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Background Both vedolizumab and ustekinumab can be considered for the treatment of ulcerative colitis [UC], but head-to-head trials are lacking. Aim We aimed to compare the effectiveness of vedolizumab and ustekinumab after anti-tumour necrosis factor [anti-TNF] failure in UC patients. Patients and Methods In this multicentre study, we included consecutive adult patients with UC, with partial Mayo score >2 and prior anti-TNF exposure, treated with vedolizumab or ustekinumab between January 2019 and August 2022. Comparisons were performed using propensity score analyses [inverse probability of treatment weighting]. Results Among a total of 293 patients included, 151 and 142 received vedolizumab and ustekinumab, respectively. After propensity score analysis, steroid-free clinical remission [SFCR] [partial Mayo score ≤2] was achieved at week 16 in 38.0% and 40.3% of patients treated with vedolizumab and ustekinumab, respectively (adjusted odds ratio [aOR] = 1.11, 95% confidence interval [0.39–3.13], p  = 0.85). Rates of SFCR in patients exposed to one, two, and three lines of biologics/small molecules among patients treated with vedolizumab and ustekinumab were respectively 53.3% vs 62.1% [ p  = 0.52], 44.4% vs 33.8% [ p  = 0.52], and 2.6% vs 19.1% [ p  = 0.027]. Endoscopic remission [SFCR and endoscopic Mayo score ≤1] and histological remission [SFCR, endoscopic remission, and Nancy histological index ≤1] at week 16 were achieved in respectively 5.3% vs 17.5% (aOR = 3.77 [1.25–11.36], p  = 0.018) and 2.1% vs 11.1% (aOR = 5.85 [1.47–23.30], p  = 0.012) in the vedolizumab and ustekinumab groups. No difference regarding the risk of drug discontinuation between the two groups (aHR = 1.03 [0.51–2.08], p  = 0.92) was observed. While no factor was identified for vedolizumab, primary failure to at least one biologic/small molecule (OR = 0.31 [0.11–0.82], p  = 0.018) was significantly associated with a decreased rate of SFCR among patients treated with ustekinumab. Conclusion While no difference in terms of short-term clinical remission was observed, ustekinumab appears to be more effective than vedolizumab in inducing endoscopic and histological remission at week 16 after failure of anti-TNFs in UC. [ABSTRACT FROM AUTHOR]

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. To identify the factors associated with obese and overweight patients with IBD, including IBD-related disability. 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). 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). 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. [ABSTRACT FROM AUTHOR]

There are currently no comparative data on the efficacy and safety of vedolizumab and ustekinumab in ulcerative colitis (UC) after anti-TNF therapy fails. 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. 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. 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 FROM AUTHOR]

Objective The association of IgA vasculitis (IgAV) and IBD is rarely described, mainly during anti-TNF-α 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-α 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-α were discontinued in 15/28 (54%). No IgAV relapse occurred when TNF-α blockers were stopped, vs 23% in patients pursuing it. Conversely, five (33%) had IBD flare or complication after anti-TNF-α cessation vs one (8%) in those continuing biologics. Anti-TNF-α were resumed in six (40%), with subsequent IgAV relapse in four (67%). Conclusions This large cohort suggests that TNF-α blockers may promote the onset of IgAV in IBD. Discontinuation of anti-TNF-α was associated with vasculitis remission but increased risk of IBD relapses, whereas continuation of anti-TNF-α was associated with IBD remission but vasculitis relapse. [ABSTRACT FROM AUTHOR]

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Summary: Background: Phase III trials have demonstrated the efficacy and safety of ustekinumab in ulcerative colitis (UC), but few real‐life long‐term data are currently available. Aims: To assess the real‐world effectiveness and safety of ustekinumab in patients with UC. Methods: From January to September 2019, all consecutive patients with active UC treated with ustekinumab in a GETAID centre were included. Patients were evaluated at week 52. Remission was defined as a partial Mayo Clinic score ≤2. Results: We included 103 patients with UC (62 men; mean age: 41.2 ± 16.2 years; 52% pancolitis E3) with an insufficient response to immunosuppressants, anti‐TNFs and/or vedolizumab. At week 52, 45 (44%) patients had discontinued ustekinumab mainly due to lack of effectiveness (n = 41). The cumulative probabilities of ustekinumab persistence were 96.1%, 81.6%, 71.7% and 58.4% after 3, 6, 9 and 12 months respectively. The overall steroid‐free clinical remission rate at week 52 was 32% of whom 71% had subscores of null for rectal bleeding and stool frequency. Ten patients underwent colectomy within a median of 6.7 [4.3‐10.6] months. Adverse effects were observed in 15 (16.9%) patients; 4 (4.5%) were severe, including one patient who died from a myocardial infarction. Conclusion: After 52 weeks, over one‐half of patients with refractory UC were still treated by ustekinumab and one‐third were in steroid‐free clinical remission. [ABSTRACT FROM AUTHOR]

Summary: Background: Up to 25% of patients with ulcerative colitis (UC) will require hospitalization for severe flare. In patients hospitalised for severe flare, who previously experienced multiple drug failures, including steroids and anti‐TNF agents, new quick‐acting medical options are needed. Tofacitinib is effective in refractory UC and has a rapid onset of action. Aim: To evaluate effectiveness and safety of tofacitinib as rescue therapy in patients hospitalised for UC flare. Methods: We conducted an observational and multicentre study with both retrospective and prospective collections in 14 GETAID centres. The primary objective was to assess the survival without colectomy following tofacitinib initiation in patients hospitalised for a UC flare. We determined rates of clinical response, clinical remission, and steroid‐free clinical remission at week 6 and week 14 and safety. Results: Fifty‐five patients were included (49 with prior infliximab failure and 19 previously exposed to ciclosporin). With a median follow‐up of 6.5 months (interquartile range [IQR] [3‐12.3]), rate of colectomy‐free survival was estimated at 78.9% (95 CI [68.5‐90.9]) and 73.6% (95 CI [61.9‐87.3]) at 3 and 6 months, respectively. Rates of clinical response, clinical remission and steroid‐free clinical remission were 60%, 45.5% and 37.5% at week 6 and 41.8%, 34.5% and 32.7% at week 14. Regarding safety, no death was observed, three patients withdrew tofacitinib due to adverse events. Two herpes zoster infections occurred in patients aged over 60 years old. No venous thrombotic or major adverse cardiovascular events occurred. Conclusion: Tofacitinib appears as a promising option in patients hospitalised with a UC flare but needs further validation in controlled trials. [ABSTRACT FROM AUTHOR]

Summary: Background: The 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. Aims: To identify the predictive factors of disability in a large population of patients with IBD. Patients and methods: We 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. Results: Among 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. Conclusion: Determinants 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. [ABSTRACT FROM AUTHOR]

Patients' experience with healthcare professionals could influence their clinical outcomes. To assess inflammatory bowel disease (IBD) patients' experience with their disease, their treatment and their relationship with their physician. 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. 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. 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. [ABSTRACT FROM AUTHOR]

Summary: Background: Phase 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. Aim: To assess short‐term effectiveness and safety of ustekinumab in patients with UC. Methods: From 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. Results: Among 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. Conclusion: In 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. [ABSTRACT FROM AUTHOR]

Background Whether vedolizumab may be effective as a treatment for primary sclerosing cholangitis [PSC] in patients with inflammatory bowel disease [IBD] remains controversial. Methods We performed a retrospective observational study of consecutive patients with IBD and PSC, treated with vedolizumab for at least 30 weeks in 22 centres of GETAID from January 2015 to June 2016. The outcomes included a decrease in the serum alkaline phosphatase [ALP] concentration of at least 50% from baseline to Week 30 or 54, a change in any serum liver enzymes concentrations, and an assessment of the efficacy and safety of vedolizumab in IBD. Results Among 75 patients with active IBD and PSC treated with vedolizumab, 21 patients discontinued vedolizumab before Week 30 [due to lack of efficacy in 19 and malignancy in two patients]. In the remaining 54 patients, a decrease in the serum ALP concentration of at least 50% from baseline to Weeks 30 and 54 was observed in four [7%] and four [11%] patients, respectively. No significant change was observed in serum liver enzyme concentrations at week 30 or 54. After a median follow-up period of 19.4 [14.0–29.9] months, nine cases of digestive neoplasia [colorectal neoplasia in seven and cholangiocarcinoma in two] were reported. Conclusions In patients with IBD and PSC, vedolizumab did not improve serum liver enzyme concentrations at week 30 or 54. Nine cases of digestive cancer occurred during the follow-up period, confirming the need for a tight surveillance programme in this population. [ABSTRACT FROM AUTHOR]

Abstract Background Data about the outcomes after adalimumab dose de-escalation in inflammatory bowel disease (IBD) are scarce. Objectives To assess the outcomes after adalimumab dose de-escalation, and to identify potential factors associated with failure. Methods Retrospective, observational study including all IBD patients who had undergone adalimumab dose de-escalation to 40 mg every three weeks across seven GETAID centers, between June 2011 and September 2017. Failure of adalimumab dose de-escalation was defined as the need for treatment re-escalation, discontinuation of adalimumab, or clinical, biochemical and/or morphologic disease relapse. Results Fifty-six patients were identified (n = 46 Crohn's disease, n = 10 ulcerative colitis). Median (IQR) duration of follow-up after adalimumab dose de-escalation was 15.9 (7.9–30.6) months. Adalimumab dose de-escalation was a failure in 21/56 (37.5%) patients and successful in 35/56 (62.5%) patients. Median (IQR) time until failure was 8.9 (4.6–15.6) months. At multivariate analysis, inactive disease at magnetic resonance imaging and/or endoscopy in the year before adalimumab dose de-escalation decreased the risk of failure with a factor five (P = 0.02). Conclusions Adalimumab dose de-escalation to 40 mg every three weeks is possible in almost two thirds of IBD patients. Objective morphologic signs of active disease should be ruled out before considering a de-escalation strategy with adalimumab. [ABSTRACT FROM AUTHOR]

Summary: Background: Genital fistulas represent a devastating complication of Crohn's disease. Only studies with small sample sizes have evaluated the efficacy of anti‐TNF therapy for this complication. Aims: To assess the efficacy of anti‐TNF therapy for genital fistulas complicating Crohn's disease and to identify predictive factors associated with clinical response at 1 year. Methods: Consecutive patients treated with anti‐TNF therapy for genital fistulas complicating Crohn's disease from 1999 to 2016 in 19 French centres from the Groupe d'Etude Thérapeutique des Affections Inflammatoires du tube Digestif were included in a retrospective cohort study. Outcome was clinical fistula closure at 1 year. Results: Among the 204 women with genital fistulas who received anti‐TNF therapy, 131 were analysed. The first anti‐TNF given was infliximab (79%), adalimumab (20%), or certolizumab (1%). At start of anti‐TNF therapy, 56% of patients had seton drainage and 53% had concomitant immunosuppressive treatment. A complementary surgery was performed during the first year in 10 patients (8%). At 1 year, 37% of patients had complete clinical fistula closure, 22% had a partial response, and 41% had no response. Among patients without complementary surgery, 34% (41/121) had complete clinical fistula closure. Only complementary surgery was associated with better response on multivariate analysis (adjusted relative risk: 2.02, 95% CI: 1.25‐3.26, P = 0.0043). Conclusions: In the anti‐TNF era, approximately one‐third of patients with genital fistula in Crohn's disease had complete fistula closure at 1 year. Collaboration between surgeons and gastroenterologists appears to be very important to improve the rate of fistula closure. [ABSTRACT FROM AUTHOR]

Background and Aims: Using sigmoidoscopy as the gold standard, we assessed the accuracy, and the responsiveness to change, of diffusion-weighted magnetic resonance colonography in ulcerative colitis, using the Nancy score. Methods: A total of 29 ulcerative colitis patients, having undergone at least two diffusion-weighted magnetic resonance colonographies, were included. Disease activity was evaluated using the Mayo endoscopic subscore and the Nancy score. We determined the accuracy of the Nancy score in the diagnosis of mucosal healing. We also assessed its responsiveness to change in 17 patients with a Mayo endoscopic subscore of 2 or 3 at treatment initiation. Results: A total Nancy score < 7 had a sensitivity of 0.75 and a specificity of 0.67 (area under the curve: 0.72; 95% confidence interval: [0.56–0.88]; p = 0.0063) in the diagnosis of mucosal healing. The total Nancy score was sensitive to change in ulcerative colitis [Guyatt’s responsiveness index: 1.8; standardised effect size ratio: 1.36]. The Nancy score was reliable [intra-class correlation coefficient: 0.63; p = 0.01]. The mean Mayo endoscopic subscore and the mean Nancy score both fell significantly in patients who achieved mucosal healing (mean ± standard deviation [SD] Mayo endoscopic subscore: 2.4 ± 0.55 at baseline and 0.6 ± 0.55 at reassessment, p = 0.02; mean Nancy score: 18.2 ± 9.1 at baseline and 3 ± 1.6 at reassessment, p = 0.006). No significant changes in Nancy score were observed in active patients at reassessment. Conclusions: The Nancy score is a highly responsive, reliable tool for assessing treatment response in patients with ulcerative colitis. The Nancy score accurately detects mucosal healing. [ABSTRACT FROM AUTHOR]

Background Although the rs2476601 polymorphism of PTPN22 has been reported to be a susceptibility gene for Crohn's disease (CD), results from different studies vary and remain inconclusive. Also, no association has been found between rs2476601 and the risk of ulcerative colitis (UC). The aim of this meta-analysis was to investigate the association between this PTPN22 polymorphism (rs2476601) and the risk of inflammatory bowel disease, UC and CD. Methods We performed a meta-analysis by identifying relevant candidate gene-based studies from EMBASE and MEDLINE. Odds ratios (OR) and 95% confidence intervals (CI) were calculated to estimate the strength of associations between rs2476601 and inflammatory bowel diseases, using a fi xed effect or random effect model. Publication bias was also assessed. Results By pooling 14 different studies, 13,356 controls, 8182 patients with CD, and 8656 with UC were included. We found that the T allele of PTPN22 was not significantly associated with a higher risk of developing UC (OR 1.06, 95%CI 0.98-1.14) but was associated with a decreased risk of developing CD (OR 1.28, 95%CI 1.17-1.40). The T allele in rs2476601 lowered the risk of CD by 22%. Conclusion Th is study shows that PTPN22 (rs2476601) is significantly associated with the risk of developing CD, but has no association with UC. Th is suggests that these diseases have different pathways involved in their pathophysiology. [ABSTRACT FROM AUTHOR]

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. 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. 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]. 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. [ABSTRACT FROM AUTHOR]