Efficacy and Safety of Ustekinumab for Chronic Pouchitis: A Prospective Open-label Multicenter Study.

BACKGROUND & AIMS: Seventeen percent of patients with ulcerative colitis that undergo proctocolectomy with pouch surgery will develop chronic pouchitis. We evaluated the efficacy of ustekinumab for these patients. METHODS: We performed a prospective study of patients with chronic pouchitis receiving ustekinumab intravenously at baseline (∼6 mg/kg) and 90 mg ustekinumab subcutaneously every 8 weeks thereafter. The Modified Pouchitis Disease Activity Index (mPDAI) was assessed at baseline and weeks 16 and 48. The primary endpoint was the proportion of patients achieving steroid-free remission (mPDAI <5 and reduction by ≥2 points) at week 16. Secondary endpoints included the proportion of patients achieving remission at week 48, the proportion of patients achieving response (reduction of mPDAI by ≥2 points) at weeks 16 and 48, and change in mPDAI. RESULTS: We enrolled 22 patients (59% male; median age, 42.2 years). Remission was achieved in 27.3% at week 16 and 36.4% at week 48. Response was achieved in 54.5% both at weeks 16 and 48. The median mPDAI decreased from 8 (interquartile range [IQR], 7-10) to 7 (IQR, 4-9) at week 16 (P = .007) and 4 (IQR, 1.75-7.25) at week 48 (P < .001). The clinical mPDAI subscore decreased from 3.5 (IQR, 2-4) to 2 (IQR, 1-3) at week 16 (P = .009) and 1 (IQR, 0-2.25) at week 48 (P = .001). The endoscopic mPDAI subscore decreased from 5.5 (IQR, 4-6) to 4 (IQR, 3-6) at week 16 (P = .032) and 3 (IQR, 1.75-4.25) at week 48 (P = .001). CONCLUSION: Ustekinumab was efficacious in one-half of the patients suffering from chronic pouchitis. Ustekinumab should therefore be positioned in the treatment algorithm of chronic pouchitis. (ClinicalTrials.gov Number NCT04089345).

Obesity in adult patients with inflammatory bowel disease: Clinical features and impact on disability. A cross-sectional survey from the GETAID.

BACKGROUND: In recent years, an increasing prevalence of obesity in inflammatory bowel disease (IBD) has been observed. However, only a few studies have focused on the impact of overweight and obesity on IBD-related disability. AIMS: To identify the factors associated with obese and overweight patients with IBD, including IBD-related disability. PATIENTS AND METHODS: In this cross-sectional study, we included 1704 consecutive patients with IBD in 42 centres affiliated with the Groupe d'Etude Therapeutique des Affections Inflammatoires du tube Digestif (GETAID) using a 4-page questionnaire. Factors associated with obesity and overweight were assessed using univariate and multivariate analyses (odds ratios (ORs) are provided with 95% confidence intervals). RESULTS: The prevalence rates of overweight and obesity were 24.1% and 12.2%, respectively. Multivariable analyses were stratified by age, sex, type of IBD, clinical remission and age at diagnosis of IBD. Overweight was significantly associated with male sex (OR = 0.52, 95% CI [0.39-0.68], p < 0.001), age (OR = 1.02, 95% CI [1.01-1.03], p < 0.001) and body image subscore (OR = 1.15, 95% CI [1.10-1.20], p < 0.001) (Table 2). Obesity was significantly associated with age (OR = 1.03, 95% CI [1.02-1.04], p < 0.001), joint pain subscore (OR = 1.08, 95% CI [1.02-1.14], p < 0.001) and body image subscore (OR = 1.25, 95% CI [1.19-1.32], p < 0.001) (Table 3). CONCLUSION: The increasing prevalence of overweight and obesity in patients with IBD is associated with age and poorer body image. A holistic approach to IBD patient care should be encouraged to improve IBD-related disability and to prevent rheumatological and cardiovascular complications.

Time trend in surgical indications and outcomes in ulcerative colitis-A two decades in-depth retrospective analysis.

BACKGROUND: Recent data regarding the impact of biologics and new surgical techniques on the indications and outcomes of colectomy for ulcerative colitis (UC) are limited. AIMS: The present study aimed at determining the trend of colectomy in UC by comparing colectomy indications and outcomes between 2000 and 2010 and 2011-2020. METHODS: This observational retrospective study was conducted in two tertiary hospitals, including consecutive patients who underwent colectomy between 2000 and 2020. All data concerning UC history, treatment and surgeries were collected. RESULTS: Among the 286 patients included, 87 underwent colectomy in 2001-2010 and 199 in 2011-2020. Patients' characteristics were similar between groups, except for prior biologic exposure (50.6 % vs. 74.9%; p<0.001). The indications of colectomy significantly decreased for refractory UC (50.6 % vs. 37.7%; p = 0.042), but were similar for acute severe UC (36.8 % vs. 42.2%; p = 0.390) and (pre)neoplastic lesions (12.6 % vs. 20.1%; p = 0.130). A widespread use of laparoscopy (47.7 % vs. 81.4%; p<0.001) was associated with fewer early complications (12.6 % vs. 5.5%; p = 0.038). CONCLUSION: Over the last two decades, the proportion of surgery for refractory UC significantly decreased compared to other surgical indications while surgical outcomes improved despite larger exposure to biologics.

Prevalence and Determinants of Fatigue in Patients with IBD: A Cross-Sectional Survey from the GETAID.

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.

Risk of SARS-CoV-2 infection in healthcare workers with inflammatory bowel disease: a case-control study.

Background: Whether healthcare workers with inflammatory bowel disease (IBD) are at increased risk of Novel coronavirus disease (COVID-19) due to occupational exposure is unknown. Aim: To assess the risk of COVID-19 in healthcare workers with IBD. Methods: A case control study enrolled 326 healthcare workers with IBD from 17 GETAID centres and matched non-healthcare workers with IBD controls (1:1) for gender, age, disease subtype and year of diagnosis. The study period was year 2020 during the COVID-19 outbreak. Results: In total, 59 COVID-19 were recorded among cases (n = 32) and controls (n = 27), including 2 severe COVID-19 (requiring hospitalization, mechanic ventilation) but no death. No difference was observed between healthcare workers and controls regarding the overall incidence rates of COVID-19 4.9 ± 2.2 vs. 3.8 ± 1.9 per 100 patient-semesters, P = 0.34) and the overall incidence rates of severe COVID-19 (0.6 ± 7.8 vs. 0.3 ± 5.5 per 100 patient-semesters, P = 0.42). In multivariate analysis in the entire study population, COVID-19 was associated with patients with body mass index > 30 kg/m2 (HR = 2.48, 95%CI [1.13-5.44], P = 0.02). Conclusion: Healthcare workers with IBD do not have an increased risk of COVID-19 compared with other patients with IBD.

Effect of 5-Hydroxytryptophan on Fatigue in Quiescent Inflammatory Bowel Disease: A Randomized Controlled Trial.

BACKGROUND & AIMS: Fatigue is highly prevalent among patients with inflammatory bowel disease (IBD), and only limited treatment options are available. Based on the hypothetical link between low serum tryptophan concentrations and fatigue, we determined the effect of 5-hydroxytryptophan supplementation on fatigue in patients with inactive IBD. METHODS: A multicenter randomized controlled trial was performed at 13 Belgian hospitals, including 166 patients with IBD in remission but experiencing fatigue, defined by a fatigue visual analog scale (fVAS) score of ≥5. Patients were treated in a crossover manner with 100 mg oral 5-hydroxytryptophan or placebo twice daily for 2 consecutive periods of 8 weeks. The primary end point was the proportion of patients reaching a ≥20% reduction in fVAS after 8 weeks of intervention. Secondary outcomes included changes in serum tryptophan metabolites, Functional Assessment of Chronic Illness Therapy Fatigue scale, and scores for depression, anxiety, and stress. The effect of the intervention on the outcomes was evaluated by linear mixed modeling. RESULTS: During 5-hydroxytryptophan treatment, a significant increase in serum 5-hydroxytryptophan (estimated mean difference, 52.66 ng/mL; 95% confidence interval [CI], 39.34-65.98 ng/mL; P < .001) and serotonin (3.0 ng/mL; 95 CI, 1.97-4.03 ng/mL; P < .001) levels was observed compared with placebo. The proportion of patients reaching ≥20% reduction in fVAS was similar in placebo- (37.6%) and 5-hydroxytryptophan (35.6%)-treated patients (P = .830). The fVAS reduction (-0.18; 95% CI, -0.81 to 0.46; P = .581) and Functional Assessment of Chronic Illness Therapy Fatigue scale increase (0.68; 95% CI, -2.37 to 3.73; P = .660) were both comparable between 5-hydroxytryptophan and placebo treatment as well as changes in depression, anxiety, and stress scores. CONCLUSIONS: Despite a significant increase in serum 5-hydroxytryptophan and serotonin levels, oral 5-hydroxytryptophan did not modulate IBD-related fatigue better than placebo. (Trial Registration: Belgian Federal Agency for Medication and Health Products, EudraCT number: 2017-005059-10 and ClinicalTrials.gov: NCT03574948, https://clinicaltrials.gov/ct2/show/NCT03574948.).

Long-Term Safety and Efficacy of Risankizumab Treatment in Patients with Crohn's Disease: Results from the Phase 2 Open-Label Extension Study.

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.

Patients' real-world experience with inflammatory bowel disease: A cross-sectional survey in tertiary care centres from the GETAID group.

BACKGROUND: Patients' experience with healthcare professionals could influence their clinical outcomes. AIMS: To assess inflammatory bowel disease (IBD) patients' experience with their disease, their treatment and their relationship with their physician. METHODS: A one-week cross-sectional study was conducted in 42 IBD centres. 2011 consecutive outpatients with IBD completed an anonymous self-report questionnaire assessing their experience with and knowledge of IBD. RESULTS: A quantitative assessment of the doctor-patient relationship revealed that patients' knowledge of IBD and IBD treatment ranged from 7.4 to 8.3 out of 10. In addition to IBD physicians, other sources of information about IBD and current treatment mainly included the internet (80% and 63%, respectively) and general practitioners (61% and 54%). Knowledge about education programmes (28%) was poor, resulting in a lack of willingness to further use these resources (25%). Concerns about IBD treatment were raised in 76% of patients, mostly related to the fear of adverse events (47%) and a lack of efficacy (33%). The need of alternative healthcare professionals was reported by 89% of the sample. CONCLUSION: In a large cohort of patients, we highlighted gaps in the management of patients with IBD regarding the need for higher-quality information and the implementation of alternative healthcare professionals.

Evolution of Endoscopic Lesions in Steroid-Refractory Acute Severe Ulcerative Colitis Responding to Infliximab or Cyclosporine.

BACKGROUND/AIMS: Few data on the evolution of endoscopic findings are available in patients with acute severe ulcerative colitis (ASUC). The aim of this study was to describe this evolution in a prospective cohort. METHODS: Patients admitted for a steroid-refractory ASUC and included in a randomized trial comparing infliximab and cyclosporine were eligible if they achieved steroid-free clinical remission at day 98. Flexible sigmoidoscopies were performed at baseline, days 7, 42 and 98. Ulcerative colitis endoscopic index of severity (UCEIS) and its sub-scores - vascular pattern, bleeding and ulceration/erosion - were post-hoc calculated. Global endoscopic remission was defined by a UCEIS of 0, and partial endoscopic remission by any UCEIS sub-score of 0. RESULTS: Among the 55 patients analyzed (29 infliximab and 26 cyclosporine), 49 (83%) had UCEIS ≥6 at baseline at baseline. Partial endoscopic remission rates were higher for bleeding than for vascular pattern and for ulcerations/erosions at day 7 (20% vs. 4% and 5% (n = 55); p = .004 and p=.04), for bleeding and ulceration/erosion than for vascular pattern at day 42 [63% and 65% vs. 33% (n=54); p<.001 for both] and at day 98 [78% and 92% vs. 56% (n = 50); p = .007 and p < .001]. Global endoscopic remission rates at day 98 were higher in patients treated with infliximab than with cyclosporine [73% vs. 25% (n = 26 and 24); p < .001]. CONCLUSION: In steroid-refractory ASUC patients responding to a second-line medical therapy, endoscopic remission process started with bleeding remission and was not achieved in half the patients at day 98 for vascular pattern. Infliximab provided a higher endoscopic remission rate than cyclosporine at day 98.

The IBD-disk Is a Reliable Tool to Assess the Daily-life Burden of Patients with Inflammatory Bowel Disease.

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.

Early Mucosal Healing Predicts Favorable Outcomes in Patients With Moderate to Severe Ulcerative Colitis Treated With Golimumab: Data From the Real-life BE-SMART Cohort.

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_video1izy219.video15798038438001.

Risk of serious infection in healthcare workers with inflammatory bowel disease: a case-control study of the Groupe d'Etude Thérapeutique des Affections Inflammatoires du tube Digestif (GETAID).

BACKGROUND: Whether healthcare workers with inflammatory bowel disease (IBD) are at increased risk of severe infection due to daily pathogen exposure is controversial. AIM: To assess the risk of severe infection in healthcare workers with IBD in a large multicentre case-control study. METHODS: The study population comprised 482 healthcare workers with IBD from 17 centres who were matched for gender, age, disease subtype and year of diagnosis to 482 controls (non-healthcare workers with IBD). The study period was between the date of diagnosis of IBD and June 2016. Severe infection was defined as any community-acquired infection that required hospitalisation. RESULTS: With a median follow-up of 9.3 years, 139 severe infections were recorded among cases and controls, including 30 Clostridium difficile infections, 33 severe viral infections, nine tuberculosis infections, 21 community-acquired pneumonia and 46 others. No difference was observed between healthcare workers and controls regarding the overall incidence rates of severe infection. An increased risk of tuberculosis was noted in healthcare workers. In multivariate analysis in the entire study population, severe infection was associated with current exposure to corticosteroids (OR = 3.05, 95% CI [2.06-4.52], P < 0.001), immunosuppressants (OR = 1.98, 95% CI [1.38-2.84], P < 0.001) and anti-TNF agents (OR = 2.93, 95% CI [2.02-4.27], P < 0.001) and reduced with Crohn's disease (OR = 0.63, 95% CI [0.43-0.91], P = 0.01). CONCLUSIONS: Healthcare workers with IBD do not have an increased risk of severe infection compared with other patients with IBD, except for tuberculosis. Screening for tuberculosis exposure should be assessed in this high-risk population when treated with anti-TNF agents.

Preference for a prefilled syringe or an auto-injection device for delivering golimumab in patients with moderate-to-severe ulcerative colitis: a randomized crossover study.

PURPOSE: Simponi® (golimumab, MSD) is a fully human monoclonal antibody against tumor necrosis factor alpha administered subcutaneously using an autoinjector or a prefilled syringe. This study examined preference for administration of golimumab by autoinjector or prefilled syringe in patients with moderate-to-severe ulcerative colitis (UC). PATIENTS AND METHODS: This was a multicenter, open-label, randomized crossover trial (EudraCT no 2014-000656-29). Patients with moderate-to-severe UC were randomized 1:1 to receive 2 subcutaneous injections of 50 mg golimumab with the autoinjector followed by 2 injections of 50 mg with the prefilled syringe or the same 4 injections administered in the opposite order. Patients assessed preference, ease of use, and discomfort immediately after the injections and 2 weeks later. RESULTS: Ninety-one patients were included (median age=42.7 years [range, 19.7-93.7]; 58% male). The autoinjector was preferred by 76.9% of patients immediately after injections and by 71.4% 2 weeks later. The autoinjector was more often considered extremely easy or easy to use (94.5%) than the prefilled syringe (73.6%). Moderate discomfort or worse was reported by more patients when using the prefilled syringe (20.9%) than when using the autoinjector (5.5%), and severe discomfort or discomfort preventing injection of future doses was reported by 8.8% for the pre-filled syringe but not at all when using the autoinjector. A favorable or extremely favorable overall impression was reported by 89.0% for the autoinjector and 72.5% for the prefilled syringe. CONCLUSION: Most patients with moderate-to-severe UC preferred to self-administer golimumab with the autoinjector over a prefilled syringe.

Risankizumab in patients with moderate to severe Crohn's disease: an open-label extension study.

BACKGROUND: Risankizumab, an anti-interleukin 23 antibody, was superior to placebo in achieving clinical and endoscopic remission at week 12 in a randomised, phase 2 induction study in patients with moderately to severely active Crohn's disease. Here we aimed to assess the efficacy and safety of extended intravenous induction and subcutaneous maintenance therapy with risankizumab. METHODS: All patients who completed the 12-week induction phase of the double-blind phase 2 induction study were included in this open-label extension study. Patients who did not achieve deep remission, defined as clinical remission (Crohn's Disease Activity Index [CDAI] <150) and endoscopic remission (Crohn's Disease Endoscopic Index of Severity [CDEIS] ≤4, or ≤2 for patients with isolated ileitis), at week 12 received open-label intravenous therapy with 600 mg risankizumab every 4 weeks for 12 weeks; patients in deep remission at week 12 entered a 12-week washout phase. Patients in clinical remission at week 26 were invited to participate in the maintenance phase of the study, in which they received open-label subcutaneous risankizumab (180 mg) every 8 weeks for 26 weeks. 26-week efficacy endpoints were the proportion of patients in clinical remission (CDAI <150), and the proportion of patients who achieved clinical response (either CDAI of <150 or a reduction from baseline of at least 100 points). 52-week efficacy endpoints were the proportion of patients achieving: clinical remission; clinical response; endoscopic response (>50% CDEIS reduction from baseline); endoscopic remission, as defined previously; mucosal healing; and deep remission. Safety was assessed in patients who received at least one dose of the study drug during the open-label phases of the study. This study is registered with ClinicalTrials.gov, number NCT02031276. FINDINGS: Of the 108 patients who completed the 12-week double-blind induction trial, six patients were in deep remission and entered the 12-week washout phase. 102 patients were not in deep remission, 101 of whom received 12 weeks of 600 mg risankizumab (33 from the original placebo group, 34 from the 200 mg risankizumab group, and 34 from the 600 mg risankizumab group); the other patient declined to continue the study. At week 26, 54 (53%) of 101 patients treated with 600 mg rizankizumab were in clinical remission. Among patients included in the open-label extension trial, clinical remission rates at week 26 versus week 12 were: 18 (55%) versus six (18%) of 33 patients in the original placebo group; 20 (59%) versus seven (21%) of 34 patients in the original 200 mg risankizumab group; and 16 (47%) versus nine (26%) of 34 patients in the original 600 mg risankizumab group. 62 patients received risankizumab maintenance treatment, including the 54 patients who achieved clinical remission at week 26, the six patients who had achieved deep remission at week 12, and one patient because of a protocol violation. At week 52, clinical remission was maintained in 44 (71%) patients; 50 (81%) patients had a clinical response, 22 (35%) patients were in endoscopic remission, and 34 (55%) patients had an endoscopic response. 15 (24%) patients had mucosal healing and 18 (29%) patients achieved deep remission at week 52. Risankizumab was well tolerated with no new safety signals noted. The most frequent treatment-emergent adverse events were arthralgia (25 [22%] of 115 patients), headache (23 [20%]), abdominal pain (21 [18%]), nasopharyngitis (18 [16%]), nausea (18 [16%]), and pyrexia (15 [13%]). Most adverse events were mild or moderate and considered to be unrelated to study treatment. There were no treatment-related deaths. INTERPRETATION: Extended induction treatment with open-label intravenous risankizumab was effective in increasing clinical response and remission rates at week 26. Open-label subcutaneous risankizumab maintained remission until week 52 in most patients who were in clinical remission at week 26. Selective blockade of interleukin 23 warrants further investigation as a treatment for Crohn's disease. FUNDING: Boehringer Ingelheim.

Efficacy of vedolizumab for induction of clinical response and remission in patients with moderate to severe inflammatory bowel disease who failed at least two TNF antagonists.

BACKGROUND: Vedolizumab is a recently available monoclonal antibody targeting α4ß7 integrin for the treatment of ulcerative colitis (UC) and Crohn's disease (CD). OBJECTIVE: The objective of this article is to evaluate the efficacy of vedolizumab induction therapy in anti-TNF-refractory/intolerant UC and CD patients in real life. METHODS: A cohort of 149 moderately to severely active UC and CD patients who failed or showed intolerance to at least two TNF antagonists participated in a medical need program and received vedolizumab in 37 Belgian centers (April-September 2015). Rates of clinical response and remission were retrospectively evaluated at Week 10 for UC and Week 14 for CD using the physician's global assessment (PGA), Mayo score and Harvey Bradshaw index (HBI) or Crohn's disease activity score (CDAI) scores. RESULTS: Eighty-four patients (29 UC, 55 CD) had sufficient data for analysis. For UC patients, clinical response was observed in 76% based on PGA and 59% based on the Mayo score. The corresponding percentages for CD patients were 80% for PGA and 65% for HBI/CDAI. Clinical remission rates were 10% and 40% for UC and CD, respectively. Steroid-free remission was observed in respectively 10% and 35%. Globally, corticosteroids were stopped in 14 out of 48 patients (29%). No new safety signals were reported. CONCLUSION: Up to 70% TNF-refractory/intolerant UC and CD patients achieved a clinical response after 10 to 14 weeks of vedolizumab treatment in this real-life cohort.

Long-term Outcomes with Anti-TNF Therapy and Accelerated Step-up in the Prospective Pediatric Belgian Crohn's Disease Registry (BELCRO).

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.

Induction therapy with the selective interleukin-23 inhibitor risankizumab in patients with moderate-to-severe Crohn's disease: a randomised, double-blind, placebo-controlled phase 2 study.

BACKGROUND: The interleukin-23 pathway is implicated genetically and biologically in the pathogenesis of Crohn's disease. We aimed to assess the efficacy and safety of risankizumab (BI 655066, Boehringer Ingelheim, Ingelheim, Germany), a humanised monoclonal antibody targeting the p19 subunit of interleukin-23, in patients with moderately-to-severely active Crohn's disease. METHODS: In this randomised, double-blind, placebo-controlled phase 2 study, we enrolled patients at 36 referral sites in North America, Europe, and southeast Asia. Eligible patients were aged 18-75 years, with a diagnosis of Crohn's disease for at least 3 months, assessed as moderate-to-severe Crohn's disease at screening, defined as a Crohn's Disease Activity Index (CDAI) of 220-450, with mucosal ulcers in the ileum or colon, or both, and a Crohn's Disease Endoscopic Index of Severity (CDEIS) of at least 7 (≥4 for patients with isolated ileitis) on ileocolonoscopy scored by a masked central reader. Patients were randomised 1:1:1 using an interactive response system to a double-blind investigational product, and stratified by previous exposure to TNF antagonists (yes vs no). Patients received intravenous 200 mg risankizumab, 600 mg risankizumab, or placebo, at weeks 0, 4, and 8. The primary outcome was clinical remission (CDAI <150) at week 12 (intention-to-treat population). Safety was assessed in patients who received at least one dose of study drug. This study is registered with ClinicalTrials.gov, number NCT02031276. FINDINGS: Between March, 2014, and September, 2015, 213 patients were screened, and 121 patients randomised. At baseline, 113 patients (93%) had been previously treated with at least one tumour necrosis factor (TNF) antagonist (which had failed in 96 [79%]). At week 12, 25 (31%) of 82 risankizumab patients (pooled 41 patients in 200 mg and 41 patients in 600 mg arms) had clinical remission versus six (15%) of 39 placebo patients (difference vs placebo 15·0%, 95% CI 0·1 to 30·1; p=0·0489). Ten (24%) of 41 patients who received 200 mg risankizumab had clinical remission (9·0%, -8·3 to 26·2; p=0·31) and 15 (37%) of 41 who received the 600 mg dose (20·9%, 2·6 to 39·2; p=0·0252). 95 (79%) patients had adverse events (32 in the placebo group, 32 randomised to 200 mg risankizumab, 31 randomised to 600 mg risankizumab); 18 had severe adverse events (nine, six, three); 12 discontinued (six, five, one); 24 had serious adverse events (12, nine, three). The most common adverse event was nausea and most common serious adverse event was worsening of underlying Crohn's disease. No deaths occurred. INTERPRETATION: In this short-term study, risankizumab was more effective than placebo for inducing clinical remission in patients with active Crohn's disease. Therefore, selective blockade of interleukin-23 via inhibition of p19 might be a viable therapeutic approach in Crohn's disease. FUNDING: Boehringer Ingelheim.

Management of a jejunal obstruction caused by the migration of a laparoscopic adjustable gastric banding. A case report.

INTRODUCTION: We present a rare case of jejunal obstruction due to the migration of a laparoscopic adjustable gastric band (LAGB) that occurred 10 years after surgery and was successfully treated by laparoscopy. This report is compliant with the SCARE guidelines. PRESENTATION OF CASE: A 42-year-old woman who underwent LAGB for morbid obesity 10 years ago was admitted with a small bowel obstruction due to the migration of a LAGB in the proximal small bowel. An attempt to endoscopic removal was unsuccessful and resulted in a laparoscopic extraction of the band. The post-operative course was uneventful. DISCUSSION: Formerly, LAGB was considered the safest technique in bariatric surgery. However, the rate of complication increases in long-term studies. When the IGM of the band is diagnosed, removal is the only issue. Small bowel obstruction caused by a migrated band appears to be a rare complication following IGM, and the only therapeutic option is surgery because an endoscopic procedure is not reliable. Furthermore, LAGB appears to be a less effective technique for weight loss than the sleeve gastrectomy and the gastric bypass. CONCLUSION: Small bowel obstruction caused by LAGB migration is a rare but serious complication following IGM. In such cases, endoscopy has to be avoided because of the risk of jejunal disruption. The only way to treat it properly is surgery. This type of late complication reinforces the interest in the techniques currently used in bariatric surgery such as sleeve gastrectomy and gastric bypass, providing also a better weight loss than the LAGB.