Confocal laser endomicroscopy as predictive biomarker of clinical and endoscopic efficacy of vedolizumab in ulcerative colitis: The DETECT study.

AIMS: In patients with ulcerative colitis (UC), no biomarker is available to help the physician to choose the most suitable biotherapy. The primary objective of this pilot study was to assess the feasibility of identification of α4ß7- and TNF-expressing cells, to predict the response to vedolizumab using confocal laser endoscopy (CLE). METHODS: Patients with moderate-to-severe UC, naïve of biotherapy, received vedolizumab. Clinical evaluation was performed at each infusion. Endoscopic evaluation was performed before inclusion and at week 22. Fresh colonic biopsies were stained using FITC-labelled vedolizumab and Alexa fluor-labelled adalimumab and ex vivo dual-band CLE images were acquired. Blood samples were collected to measure trough concentrations of vedolizumab and to determine absolute counts of T and B cells subpopulations, NK cells and monocytes. RESULTS: Nineteen patients were enrolled in the study and received at least one dose of vedolizumab. Clinical remission and endoscopic improvement were observed in 58% of whom 5 patients (45%) had an endoscopic subscore of 0. In terms of clinical response and remission, endoscopic improvement and histologic response, FITC-conjugated vedolizumab staining tended to be higher in responder patients compared to non-responders at week 22. A threshold value of 6 positive FITC-vedolizumab staining areas detected by CLE seemed informative to discriminate the responders and non-responders. The results were similar in terms of clinical remission and endoscopic improvement with a sensitivity of 78% and a specificity of 85% (p = 0.05). Trough concentrations and blood immune cells were not associated with responses to vedolizumab. CONCLUSION: This pilot study demonstrate that dual-band CLE is feasible to detect α4ß7- and TNF-expressing cells. Positive α4ß7 staining seems to be associated with clinical and endoscopic remission in UC patients treated by anti-α4ß7-integrin, subject to validation by larger-scale studies. Clinical-trial.gov: NCT02878083.

Discontinuation of Anti-Tumour Necrosis Factor Therapy in Patients with Perianal Fistulizing Crohn's Disease: Individual Participant Data Meta-Analysis of 309 Patients from 12 Studies.

BACKGROUND: The risk of relapse after anti-tumour necrosis factor [TNF] therapy discontinuation in Crohn's disease patients with perianal fistulas [pCD] is unclear. We aimed to assess this risk. METHODS: A systematic literature search was conducted to identify cohort studies on the incidence of relapse following anti-TNF discontinuation in pCD patients. Individual participant data were requested from the original study cohorts. Inclusion criteria were age ≥16 years, pCD as a (co)indication for start of anti-TNF therapy, more than three doses, and remission of luminal and pCD at anti-TNF discontinuation. The primary outcome was the cumulative incidence of CD relapse using Kaplan-Meier estimates. Secondary outcomes included response to re-treatment and risk factors associated with relapse as assessed by Cox regression analysis. RESULTS: In total, 309 patients from 12 studies in ten countries were included. The median duration of anti-TNF treatment was 14 months [interquartile range 5.8-32.5]. Most patients were treated for pCD without active luminal disease [89%], received first-line anti-TNF therapy [87%], and continued immunomodulatory therapy following anti-TNF discontinuation [78%]. The overall cumulative incidence of relapse was 36% (95% confidence interval [CI] 25-48%) and 42% [95% CI 32-53%] at 1 and 2 years after anti-TNF discontinuation, respectively. Risk factors for relapse included smoking (hazard ratio [HR] 1.5 [1.0, 2.1]) and history of proctitis (HR 1.7 [1.1, 2.5]). The overall re-treatment response rate was 82%. CONCLUSIONS: This individual participant data meta-analysis, on predominantly patients with pCD without active luminal disease and first-line anti-TNF therapy, shows that over half of patients remain in remission 2 years after anti-TNF discontinuation. Therefore, anti-TNF discontinuation may be considered in this subgroup.

Tofacitinib for Patients with Anti-TNF Refractory Ulcerative Proctitis: A Multicentre Cohort Study from the GETAID.

BACKGROUND: Although ulcerative proctitis [UP] can dramatically impair quality of life, treatment efficacy has been poorly investigated in UP as it was historically excluded from phase 2/3 randomised controlled trials in ulcerative colitis. Our aim was to assess the effectiveness and safety of tofacitinib for the treatment of UP. METHODS: We conducted a retrospective, multicentre study in 17 GETAID centres, including consecutive patients with UP treated with tofacitinib. The primary endpoint was steroid-free remission between Week 8 and Week 14, defined as a partial Mayo score of 2 [and no individual subscore above 1]. Secondary outcomes included clinical response and steroid-free remission after induction and at 1 year. RESULTS: All the 35 enrolled patients previously received anti-tumour necrosis factor [TNF] therapy and 88.6% were exposed to at least two lines of biologics. At baseline, the median partial Mayo score was 7 (intequartile range [IQR] [5.5-7]). After induction [W8-W14], 42.9% and 60.0% of patients achieved steroid-free remission and clinical response, respectively. At 1 year, the steroid-free clinical remission and clinical response rates were 39.4% and 45.5%, respectively, and 51.2% [17/33] were still receiving tofacitinib treatment. Survival without tofacitinib withdrawal was estimated at 50.4% (95% confidence interval [CI] [35.5-71.6]) at 1 year. Only a lower partial Mayo at baseline was independently associated with remission at induction (0dds ratio [OR] = 0.56 for an increase of 1, (95% CI [0.33-0.95], p = 0.03). Five [14.3%] adverse events were reported, with one leading to treatment withdrawal [septic shock secondary to cholecystitis]. CONCLUSION: Tofacitinib may offer a therapeutic option for patients with refractory UP.

Allogenic stem cells for Crohn's anal fistulas: Treating early improves the deep remission rate.

AIM: The aim of this study was to evaluate the real-life clinical and radiological efficacy of darvadstrocel injection into complex perianal fistulas in Crohn's disease. Secondary endpoints were to assess symptomatic efficacy, adverse effects and factors associated with complete combined clinical-radiological response (deep remission). METHODS: After marketing the product in France, all first patients treated consecutively were included. A complete clinical response was defined by a complete closure of all external openings with no discharge on pressure. A complete radiological response (MRI), evaluated at least after six months of follow-up, was defined by a completely fibrotic sequela without abscess. A deep remission was defined as the association of a complete clinical response with a complete radiological response. RESULTS: A total of 43 patients were included (M/F: 22/21, median age 37 [26-45] years). The fistulas were already drained with seton(s) and were on biologic treatment. After a median follow-up of 383 (359-505) days, 28 (65%) patients showed a clinical response (22 complete and 6 partial) and 16 (37%) achieved a deep remission. The Perineal Disease Activity Index decreased significantly after treatment: 39 (91%) patients reported symptomatic improvement in terms of discharge, pain, and induration, and 28 (65%) no longer had any perineal symptoms. No severe adverse events were reported. A short history of Crohn's disease <3 years was significantly associated with deep remission (OD 4.5 [1.0-19.1], p = 0.04). CONCLUSION: Darvadstrocel injection resulted in a clinical response for two thirds of patients and deep remission for one third. A shorter duration of Crohn's disease was associated with deep remission.

The risk of COVID-19 in IBD patients is increased by urban living and is not influenced by disease activity or intravenous biologics.

Background: Patients with inflammatory bowel disease (IBD) may have a modified immune response to SARS-CoV-2. The objectives were to evaluate the prevalence of COVID-19 in patients treated with infliximab or vedolizumab, to analyze the factors associated with the infection, the impact of treatments and trough levels. Methods: Patients with IBD treated with intravenous biologics in 14 French centers were included between March and June 2020 and followed-up for 6 months. Blood samples were collected for serologies and trough levels. The analysis of factors associated with COVID-19 was conducted in a matched 1:1 case-control sub-study with positive patients. Results: In total, 1026 patients were included (74.9% infliximab). Over the follow-up period, 420 patients reported the occurrence of COVID-19 symptoms; 342 had been tested of whom 18 were positive. At the end of follow-up, 38 patients had a positive serology. Considering both nasal tests and serologies together, 46 patients (4.5%) had been infected. The risk of COVID-19 was related neither to the use of treatments (whatever the trough levels) nor to disease activity. Infections were more frequent when using public transport or living in flats in urban areas. Conclusions: The prevalence rate of COVID-19 in this IBD population treated with intravenous infliximab or vedolizumab was the same as the one in the French population before the start of the vaccination campaign. The risk was increased by urban living and was not influenced by disease activity or biologics. Sanitary barrier measures remain the best way to protect against SARS-CoV-2 in patients with IBD in biological therapy.

Prevalence of and Factors Associated With Extraintestinal Manifestations and Their Remission in Inflammatory Bowel Disease: The EXTRA-Intestinal Manifestation Prospective Study From the Groupe d'Etude Thérapeutique des Affections Inflammatoires du Tube Digestif.

INTRODUCTION: Extraintestinal manifestations (EIMs) of inflammatory bowel disease (IBD) are challenging clinical situation. No prospective study assessed remission risk factors of EIMs. The aim of this study was to prospectively investigate the epidemiology, risk factors of EIM occurrence, and EIM remission in a large IBD cohort. METHODS: We conducted a cross-sectional study in 30 French referral centers. Between May 2021 and June 2021, all consecutive patients attending to hospital appointment were systematically invited to fill out a questionnaire. RESULTS: A total of 1,971 consecutive patients with IBD were analyzed. There were 1,056 women (53.8%), and the median age of patients was 41 years (31-54). The median disease duration was 11 years (1-18). Overall, 544 (27.6%) had at least 1 EIM. In 20.2% of cases, patients had multiple EIMs. The most frequent EIMs were rheumatological (19%) and dermatological (10%) manifestations. Immunosuppressant treatment (odds ratio [OR] = 2.56; P < 0.001) was a risk factor of EIM, while the Montreal A3 classification (OR = 0.61, P = 0.023) and male gender (OR = 0.61, P < 0.001) were associated with a lower risk of EIM occurrence. IBD current clinical remission (OR = 2.42; P < 0.001) and smoking cessation (OR = 2.98; P < 0.001) were associated factors of EIM remission. Conversely, age at IBD diagnosis (OR = 0.98; P < 0.018) was associated with a lower risk of EIM remission. DISCUSSION: One quarter of patients had at least 1 EIM. Beyond factors associated with the presence of EIMs, patients with IBD current clinical remission and smoking cessation are more likely to achieve EIM remission, while increasing age at IBD diagnosis is associated with decreased chance of remission.

Mitochondrial remodeling and energy metabolism adaptations in colonic crypts during spontaneous epithelial repair after colitis induction in mice.

Mucosal healing has emerged as a therapeutic goal to achieve lasting clinical remission in ulcerative colitis. Intestinal repair in response to inflammation presumably requires higher energy supplies for the restoration of intestinal barrier and physiological functions. However, epithelial energy metabolism during intestinal mucosal healing has been little studied, whereas inflammation-induced alterations have been reported in the main energy production site, the mitochondria. The aim of the present work was to assess the involvement of mitochondrial activity and the events influencing their function during spontaneous epithelial repair after colitis induction in mouse colonic crypts. The results obtained show adaptations of colonocyte metabolism during colitis to ensure maximal ATP production for supporting energetic demand by both oxidative phosphorylation and glycolysis in a context of decreased mitochondrial biogenesis and through mitochondrial function restoration during colon epithelial repair. In parallel, colitis-induced mitochondrial ROS production in colonic epithelial cells was rapidly associated with transient expression of GSH-related enzymes. Mitochondrial respiration in colonic crypts was markedly increased during both inflammatory and recovery phases despite decreased expression of several mitochondrial respiratory chain complex subunits after colitis induction. Rapid induction of mitochondrial fusion was associated with mitochondrial function restoration. Finally, in contrast with the kinetics expression of genes involved in mitochondrial oxidative metabolism and in glycolysis, the expression of glutaminase was markedly reduced in the colonic crypts both during colitis and repair phases. Overall, our data suggest that the epithelial repair after colitis induction is characterized by a rapid and transient increased capacity for mitochondrial ATP production in a context of apparent restoration of mitochondrial biogenesis and metabolic reorientation of energy production. The potential implication of energy production adaptations within colonic crypts to sustain mucosal healing in a context of altered fuel supply is discussed.

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.

Preoperative Predictors of Neoplasia in Patients Undergoing Small Bowel Resection for Complicated Crohn's Disease: A Multicentre Case-Control Study.

Crohn's disease (CD) is associated with an increased risk of small bowel neoplasia (SBN). We aimed to assess preoperative predictors of SBN in CD patients. We conducted a retrospective case-control study including CD patients who underwent surgery: cases were diagnosed with SBN on histopathological analysis and controls had no neoplasia. Preoperative cross-sectional imaging was reviewed by a panel of blinded expert radiologists. Fifty cases were matched to one hundred and fifty consecutive controls. In multivariable analysis, predictors of SBN were age ≥ 50 years (OR = 28, 95% CI = 5.05-206), median CD duration ≥ 17.5 years (OR = 4.25, 95% CI = 1.33-14.3), and surgery for stricture (OR = 5.84, 95% CI = 1.27-35.4). The predictors of small bowel adenocarcinoma were age ≥ 50 years (OR = 5.14, 95% CI = 2.12-12.7), CD duration ≥ 15 years (OR = 5.65, 95% CI = 2.33-14.3), and digestive wall thickening > 8 mm (OR = 3.79, 95% CI = 1.45-11.3). A predictive score based on the aforementioned factors was constructed. Almost 73.7% of patients with a high score had SBA. Old age, long small bowel CD duration, and stricture predicted the presence of SBN, particularly adenocarcinoma when patients have digestive wall thickening > 8 mm on preoperative imaging.

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.

Comparative Acceptability of Therapeutic Maintenance Regimens in Patients With Inflammatory Bowel Disease: Results From the Nationwide ACCEPT2 Study.

BACKGROUND: Owing to growing number of therapeutic options with similar efficacy and safety, we compared the acceptability of therapeutic maintenance regimens in inflammatory bowel disease (IBD). METHODS: From a nationwide study (24 public or private centers), IBD patients were consecutively included for 6 weeks. A dedicated questionnaire including acceptability numerical scales (ANS) ranging from 0 to 10 (highest acceptability) was administered to both patients and related physicians. RESULTS: Among 1850 included patients (65.9% with Crohn's disease), the ANS were 8.68 ± 2.52 for oral route (first choice in 65.8%), 7.67 ± 2.94 for subcutaneous injections (first choice in 21.4%), and 6.79 ± 3.31 for intravenous infusions (first choice in 12.8%; P < .001 for each comparison). In biologic-naïve patients (n = 315), the most accepted maintenance regimens were oral intake once (ANS = 8.8 ± 2.2) or twice (ANS = 6.9 ± 3.4) daily and subcutaneous injections every 12 or 8 weeks (ANS = 7.9 ± 3.0 and ANS = 7.2 ± 3.2, respectively). Among 342 patients with prior exposure to subcutaneous biologics, the preferred regimens were subcutaneous injections (≥2 week-intervals; ANS between 9.1 ± 2.3 and 8.1 ± 2.7) and oral intake once daily (ANS = 7.7 ± 3.2); although it was subcutaneous injections every 12 or 8 weeks (ANS = 8.4 ± 3.0 and ANS = 8.1 ± 3.0, respectively) and oral intake once daily (ANS = 7.6 ± 3.1) in case of prior exposure to intravenous biologics (n = 1181). The impact of usual therapeutic escalation or de-escalation was mild (effect size <0.5). From patients' acceptability perspective, superiority and noninferiority cutoff values should be 15% and 5%, respectively. CONCLUSIONS: Although oral intake is overall preferred, acceptability is highly impacted by the rhythm of administration and prior medication exposures. However, SC treatment with long intervals between 2 injections (≥8 weeks) and oral intake once daily seems to be the most accepted modalities.

Considering both the route of medication delivery and the interval between 2 administrations, we observed a strong impact of patients' experience regarding previous treatments. The most accepted maintenance regimens were subcutaneous injections with interval ≥8 weeks and oral intake.

Identification of the optimal medical and surgical management for patients with perianal fistulising Crohn's disease.

AIM: The aim of our study was to assess the best medical and surgical approaches for perianal Crohn's disease (PCD) in order to identify an optimal combined medical and surgical treatment. METHODS: Medical records of all patients with PCD treated with TNFα antagonists in two referral centres between 1998 and 2018 were reviewed. Predictors of long-term outcomes were identified using a Cox proportional hazard model. RESULTS: A total of 200 patients were included. Fifty-three patients (26.5%) were treated with adalimumab and 147 (73.5%) with infliximab. A combination of TNFα antagonist with an immunosuppressant and the presence of proctitis were independently associated with fistula closure. Seton was placed in 127 patients (63.5%) before starting biological therapy. Eighty patients (40%) underwent additional perineal surgery. Prior PCD surgery, seton positioning, additional perineal surgery, and additional surgery within 52 weeks of anti-TNFα treatment were associated with an increased rate of fistula closure. Finally, medical combination therapy (anti-TNFα plus immunosuppressant) along with seton placement and additional surgery within 1 year was the best management for PCD patients (p = 0.02). CONCLUSION: Combined medical and surgical management is required for the treatment of PCD patients. Medical combination therapy associated with seton placement and additional surgery within 1 year is the best management for PCD patients.

Efficacy and safety of combination targeted therapies in immune-mediated inflammatory disease: the COMBIO study.

BACKGROUND: Use of a combination of targeted therapies (COMBIO) in patients with refractory/overlapping immune-mediated inflammatory diseases (IMIDs) has increased, but reported data remain scarce. We aimed to assess effectiveness and safety of COMBIO in patients with IMIDs. METHODS: We conducted a French ambispective multicenter cohort study from September 2020 to May 2021, including adults' patients with 1 or 2 IMIDs and treated at least 3-month with COMBIO. RESULTS: Overall, 143 patients were included. The most common IMIDs were Crohn's disease (63.6%), axial spondyloarthritis (37.7%), and ulcerative colitis (14%). Half of patients had only one IMID, of which 60% were Crohn's disease. Mean duration of COMBIO was 274.5±59.3 weeks, and COMBIO persistence at 104 weeks was estimated at 64.1%. The most frequent COMBIOs combined anti-TNF agents with vedolizumab (30%) or ustekinumab (28.7%). Overall, 50% of patients achieved significant and 27% mild-to-moderate improvement in patient-reported outcomes. Extended duration of COMBIO (aOR=1.09; 95% CI: 1.03-1.14; p=0.002) and diagnoses of two IMIDs (aOR=3.46; 95%CI: 1.29-9.26; p=0.013) were associated with significant improvement in patient-reported outcomes. Incidence of serious infection during COMBIO was 4.51 per 100 person-years (95% CI 2.20-8.27) and 5 COMBIOs were discontinued due to adverse events. CONCLUSIONS: COMBIO can be effective and safe in patients with refractory/overlapping IMIDs.

Real-world comparison of effectiveness between tofacitinib and vedolizumab in patients with ulcerative colitis exposed to at least one anti-TNF agent.

BACKGROUND: Data comparing tofacitinib and vedolizumab in ulcerative colitis (UC) are lacking. AIMS: To compare the effectiveness of tofacitinib and vedolizumab in patients with UC who had prior exposure to anti-TNF therapy METHODS: In this multicentre study, we included consecutive patients with UC ≥18 years old with partial Mayo score >2 and prior anti-TNF exposure, who started tofacitinib or vedolizumab between January 2019 and June 2021. Comparisons were performed using propensity score analyses (inverse probability of treatment weighting). RESULTS: Overall, 126 and 178 patients received tofacitinib and vedolizumab, respectively. Intensified induction (vedolizumab infusion at week 10 or tofacitinib 10 mg b.d until week 16) was performed in 28.5% and 41.5% of patients, respectively. After propensity-score analysis, corticosteroid-free clinical remission (partial Mayo score ≤2) was achieved at week 16 in 45.1% and 40.2% of patients receiving tofacitinib and vedolizumab, respectively (aOR = 0.82 [0.35-1.91], p = 0.64). Endoscopic improvement (corticosteroid-free clinical remission and endoscopic Mayo score ≤1) (aOR = 0.23[0.08-0.65], p = 0.0032) and histological healing (endoscopic improvement + Nancy histological index ≤1) (13.4% vs 3.2%, aOR = 0.21[0.05-0.91], p = 0.023) were higher at week 16 in patients treated with tofacitinib. No factor was predictive of tofacitinib effectiveness. At least one primary failure to a biologic (OR = 0.46[0.22-0.99], p = 0.049), partial Mayo score >6 (OR = 0.39[0.17-0.90], p = 0.029) and CRP level > 30 mg/L at baseline (OR = 0.08[0.01-0.85], p = 0.036) were associated with vedolizumab failure. CONCLUSION: Tofacitinib and vedolizumab are effective in UC after failure of anti-TNF agents. However, tofacitinib seems more effective, especially in severe disease and primary failure to biologics.

Outcomes of bariatric surgery in patients with inflammatory bowel disease from a French nationwide database.

BACKGROUND: The outcomes of bariatric surgery (BS) in patients with chronic inflammatory bowel disease (IBD) remain rarely described. We aimed to evaluate the 90-day morbidity and mortality rates, and the risk of IBD complications 2 years after BS. METHOD: Patients from the French Programme de Médicalisation des Systèmes d'Information (PMSI) database who underwent a primary BS between 2016 and 2018 were included. We identified patients with a previous diagnosis of IBD. Postoperative 90-day (POD90) morbidity and mortality rates were compared between the two groups. The evolution of IBD was followed 2 years after BS. RESULTS: Between 2016 and 2018, 138 980 patients underwent primary BS, including 587 patients with IBD: 326 (55.5 per cent) with Crohn's disease (CD) and 261 (44.5 per cent) with ulcerative colitis (UC). The preferred surgical technique was sleeve gastrectomy, especially in the IBD group (81.1 per cent), followed by gastric bypass (14.6 per cent). Patients with IBD had more comorbidities (Charlson Comorbidity Index of 1 or more, hypertension, and diabetes; P < 0.001) than those without IBD. The POD90 mortality rate did not differ between the two groups (0.049 per cent in the IBD group versus 0 per cent in the non-IBD group), but more unscheduled rehospitalizations at POD90 were observed in patients with IBD (6.0 per cent versus 3.7 per cent; P = 0.004). Two years after BS, 86 patients (14.6 per cent) in the IBD group had at least one unplanned readmission for the management of their IBD; 15 patients stayed for 3 or more days. After multivariable analysis, patients with CD had an independent elevated risk of IBD-related unplanned readmissions 2 years after BS versus UC (adjusted odds ratio 1.90, 95 per cent c.i. 1.22 to 2.97; P = 0.005). CONCLUSION: In a highly selected cohort of patients with well-controlled IBD, BS did not result in added mortality or morbidity. A point of vigilance must be underlined regarding BS in patients with CD.

Efficacy of ustekinumab, vedolizumab, or a second anti-TNF agent after the failure of a first anti-TNF agent in patients with Crohn's disease: a multicentre retrospective study.

BACKGROUND: No study has performed a face-to-face comparison of biologics after the failure of the first anti-TNF agent in patients with Crohn's disease (CD). The aim of the study was to compare the efficacy of biologics in this setting. METHODS: Patients with CD who were refractory to a first anti-TNF agent, and treated with ustekinumab (UST), vedolizumab (VDZ), or a second anti-TNF drug as a second-line biological agent at 10 French tertiary centres from 2013 to 2019 were retrospectively included in this study. RESULTS: Among the 203 patients included, 90 (44%) received UST, 42 (21%) received VDZ and 71 (35%) received a second anti-TNF agent. The first anti-TNF agent was discontinued due to a primary nonresponse in 42 (21%) patients. At weeks 14-24, the rates of steroid-free remission were similar between the UST, VDZ and second anti-TNF groups (29%, 38% and 44%, respectively, p = 0.15). With a mean follow-up of 118 weeks, drug survival was shorter for patients who received ustekinumab treatment (p = 0.001). In the case of trough level less than 5 µg/ml, patients treated with a second anti-TNF agent had a higher postinduction remission rate (p = 0.002), and drug survival (p = 0.0005). No other relevant factors were associated with treatment efficacy, including trough levels greater than 5 µg/ml. CONCLUSIONS: VDZ, UST and a second anti-TNF agent exhibit similar efficacy in the short term, as second-biological line treatment in patients with CD who are refractory to a first anti-TNF agent, but shorter drug maintenance is observed for patients treated with UST.

Gut microbiota analysis for prediction of clinical relapse in Crohn's disease.

The role of intestinal bacterial microbiota has been described as key in the pathophysiology of Crohn's disease (CD). CD is characterized by frequent relapses after periods of remission which are not entirely understood. In this paper, we investigate whether the heterogeneity in microbiota profiles in CD patients could be a suitable predictor for these relapses. This prospective observational study involved 259 CD patients, in which 41 provided an additional total of 62 consecutive fecal samples, with an average interval of 25 weeks in between each of these samples. Fecal microbiota was analyzed by massive genomic sequencing through 16 S rRNA amplicon sampling. We found that our 259 CD patients could be split into three distinct subgroups of microbiota (G1, G2, G3). From G1 to G3, we noticed a progressive decrease in alpha diversity (p ≤ 0.0001) but no change in the fecal calprotectin (FC) level. Focusing on the 103 consecutive samples from 41 CD patients, we showed that the patients microbiota profiles were remarkably stable over time and associated with increasing symptom severity. Investigating further this microbiota/severity association revealed that the first signs of aggravation are (1) a loss of the main anti-inflammatory Short-Chain Fatty Acids (SCFAs) Roseburia, Eubacterium, Subdoligranumum, Ruminococcus (P < 0.05), (2) an increase in pro-inflammatory pathogens Proteus, Finegoldia (P < 0.05) while (3) an increase of other minor SCFA producers such as Ezakiella, Anaerococcus, Megasphaera, Anaeroglobus, Fenollaria (P < 0.05). Further aggravation of clinical signs is significantly linked to the subsequent loss of these minor SCFAs species and to an increase in other proinflammatory Proteobacteria such as Klebsiella, Pseudomonas, Salmonella, Acinetobacter, Hafnia and proinflammatory Firmicutes such as Staphylococcus, Enterococcus, Streptococcus. (P < 0.05). To our knowledge, this is the first study (1) specifically identifying subgroups of microbiota profiles in CD patients, (2) relating these groups to the evolution of symptoms over time and (3) showing a two-step process in CD symptoms' worsening. This paves the way towards a better understanding of patient-to-patient heterogeneity, as well as providing early warning signals of future aggravation of the symptoms and eventually adapting empirically treatments.

Comparative real-world effectiveness of vedolizumab and ustekinumab for patients with ulcerative colitis: a GETAID multicentre cohort study.

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.