients were asked to complete the IBD-disk [best score: 0, worst score: 100] and a visual analogue scale [VAS] of IBD daily-life burden [best score: 0, worst score: 10]. Analyses included internal consistency, correlation analysis, and diagnostic performance assessment., Results: Among the 2011 IBD outpatients who responded to the survey [67.8% of the patients had Crohn's disease], 49.9% were in clinical remission. The IBD-disk completion rate was 73.8%. The final analysis was conducted in this population [n = 1455 patients]. The mean IBD-disk score and IBD daily-life burden VAS were 39.0 ± 23.2 and 5.2 ± 2.9, respectively. The IBD-disk score was well correlated with the IBD daily-life burden VAS [r = 0.67; p <0.001]. At an optimal IBD-disk cut-off of 40, the area under the receiver operating characteristic curve [AUROC] for high IBD daily-life burden [VAS >5] was 0.81 (95% confidence interval [CI]: 0.79-0.83; p <0.001)., Conclusions: In a large cohort of patients, the IBD-disk score was well correlated with IBD daily-life burden, and it could be used in clinical practice., (© The Author(s) 2020. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Golimumab (GOL) is registered for moderate to severely active ulcerative colitis (UC). Data on the use of GOL in daily clinical practice are limited. Currently, it is unclear which factors are predictive of a favorable outcome. The goals of this study were to evaluate the mid-term outcome of GOL (week 26) in patients with moderate to severe UC and to determine predictors of favorable outcome., Methods: Patients included in the SMART study (NCT02155335) were evaluated for their mid-term outcome. Demographic data, disease characteristics, and medical history were recorded retrospectively. Data on disease activity based on total Mayo score, previous and concomitant medication, GOL dosing, mucosal healing (Mayo 0 or 1), adverse events (colectomy, hospitalization), and biomarkers (C-reactive protein, fecal calprotectin, hemoglobin, and albumin) were collected at baseline and weeks 2, 6, 14, 26, and 52. GOL was dosed at 200 and 100 mg at weeks 0 and 2, respectively, and 50 mg (<80 kg body weight) or 100 mg (≥80 kg body weight) every 4 weeks thereafter. The primary end point was steroid-free GOL continuation at week 26., Results: From the 91 evaluable patients (42% female; median age, 42 years; median disease duration, 5 years), 4% were active smokers, 25% had extensive colitis, and 38% had an endoscopic Mayo score of 3 at baseline. The median (interquartile range [IQR]) baseline Mayo score was 9 (8-10). Although 75% of patients had previously failed immunomodulators (IMMs), the majority (87%) were anti-tumor necrosis factor (TNF) naïve. GOL was started in combination with IMM in 40% and steroids in 64%. The median (IQR) duration of GOL therapy during follow-up was 35.7 (11.4-105.7) weeks. Twenty-six weeks after GOL induction, 37 patients (41%) were steroid-free and still on GOL, of whom 8 (21.6%) required GOL dose optimization. Short-term mucosal healing (STMH) at week 14 was evaluated in 60% of the patients. Considering the whole cohort, only 40% achieved STMH. No predictors could be retained of short-term treatment outcome. In multivariate analysis, STMH was predictive of steroid-free GOL continuation at week 26 (odds ratio [OR], 5.56; 95% confidence interval [CI], 1.90-16.29; P = 0.002) and week 52 (OR, 9.38; 95% CI, 2.68-32.84; P < 0.001). In patients continuing GOL after week 14, STMH was predictive of intervention-free survival (OR, 2.05; 95% CI, 1.09-3.86; P = 0.026) and discontinuation-free survival (OR, 3.47; 95% CI, 1.58-7.58; P = 0.002). During follow-up, 78% needed an intervention, 68% discontinued GOL, and 3 patients needed a colectomy., Conclusions: Real-life data confirm the moderate effectiveness of GOL on the mid-term in active UC, but therapeutic interventions are frequently needed. Short-term mucosal healing predicts a favorable outcome. 10.1093/ibd/izy219&#95;video1izy219.video15798038438001.

Background: Accelerated step-up or anti-tumor necrosis factor (TNF) before first remission is currently not recommended in pediatric Crohn's disease., Methods: Five-year follow-up data from a prospective observational cohort of children diagnosed with Crohn's disease in Belgium were analyzed. Disease severity was scored as inactive, mild, or moderate to severe. Remission or inactive disease was defined as sustained if lasting ≥2 years. Univariate analyses were performed between anti-TNF-exposed versus naive patients and anti-TNF before versus after first remission and correlations assessed with primary outcomes average disease severity and sustained remission., Results: A total of 91 patients (median [IQR] age 12.7 [10.9-14.8] yrs, 53% male) were included. Disease location was 12% L1, 23% L2, and 64% L3 with 76% upper gastrointestinal and 30% perianal involvement. Disease severity was 25% mild and 75% moderate to severe. Of 66 (73%) anti-TNF-exposed patients, 34 (52%) had accelerated step-up. Anti-TNF use was associated with age (13.1 [11.5-15.2] versus 11.8 [8.7-13.8] yrs; P < 0.05), L2 (29% versus 8%; P = 0.04), and average disease severity (1.7 [1.4-1.9] versus 1.4 [1.3-1.6]; P < 0.001). Duration of anti-TNF correlated with average disease severity (r = 0.32, P = 0.002). Accelerated step-up was also associated with age (13.3 [12.1-15.9] versus 12.5 [10.2-14.1]; P = 0.02) and average disease severity (1.8 [1.6-1.9] versus 1.6 [1.3-1.8]; P = 0.002). Duration of sustained remission was similar in all patients, and no serious infections, cancer, or deaths were reported., Conclusions: Anti-TNF therapy and accelerated step-up in older patients with more severe disease leads to beneficial long-term outcomes.

Background and Aims: Acute optic neuritis [ON] is an inflammatory condition affecting the optic nerve. Clinicians should suspect optic neuritis in cases of painful and rapidly progressive loss of central visual field. This condition may be associated with a multitude of diseases, and mostly with multiple sclerosis [MS] where it may present as an initial symptom. The literature reports that optic neuritis and MS occur in patients with inflammatory bowel disease [IBD] before and after the era of anti-tumour necrosis factor-α [TNFα] drugs. At the present moment, there is little consensus for managing this complication, currently treated with corticosteroids and discontinuation of the causative agents., Methods: We collected cases through a retrospective multicentre European Crohn's and Colitis Organisation CONFER [COllaborative Network For Exceptionally Rare case reports] project. We also performed a comprehensive retrospective search of the available literature on this topic., Results: We report herein 12 new cases of ON, including 10 under anti-TNF therapy, collected through the CONFER project. We also compare characteristics of ON associated or not with anti-TNFα agents., Conclusions: The exceptional and current observation of distant family history of MS in 17% of our patients who developed ON, despite the small number and the lack of a control arm, might be an important signal that should be taken into account in our therapeutic strategies in the future., (Copyright © 2016 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background and Aims: Anal fistula plug [AFP] is a bioabsorbable bioprosthesis used in ano-perineal fistula treatment. We aimed to assess efficacy and safety of AFP in fistulising ano-perineal Crohn's disease [FAP-CD]., Methods: In a multicentre, open-label, randomised controlled trial we compared seton removal alone [control group] with AFP insertion [AFP group] in 106 Crohn's disease patients with non- or mildly active disease having at least one ano-perineal fistula tract drained for more than 1 month. Patients with abscess [collection ≥ 3mm on magnetic resonance imaging or recto-vaginal fistulas were excluded. Randomisation was stratified in simple or complex fistulas according to AGA classification. Primary end point was fistula closure at Week 12., Results: In all, 54 patients were randomised to AFP group [control group 52]. Median fistula duration was 23 [10-53] months. Median Crohn's Disease Activity Index at baseline was 81 [45-135]. Fistula closure at Week 12 was achieved in 31.5% patients in the AFP group and in 23.1 % in the control group (relative risk [RR] stratified on AGA classification: 1.31; 95% confidence interval: 0.59-4.02; p = 0.19). No interaction in treatment effect with complexity stratum was found; 33.3% of patients with complex fistula and 30.8% of patients with simple fistula closed the tracts after AFP, as compared with 15.4% and 25.6% in controls, respectively [RR of success = 2.17 in complex fistula vs RR = 1.20 in simple fistula; p = 0.45]. Concerning safety, at Week 12, 17 patients developed at least one adverse event in the AFP group vs 8 in the controls [p = 0.07]., Conclusion: AFP is not more effective than seton removal alone to achieve FAP-CD closure., (Copyright © 2015 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Aim: A Belgian registry for pediatric Crohn's disease, BELCRO, was created. This first report aims at describing disease presentation and phenotype and determining associations between variables at diagnosis and registration in the database., Methods: Through a collaborative network, children with previously established Crohn's disease and newly diagnosed children and adolescents (under 18 y of age) were recruited over a 2 year period. Data were collected by 23 centers and entered in a database. Statistical association tests analyzed relationships between variables of interest at diagnosis., Results: Two hundred fifty-five patients were included. Median age at diagnosis was 12.5 y (range: 1.6-18 y); median duration of symptoms prior to diagnosis was 3 m (range: 1-12 m). Neonatal history and previous medical history did not influence disease onset nor disease behavior. Fifty three % of these patients presented with a BMI z-score < -1. CRP was an independent predictor of disease severity. Steroids were widely used as initial treatment in moderate to severe and extensive disease. Over time, immunomodulators and biological were prescribed more frequently, reflecting a lower prescription rate for steroids and 5-ASA. A positive family history was the sole significant determinant for earlier use of immunosuppression., Conclusion: In Belgium, the median age of children presenting with Crohn's disease is 12.5 y. Faltering growth, extensive disease and upper GI involvement are frequent. CRP is an independent predictive factor of disease activity. A positive family history appears to be the main determinant for initial treatment choice., (Copyright © 2013 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.)

Background: This study examined whether fecal calprotectin can be used in daily practice as a marker to monitor patients with ulcerative colitis (UC) receiving infliximab maintenance therapy., Methods: This prospective multicenter study enrolled adult patients with UC in clinical remission under infliximab maintenance therapy. Fecal calprotectin levels were measured every 4 weeks. Sigmoidoscopies were performed at inclusion and at study end. Relapse was defined as a clinical need for change in treatment or an endoscopic Mayo subscore of ≥2 at week 52. Sustained deep remission was defined as a partial Mayo score <3 at all points and an endoscopic Mayo score 0 at week 52., Results: Full analysis was possible for 87 of 113 included patients with UC (77%). Of these patients, 30 (34.4%) were considered to be in sustained deep remission and 13 (14.9%) to have relapsed. Calprotectin levels in patients with sustained deep remission remained very low (median < 40 mg/kg at all time points). Patients who flared had significantly higher calprotectin levels (median > 300 mg/kg) already 3 months before the flare. Further receiver operator curve analysis suggested that a calprotectin level >300 mg/kg had a reasonable sensitivity (58.3%) and specificity (93.3%) to model flare. Two consecutive calprotectin measurements of >300 mg/kg with 1-month interval were identified as the best predictor of flare (61.5% sensitivity and 100% specificity)., Conclusions: Fecal calprotectin can be used in daily practice to monitor patients with UC receiving infliximab maintenance therapy. Two consecutive measurements >300 mg/kg is more specific than a single measurement for predicting relapse.

Background and Aims: Adalimumab is efficacious in inducing and maintaining remission in Crohn's disease but dose escalation is needed in 30-40% after 1 year. Attempts for dose de-escalation have not been studied. This study aimed to assess the need for, predictors, and outcome of dose escalation and de-escalation in a large cohort of adalimumab treated Crohn's patients., Methods: All consecutive patients treated with open label adalimumab for active Crohn's disease from the participating centres were included in this cohort study. A detailed retrospective chart review was performed to look for possible factors predicting outcome., Results: Eighty four percent of 720 patients had a primary response and were followed up for a median of 14 months. Thirty four percent needed escalation after a median of 7 months (0-55 months). Multivariate predictors for dose escalation were the following: prior anti-TNF use (p<0.0001), no concomitant azathioprine or <3 m (p<0.02) and abnormal CRP at start (p<0.05). Dose escalation re-induced response for at least 6 months in 67%. Only abnormal CRP at start correlated with failure of dose escalation (p=0.02). Dose de-escalation was attempted in 54% and was successful in 63%. After a median follow-up of 14 m adalimumab was discontinued in 29% of patients., Conclusion: In this study real life nationwide cohort of Crohn's patients treated with adalimumab dose escalation was needed in 34% and was successful in 67%. Dose de-escalation was attempted in 54% and was successful in 63%. Overall 71% of patients maintained long term response on adalimumab., (Copyright © 2012 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.)

Aim: To evaluate the effect of infliximab induction therapy on calprotectin levels in patients with ulcerative colitis (UC)., Patients and Methods: In this prospective study 53 patients with active UC from 17 centers were treated with infliximab therapy (5 mg/kg) at baseline, week 2, and week 6. Faecal calprotectin was measured every week. Sigmoidoscopies were performed at baseline, week 6 and week 10., Results: Median calprotectin levels decreased from 1260 (IQR 278.5- 3418) at baseline to 72.5 (IQR 18.5 - 463) at week 10 (p<0.001). After 10 weeks, infliximab therapy induced endoscopic remission and a decrease in calprotectin to<50 mg/kg or at least a 80% decrease from baseline level in 58% of patients. A significant and steep decrease of calprotectin levels was seen at week 2 for patients with an endoscopic remission at week 10 as compared to patients who did not show a remission. (p<0.001). At week 10 an excellent correlation was found between endoscopic remission and clinical Mayo score reflected by an AUC of ROC analyses of 0.94 (0.87-1) and with calprotectin measurements (AUC 0.91 (0.81-1)) : all patients with calprotectin levels <50 mg/kg, and a normal clinical Mayo score (=0) were in endoscopic remission., Conclusions: Infliximab induces a fast and significant decrease of faecal calprotectin levels in anti-TNF naïve patients with ulcerative colitis predictive for remission of disease., (Copyright © 2011 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.)

Background: Up to 25% of inflammatory bowel disease (IBD) patients undergoing surgery with an ileal pouch-anal anastomosis (IPAA) will develop chronic pouchitis not responding to antibiotics. In case reports, thiopurine analogs and infliximab (IFX) have been proposed as effective therapy in this setting. We analyzed the long-term efficacy of IFX in Belgian patients with refractory pouch complications., Methods: We identified 28 IPAA patients who received IFX for refractory luminal inflammation (pouchitis and/or pre-pouch ileitis, n = 25) and/or pouch fistula (n = 7). Patients with elements of Crohn's disease after review of the colectomy specimen were excluded. Clinical response was defined as complete in case of cessation of diarrhea, blood loss, and abdominal pain, and as partial in case of marked clinical improvement. Fistula response was defined as complete in case of cessation and as partial in case of reduction of fistula drainage., Results: Eighty-two percent of patients were concomitantly treated with immunomodulatory agents. At week 10 following start of IFX, 88% of patients with refractory luminal inflammation showed clinical response (14 partial, 8 complete), while 6 patients (86%) showed fistula response (3 partial, 3 complete). The mPDAI dropped significantly from 9.0 (interquartile range [IQR] 8.0-10.0) to 4.5 (3.0-7.0) points (P < 0.001). After a median follow-up of 20 (7-36) months, 56% showed sustained clinical response while 3 out of 7 fistula patients showed sustained fistula response. Five patients needed permanent ileostomy., Conclusions: In this series, IFX was effective long-term in IPAA patients with refractory luminal inflammation and pouch fistula. These results warrant a prospective multicenter randomized controlled trial.

Background: Seventy percent of Crohn's disease (CD) patients exhibit anastomotic recurrence within 1 year after ileo-caecal surgery. Recent clinical trials suggest the beneficial use of probiotics in the control of intestinal inflammation in pouchitis and ulcerative colitis. This study is a multicenter clinical trial evaluating the efficacy of an oral administration of the probiotic LAl on early post-operative endoscopic recurrence of CD., Methods: Seventy patients with CD were enrolled prior to elective ileo-caecal resection and randomly assigned after surgery to daily treatment with either Lactobacillus johnsonii, LA1, Nestle (1010 colony-forming units, CFU) (group A, n = 34) or placebo (group B, n = 36) for 12 weeks. The primary objective was to assess the effect of LAl on the endoscopic recurrence rate at 12 weeks. Stratification was performed according to smoking status at randomization., Results: Seven and 14 patients were excluded in the LA1 and placebo groups, respectively. In intention-to-treat analysis, the mean endoscopic score was not significantly different between the two treatment groups at 3 months (LA1 versus placebo: 1.50 +/- 1.32 versus 1.22+/-1.37, treatment effect: P = 0.48, smoke effect: P = 0.72). The percentage of patients with severe recurrence (i3 + i4) was 21% and 15% in the LAl and placebo groups, respectively (P = 0.33). Using a per-protocol (PP) analysis, the mean endoscopic score was not significantly different between the two treatment groups (LAl versus placebo groups: 1.44 +/-1.31 versus 1.05 +/- 1.21, P = 0.32). The percentage of patients with severe recurrence (i3 + i4) was 19% and 9% in the LAl and placebo groups, respectively (P = 0.054). Clinical relapse rate (CDAI [CD activity index] > 150, with an increase of CDAI > 70 points or greater from baseline) in the LAl and placebo groups was 15% (4/27) and 13.5% (3/22), respectively (PP analysis: chi-square test, P = 0.91 and log-rank test: P = 0.79)., Conclusion: Oral administration of the probiotic LA1 in patients with CD failed to prevent early endoscopic recurrence at 12 weeks after ileo-caecal resection.