INTRODUCTION:The management of inflammatory bowel disease (IBD) in patients with cystic fibrosis (CF) at risk of respiratory failure and severe lung infection is poorly described. The objective of this study was to describe the phenotype and evolution of IBD associated with CF, as well as the efficacy and tolerance of IBD treatments. MATERIALS AND METHODS:A national, multicentre, descriptive, retrospective study was conducted. The study included all adult patients with a confirmed diagnosis of CF and IBD identified across participating GETAID centres. Disease characteristics and outcomes were retrieved from patient charts. RESULTS:A total of 10 cases with IBD associated with CF were identified (six male; median age at diagnosis, 32 years; 10 with Crohn's disease (CD)). In CF, the DeltaF508 mutation was predominant; nine patients had lung involvement, and all had exocrine pancreatic involvement. Disease location and behaviour at diagnosis were similar to those observed in the general IBD population. During follow-up, four patients underwent surgery (40%), and nine patients were treated with immunosuppressants or biologics, resulting in clinical remission for 50% and 66%, respectively. Two patients with severe CF co-colonised with Pseudomonas Aeruginosa and Staphylococcus aureus experienced severe lung infection. CONCLUSION:Patients with CF are more likely to have CD than ulcerative colitis. In patients with advanced CF, the potential infectious risks associated with IBD therapies require individualised assessment.

INTRODUCTION:Women with endometriosis have a higher risk of developing inflammatory bowel diseases (IBDs). This study aimed to better understanding the impact of endometriosis on the course of IBD. METHODS:We conducted a retrospective cohort study in 18 French and Belgian IBD centers between June 2022 and March 2023. Any patient with both conditions was eligible for inclusion. They were randomly matched to 1 or 2 patients with IBD without endometriosis. The impact on IBD progression was assessed using a composite severity criterion including intestinal damage or need for bowel surgery. RESULTS:Overall, 207 patients with both conditions (149 Crohn's disease [CD]; 58 ulcerative colitis [UC]) were matched to 409 patients with IBD alone. The median follow-up duration for IBD was 10 years (5.75-17). No difference was observed between the 2 groups regarding CD location, disease phenotype, and anoperineal involvement. Proctitis were more frequent in patients with UC and endometriosis. Patients with IBD with endometriosis were significantly less exposed to immunosuppressants (UC P < 0.01; CD P < 0.001) and biologics (UC P < 0.01; CD P < 0.001). Patients with CD with endometriosis had a less severe disease course compared with patients without endometriosis (hazard ratio 0.68, 95% confidence interval 0.50-0.92, P = 0.011). Patients with UC with endometriosis had not a significant different disease course compared with patients without endometriosis (hazard ratio 1.73, 95% confidence interval 0.74-4.00, P = 0.20). These results were similar in the subgroup of patients with endometriosis treated surgically. DISCUSSION:Endometriosis does not negatively influence the course of IBD, patients with CD even have a less severe progression. Patients were significantly less exposed to immunosuppressants and biologics.

Faecalibacterium has recently garnered attention for its potential health implications. To better understand its role, we developed and assessed real-time PCR assays for detecting and quantifying various Faecalibacterium species in human stool samples from both healthy individuals and Crohn's disease patients, either in flare or remission. The assays targeted the Microbial Anti-inflammatory Molecule (MAM) genes, which encode MAM proteins. These assays demonstrated 100% species-specificity using strains from six Faecalibacterium species: Faecalibacterium prausnitzii, Faecalibacterium taiwanense, Faecalibacterium duncaniae, Faecalibacterium longum, Faecalibacterium hattori, and Faecalibacterium CNCM4541. They also showed high sensitivity with detection limits of 10^5 bacteria per gram of sample. In healthy individuals, the different Faecalibacterium species varied in abundance. F. taiwanense, F. duncaniae, and F. longum were the most prevalent, around 10^10 bacteria/g of stool. In contrast, F. hattori and CNCM4541 were less abundant, with 10^7 bacteria/g. Despite its low abundance, F. hattori was present in all healthy subjects, while CNCM4541 was detected in only 50% of them. Notably, F. taiwanense, F. duncaniae, and F. longum were found in all healthy individuals. In Crohn's disease patients, both in flare and remission, a decrease in Faecalibacterium species was observed, with no recovery in remission. The most abundant species in Crohn's disease patients were F. prausnitzii and F. duncaniae, around 10^7 bacteria/g, while F. longum, F. hattori, and F. taiwanense were present at lower levels (10^6 bacteria/g), and CNCM4541 was no longer detected. Interestingly, F. prausnitzii showed a smaller decrease in abundance compared with other species. Moreover, F. prausnitzii was significantly more prevalent in patients in remission than in those in flare, suggesting that it may be more resistant to inflammation. These findings highlight the importance of accurately characterizing and quantifying Faecalibacterium species to better understand their role in health and disease.

Abstract Background Ileocecal resection (ICR) is a common procedure in Crohn’s disease (CD). Increasing evidence suggests ICR may be considered a first-line treatment for localized ileal CD to maintain long-term remission, rather than starting biologics. However, removal of the ileocecal valve affects bowel transit and disabling symptoms may arise. The aim of our study was to prospectively assess the impact of primary ICR on daily digestive symptoms in CD patients. Methods We included patients who underwent primary ICR at Saint-Antoine Hospital between January 2017 and December 2022. Patients were assessed after a morphological evaluation (endoscopy or MRI) performed between 5 months and 1 year post-ICR. Digestive symptoms were prospectively and systematically collected using a dedicated database. The primary endpoint was the prevalence of a composite outcome, defined as at least 4 soft or liquid stools per day and/or a fecal urgency with inability to delay defecation for more than 15 minutes, and/or moderate to severe daily abdominal pain. Secondary endpoints included other digestive symptoms. Multiple logistic regression analysis was performed to assess predictive factors for the primary outcome. Results One hundred nine patients were included. Indications for ICR were fistulizing disease (n=61, 56%) and stenosis (n=41, 37.6%). Only 7 patients (6.4%) had surgery for uncomplicated inflammatory disease. Thirty-five patients (32.1%) had morphological recurrence, defined as i2b, i3, i4 score, deep ulcers, stenosis, or fistulas on MRI. The primary endpoint was met by 24 patients (22%), with 21.1% having at least 3 liquid stools per day. Diarrhea (soft to liquid stools daily) was observed in 56.9%, fecal urgency in 22.9%, and abdominal pain in 32.1% (Figure 1). The primary endpoint prevalence was 17.6% in patients without morphological recurrence and 31.4% in those with recurrence (p=0.17) (Table 1). Multivariate analysis showed that age >40 years at surgery (OR=3.58 [95%CI 1.06-12.8] p=0.04), disease duration >2 years (OR=5.67 [95%CI 1.69-23.0] p=0.008), sepsis (fever >38.3°C within 7 days before surgery) (OR=8.06 [95%CI 1.68-44.2] p=0.01), and small bowel resection length >40 cm (OR=9.50 [95%CI 2.35-45.8] p=0.003) were associated with poorer digestive quality of life as defined by the primary composite endpoint. Conclusion The prevalence of digestive symptoms after primary ICR for CD is notable, regardless of disease recurrence. Advanced age, long disease duration, sepsis at surgery, and resection length were associated with disabling digestive symptoms. These results suggest that ICR leads to frequent and disabling digestive symptoms for many patients, which should be considered when proposing ICR.

Abstract Background Alterations in gut microbiota composition and functions are involved in the pathogenesis of Inflammatory Bowel Disease (IBD) and the role of specific bacterial taxa has been particularly pointed out. The role of microbiota-derived metabolites, including those produced from tryptophan, are major actors in host-microbiota interactions in health and in IBD. Large studies analyzing both gut microbiota and metabolomics data are scarce. Methods In the current study, we analyzed a total of 764 individuals from Saint Antoine Hospital cohort, including 447 patients with Crohn's disease (CD), 262 patients with Ulcerative Colitis (UC) and 55 healthy subjects. We performed shotgun metagenomic sequencing on fecal samples and integrated the results with deep clinical phenotyping and targeted metabolomics data encompassing 294 different molecules. Results We observed strong changes in the taxonomic composition and functional capabilities of the microbiota in CD and UC patients compared to healthy subjects. Besides disease itself, the most important drivers of microbiota composition were the disease location (Montreal classification), recent antibiotic treatment, disease activity (flare vs remission) and history of ileocecal resection. Interestingly, IBD diagnosis explained much more the variations of microbiota functions than taxonomy. The decrease in microbiota diversity was stronger in CD than in UC. In parallel to a decreased amount of Faecalibacterium in IBD, we also observed a decrease in the diversity of Faecalibacterium strains, with a stronger decrease in CD. Our multifactorial analysis revealed specific microbial taxa and functions affected by disease-related factors. We particularly identified many correlations between tryptophan metabolites and microbial abundance. Targeted gene analysis of tryptophan-related enzymes in metagenomes further supported these findings. A network analysis considering bacterial taxa and metabolites revealed profound alterations in IBD with some specificities between CD and UC. Conclusion We pointed out new microbiome and metabolome alterations associated with IBD, with some phenotype specificities. Overall, our findings provide crucial information and a substantial resource for understanding the interactions between the host and microbiome in the context of IBD.

Combined Percutaneous Transhepatic Lymphatic Embolization and Peroral Duodenal Mucosal Radiofrequency Ablation to Manage Protein-Losing EnteropathyJournal of Vascular and Interventional RadiologyPreviewPercutaneous transhepatic lymphatic embolization (PTLE) and peroral esophagogastroduodenoscopy (EGD) duodenal mucosal radiofrequency ablation (RFA) were performed to manage protein-losing enteropathy (PLE) in patients with congenital heart disease (CHD). Five procedures were performed in 4 patients (M/F = 3/1, median age: 49 years [range 31-71 years]). Transhepatic lymphangiography demonstrated abnormal peri-duodenal lymphatic channels. After methylene blue injection through transhepatic access, subsequent EGD evaluation showed methylene blue extravasation at various sites in the duodenal mucosa. Full-Text PDF

Objective The extent to which tryptophan (Trp) metabolism alterations explain or influence the outcome of inflammatory bowel diseases (IBDs) is still unclear. However, several Trp metabolism end-products are essential to intestinal homeostasis. Here, we investigated the role of metabolites from the kynurenine pathway. Design Targeted quantitative metabolomics was performed in two large human IBD cohorts (1069 patients with IBD). Dextran sodium sulphate-induced colitis experiments in mice were used to evaluate effects of identified metabolites. In vitro, ex vivo and in vivo experiments were used to decipher mechanisms involved. Effects on energy metabolism were evaluated by different methods including Single Cell mEtabolism by profiling Translation inHibition. Results In mice and humans, intestinal inflammation severity negatively correlates with the amount of xanthurenic (XANA) and kynurenic (KYNA) acids. Supplementation with XANA or KYNA decreases colitis severity through effects on intestinal epithelial cells and T cells, involving Aryl hydrocarbon Receptor (AhR) activation and the rewiring of cellular energy metabolism. Furthermore, direct modulation of the endogenous tryptophan metabolism, using the recombinant enzyme aminoadipate aminotransferase (AADAT), responsible for the generation of XANA and KYNA, was protective in rodent colitis models. Conclusion Our study identified a new mechanism linking Trp metabolism to intestinal inflammation and IBD. Bringing back XANA and KYNA has protective effects involving AhR and the rewiring of the energy metabolism in intestinal epithelial cells and CD4(+) T cells. This study paves the way for new therapeutic strategies aiming at pharmacologically correcting its alterations in IBD by manipulating the endogenous metabolic pathway with AADAT.

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.

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.

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 & PLUSMN; 2.2 vs. 3.8 & PLUSMN; 1.9 per 100 patient-semesters, P = 0.34) and the overall incidence rates of severe COVID-19 (0.6 & PLUSMN; 7.8 vs. 0.3 & PLUSMN; 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.(C) 2022 The Authors. Published by Elsevier Ltd on behalf of The Healthcare Infection Society. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Introduction There are currently no comparative data on the efficacy and safety of vedolizumab and ustekinumab in ulcerative colitis (UC) after anti-TNF therapy fails. Methods We retrieved the full datasets of two observational, multicentre, retrospective studies of patients with UC for whom anti-TNF therapy failed and the patients were then treated with either vedolizumab or ustekinumab. The outcomes included steroid-free clinical remission, clinical remission, treatment persistence, colectomy, hospitalization, and serious and infectious adverse events. Propensity scores weighted comparison was applied. Results In total, 121 patients were included in the vedolizumab group and 97 were included in the ustekinumab group. At week 14 and week 52, in the weighted cohort, no difference was found between vedolizumab and ustekinumab for steroid-free clinical remission (OR = 0.55 [0.21-1.41], p = .21 and 0.94 [0.40-2.22], p = .89, respectively). There was no difference between vedolizumab and ustekinumab for secondary outcomes such as clinical remission, hospitalization, UC-related surgery, treatment persistence and serious and infectious adverse events. Conclusion In patients with UC for whom anti-TNF therapy failed, no difference was found between vedolizumab and ustekinumab after propensity scores weighted comparison. Further studies are required to determine predictive factors of the efficacy of both biological agents.

Abstract Background In the context of the Sars-Cov2 pandemic, the management of patients with chronic diseases and/or receiving immunosuppressive drugs was of concern due to lack of data to dictate their management. The objectives of our study were to evaluate the characteristics and prognosis of COVID-19 among IBD patients and to study the factors associated with severe COVID-19. Methods We carried out a multicentre bispective study in 30 French GETAID centres. Participating centres were asked to report all consecutive COVID19 cases occurring in their IBD-cohort between March,1st and December,31st 2020. The cases had to be confirmed by a PCR test, or by a chest CT scan demonstrating COVID19 lesions. In addition to the baseline examination, patients were scheduled for a follow up visit within 3–6 months following their infection. Demographics, disease characteristics, treatments, and the clinical course of IBD were prospectively recorded. Severe COVID-19 was defined as admission to the hospital >1 day and/or use of oxygen therapy and/or death. Predictive factors for developing severe COVID-19 were explored using univariate and multivariate logistic regression. Results A total of 719 IBD patients with COVID 19 were included; 54.2% were women, median age was 42 years, 64.4% had Crohn’s disease (CD), and median disease duration was 10.8 years. 13.3% of the patients were active smokers;12.7% had a BMI>30. With respect to the treatment, 72(10%) patients were not on any IBD medication, 75(10.4%) were only receiving 5-ASA, 164(22.8%) received conventional immunosuppressants, and 509(70.8%) biologics.21.6% of the patients developed either diarrhoea in remitters, or an exacerbation of diarrhoea in active patients. IBD treatments were maintained unchanged, suspended or discontinued in 73.4%, 25.5%, and 1.1% of the patients. Over the follow-up period, 13.2% of the patients had a flare. A total of 68 patients developed severe COVID 19, 67(9.3%) were hospitalized for a median duration of 6 days, and 4(0.6%) patients died. In multivariate analysis, age > 50 years (OR: 2.0,CI:1.06–3.72; p=0.031), obesity (OR: 2.01,CI:1.05–4.09; p=0.037), and comorbidities (OR: 3.28,CI:1.76–6.09; p=0.0002) were factors associated with the occurrence of severe COVID 19; while immunomodulatory treatment (biologic and/or immunosuppressant) was a protective factor for developing severe COVID 19 (OR: 0.38,CI: 0.22–0.69; p=0.0012). Conclusion Rate of severe COVID 19 in this cohort of IBD patients was corresponding to the general population with similar risk factors for severity, i.e., age, obesity and comorbidities. Prescription of immunomodulators was protective against severe COVID 19, raising the hypothesis of their potential immunological effect on the immune storm phase of Sars-Cov2.

BACKGROUND:The first COVID-19 wave started in February 2020 in France. The influx of patients requiring emergency care and high-level technicity led healthcare professionals to fear saturation of available care. In that context, the multidisciplinary Ethics-Support Cell (EST) was created to help medical teams consider the decisions that could potentially be sources of ethical dilemmas.OBJECTIVES:The primary objective was to prospectively collect information on requests for EST assistance from 23 March to 9 May 2020. The secondary aim was to describe the Cell's functions during that period.RESEARCH DESIGN:This observational, real-time study of requests for Cell consultations concerned ethical dilemmas arising during a public health crisis. The EST created a grid to collect relevant information (clinical, patient's/designated representative's preferences and ethical principles strained by the situation), thereby assuring that each EST asked the same questions, in the same order.PARTICIPANTS AND RESEARCH CONTEXT:Only our university hospital's clinicians could request EST intervention.ETHICAL CONSIDERATIONS:The hospital Research Ethics Committee approved this study (no. CER-2020-107). The patient, his/her family, or designated representative was informed of this ethics consultation and most met with EST members, which enabled them to express their preferences and/or opposition.FINDINGS/RESULTS:33 requests (patients' mean age: 80.8 years; 29 had COVID-19: 24 with dyspnea, 30 with comorbidities). 17 Emergency Department solicitations concerned ICU admission, without reference to resource constraints; others addressed therapeutic proportionality dilemmas.DISCUSSION:Intervention-request motives concerned limited resources and treatment intensity. Management revolved around three axes: the treatment option most appropriate for the patient, the feasibility of implementation, and dignified care for the patient.CONCLUSIONS:COVID-19 crisis forced hospitals to envisage prioritization of ICU access. Established decision-making criteria and protocols do not enable healthcare professionals to escape ethical dilemmas. That acknowledgement highlights ethical risks, enhances the added-value of nursing and encourages all players to be vigilant to pursue collective deliberations to achieve clear and transparent decisions.

Objective The association of IgA vasculitis (IgAV) and IBD is rarely described, mainly during anti-TNF-alpha therapy. We aimed to describe the association of IgAV and IBD. Methods We retrospectively analysed the association of IgAV and IBD through the implication of the GETAID and FVSG networks. Characteristics of IBD and IgAV were collected using a standardized case report form. Results Forty-three cases were included. IBD [mainly Crohn's disease (CD) in 58%] preceded IgAV in 38 (88%), with median interval of 9.2 (IQR 5.4-15.4) years. In these 38 patients, at IgAV diagnosis, five (13%) had active IBD and 28 (74%) were treated with anti-TNF-alpha for a median duration of 31.5 (IQR 19-56) months. Main IgAV manifestations were purpura all patients (100%), joints in 20/35 (57%), renal in 15/35 (43%) and gastrointestinal in 11/35 (31%) involvement. IgAV was treated with glucocorticoids in 25 (66%), colchicine in six (16%), CYC in six (16%) and anti-TNF-alpha were discontinued in 15/28 (54%). No IgAV relapse occurred when TNF-alpha blockers were stopped, vs 23% in patients pursuing it. Conversely, five (33%) had IBD flare or complication after anti-TNF-alpha cessation vs one (8%) in those continuing biologics. Anti-TNF-alpha were resumed in six (40%), with subsequent IgAV relapse in four (67%). Conclusions This large cohort suggests that TNF-alpha blockers may promote the onset of IgAV in IBD. Discontinuation of anti-TNF-alpha was associated with vasculitis remission but increased risk of IBD relapses, whereas continuation of anti-TNF-alpha was associated with IBD remission but vasculitis relapse.

BACKGROUND AND AIMS:An expanding number of monogenic defects have been identified as causative of severe forms of very early-onset inflammatory bowel diseases [VEO-IBD]. The present study aimed at defining how next-generation sequencing [NGS] methods can be used to improve identification of known molecular diagnosis and to adapt treatment. METHODS:A total of 207 children were recruited in 45 paediatric centres through an international collaborative network [ESPGHAN GENIUS working group] with a clinical presentation of severe VEO-IBD [n = 185] or an anamnesis suggestive of a monogenic disorder [n = 22]. Patients were divided at inclusion into three phenotypic subsets: predominantly small bowel inflammation, colitis with perianal lesions, and colitis only. Methods to obtain molecular diagnosis included functional tests followed by specific Sanger sequencing, custom-made targeted NGS, and in selected cases whole exome sequencing [WES] of parents-child trios. Genetic findings were validated clinically and/or functionally. RESULTS:Molecular diagnosis was achieved in 66/207 children [32%]: 61% with small bowel inflammation, 39% with colitis and perianal lesions, and 18% with colitis only. Targeted NGS pinpointed gene mutations causative of atypical presentations, and identified large exonic copy number variations previously missed by WES. CONCLUSIONS:Our results lead us to propose an optimised diagnostic strategy to identify known monogenic causes of severe IBD.

SummaryBackgroundPhase III trials have demonstrated the efficacy and safety of ustekinumab in moderate‐to‐severe ulcerative colitis (UC), but few real‐world data are currently available.AimTo assess short‐term effectiveness and safety of ustekinumab in patients with UC.MethodsFrom January to September 2019, all patients with UC treated with ustekinumab in 20 French GETAID centres were retrospectively included. The primary outcome was steroid‐free clinical remission (partial Mayo Clinic score ≤2) at weeks 12‐16 without a rectal bleeding subscore >1.ResultsAmong the 103 patients included, 70% had been previously exposed to ≥2 anti‐TNF agents and 85% to vedolizumab. At weeks 12‐16, steroid‐free clinical remission and clinical remission rates were 35.0% and 39.8% respectively; the absence of rectal bleeding with normal stool frequency was noted in 19.4% of patients. Two patients discontinued ustekinumab before the week 12‐16 visit and underwent surgery. In multivariable analysis, a partial Mayo Clinic score >6 at inclusion (18.6% vs 46.7%, P = 0.003) and a history of both exposure to anti‐TNF and vedolizumab therapies (27.3% vs 80.0%, P = 0.001) were negatively associated with steroid‐free clinical remission at weeks 12‐16. Adverse events occurred in 7.8% of patients and serious adverse events in 3.9% of patients.ConclusionIn a cohort of highly refractory patients with UC with multiple prior drug failures, ustekinumab provided steroid‐free clinical remission in one‐third of cases at weeks 12‐16. Clinical severity and previous use of anti‐TNF and vedolizumab therapies were associated with ustekinumab failure at weeks 12‐16.

SummaryBackgroundThe burden of inflammatory bowel disease (IBD) is rising worldwide. The goal of IBD treatment is to achieve clinical and endoscopic remission but also prevent disability.AimsTo identify the predictive factors of disability in a large population of patients with IBD.Patients and methodsWe conducted a cross‐sectional survey in 42 tertiary centres in France and Belgium. A self‐administered questionnaire was designed to explore patients and their IBD characteristics. IBD‐disk is a validated tool to measure disability in patients with IBD. The IBD‐disk score was then calculated for each patient. Based on a previous study, an overall IBD‐disk score ≥40 was associated with moderate‐to‐severe disability.ResultsAmong the 2011 patients, 1700 were analysed, including 746 (44%) in self‐reported clinical remission and 752 (44.2%) declaring clinical activity. The patient global assessment of global remission was missing in 200 (11.8%) of 1700 patients. Moderate‐to‐severe disability was significantly increased in patients with BMI >25 kg/m2 (OR = 1.66; 95% CI [1.29‐2.14]), in those having perception of need for a psychotherapist (OR = 2.24; 95% CI [1.79‐3.05]) and social worker (OR = 1.54; 95% CI [1.08‐2.21]). Conversely, male gender (OR = 0.83; 95% CI [0.69‐0.99]), ulcerative colitis (OR = 0.69; 95% CI [0.53‐0.92]), self‐reported clinical remission (OR = 0.59; 95% CI [0.46‐0.77]) and employed or student occupational status (OR = 0.69; 95% CI [0.52‐0.92]) were inversely correlated with disability. Overall, 257 (34.5%) patients who declared being in clinical remission had disability.ConclusionDeterminants of IBD‐related disability include IBD‐related factors but also psychological and social factors. This highlights the importance of a multidisciplinary team in the management of patients with IBD.