Disease burden of patients with moderate to severe ulcerative colitis: A French multicenter real-life study (THEFAR).

BACKGROUND: Specific studies on the impact of ulcerative colitis (UC) and bowel urgency (BU) on disability and quality of life (QoL) of patients on advanced therapies are missing. METHODS: Clinical and therapeutic management data were collected by Gastroenterologists from adult patients with UC treated with advanced therapies. Patients reported outcomes on QoL were collected using patient-reported questionnaires. RESULTS: Forty-one sites enrolled 293 patients. Median age was 42.0 years, median disease duration was 6.0 years. 38.9 % had active disease (partial Mayo score>1). Median treatment duration was 16.9 months. 166 (57.0 %) patients had BU [median UNRS=2] and 78.3 % had fecal incontinence [median Wexner score=8.0]. Moderate to severe disability (IBD-Disk score≥40) was reported in 37.8 % patients. BU patients had a higher Wexner score [10.0 vs 5.2, p < 0.0001] and moderate to severe disability rate (53.7% vs 16.9 %, p < 0.0001), lower QoL and work productivity than those in BU remission: mean EQ-5D-5 L utility [0.846 vs 0.943, p < 0.0001], VAS for self-rated health [66.2 vs 82.1, p < 0.0001], and overall work impairment [35.7% vs 11.3 %, p < 0.0001]. CONCLUSION: The burden of moderate to severe UC, especially in patients with BU, is high. These findings highlight that BU control remains an unmet medical need in UC patients and underscore the need for new innovative treatments.

Patient preferences for adalimumab in inflammatory bowel disease: a nationwide study from the GETAID.

Background: Several adalimumab preparations are now available for patients with inflammatory bowel disease (IBD). Comparative satisfaction and tolerability are unknown. Objectives: This study investigated IBD patient satisfaction with approved adalimumab biosimilars and their originator. Design: In this cross-sectional study, we included 941 consecutive adalimumab-treated patients with IBD across 45 centres affiliated with the Groupe d'Etude Therapeutique des Affections Inflammatoires du tube Digestif who completed a satisfaction questionnaire comprising four items each rated by a 10-point scale. Methods: The differences in responses were performed using a one-way analysis of variance followed by Tukey's honest significant difference test. Results: The most commonly used drugs at inclusion were Humira® (436/941, 46.3%), Amgevita® (177/941, 18.8%) and Hulio® (105/941, 11.2%). The mean overall satisfaction rate with adalimumab was 8.5 (standard deviation 1.8). Overall satisfaction was significantly higher in patients treated with Humira (8.6 (1.5)), Hulio (8.6 (1.8)) or Amgevita (8.5 (1.4)) (p < 0.05). Satisfaction with the subcutaneous injection form was higher for patients treated with Yuflyma® (9.0 (1.4)), Humira (8.9 (1.3)) and Hulio (8.9 (1.7)) (p < 0.05). A total of 299 patients (31.8%) described injection site reactions. In all, 223 patients (23.7%) reported being previously treated with another adalimumab of which (32/223, 14.3%) discontinued treatment due to side effects. Conclusion: In this real-world setting, patients with IBD had a high level of satisfaction with adalimumab treatment, with some differences in terms of overall satisfaction and satisfaction with the injection device.

Selective inner muscle layer myotomy is associated with lower pain and same clinical efficacy that full-thickness myotomy in patients treated by POEM for achalasia: A multicenter retrospective comparative analysis of 158 patients.

INTRODUCTION: The aim of this study was to compare the impact of the depth of myotomy (selective inner layer myotomy (SIM) vs. full-thickness myotomy (FTM)) on the outcome of patients treated with POEM for achalasia. METHODS: This was a retrospective, observational, conducted in two tertiary centers between October 2018 and September 2022. Patients were divided into two groups: SIM and FTM. The primary endpoint was clinical efficacy at 6 months, while secondary endpoints were postoperative criteria (such as pain, length of hospital stay, complications) and occurrence of gastroesophageal reflux disease (GERD) (esophagitis at 6 months, heartburn, and pH-metry). RESULTS: 158 patients were included in the study (33 in the FTM group and 125 in the SIM group). The success rates at 6 and 12 months were similar in both groups, with 84 % and 70 % in the SIM group versus 90 % and 80 % in the FTM group, respectively (p = 0.57 and p = 0.74). However, more opioid analgesics were consumed in the FTM group compared to the SIM group (41% vs 21 %, p < 0.01). The length of hospitalization was longer in the FTM group than in the SIM group (2.17 ± 2.62 vs 2.94 ± 2.33, p < 0.001). The rate of esophagitis at 6 months was comparable (16 % in the SIM group vs 12 % in the FTM group, p = 0.73). There was no significant difference in terms of heartburn at 6 or 12 months between the SIM and FTM groups (18.5% vs 3.8 %, p = 0.07 and 27% vs 12.5 %, p = 0.35, respectively). CONCLUSION: There was no significant difference in terms of clinical efficacy and GERD occurrence between FTM and SIM. However, full-thickness myotomy was associated with more postoperative pain and a longer length of hospital stay. Therefore, selective internal myotomy should be preferred over full-thickness myotomy.

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

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-TNF failure in UC patients. PATIENTS AND METHODS: In this multicenter 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) (Mayo score partial ≤ 2) was achieved at week 16 in 38.0% and 40.3%, of patients treated with vedolizumab and ustekinumab, respectively (aOR = 1.11 [0.39-3.13], p = 0.85). Rate of SFCR in patients exposed to one line, 2 lines and 3 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 W16 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 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) were observed. While no factor was identified for vedolizumab, primary failure to at least one biologic/small molecule (OR=0.31, 95%CI [0.11-0.82], p=0.018) was significantly associated with 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 to induce endoscopic and histological remission at week 16 after failure of anti-TNFs in UC.

Long-term Outcome of Risankizumab in Crohn's Disease: a Real-world GETAID Study.

BACKGROUND & AIMS: The aim of this study was to assess the long-term effectiveness and safety of risankizumab maintenance treatment in a large real-world cohort of patients with Crohn's Disease (CD). METHODS: From May 2021 to August 2023, all consecutive patients with CD treated with risankizumab in 25 GETAID centers have been retrospectively included. The primary endpoint was steroid-free clinical remission (Harvey Bradshaw Index [HBI] <5) at 52 weeks. RESULTS: Of the 174 patients included, 99%, 93%, and 96% had been previously exposed to anti-TNF, vedolizumab, and ustekinumab, respectively. All patients had received ≥3 biologics, and 108 (62%) had previous intestinal resection. Median follow-up was 13.7 months (interquartile range, 10.0-18.1 months). The rates of steroid-free clinical remission and clinical remission at week 26 were 47% (72/152) and 52% (79/152), and 46% (58/125), and 48% (60/125) at week 52, respectively. Risankizumab persistence rates were 94%, 89%, and 79% at weeks 12, 26, and 52, respectively. At the end of follow-up, 45 (45/174; 26%) patients had discontinued risankizumab (loss of response, 42%; primary failure, 37%; intolerance, 13%). Thirty-six patients (36/174; 20.9%) were hospitalized, and 22 (22/174; 12.6%) required intestinal resection. Fifty-one patients (29%) had an adverse event, including 26 (15%) serious adverse events (CD flare, n = 17). One death (myocardial infarction) and one cancer (papillary thyroid carcinoma) were observed. CONCLUSION: This is the first real-life study to report long-term outcomes in patients with refractory CD treated with risankizumab. One-half of the patients achieved steroid-free clinical remission after 1 year, and the safety profile was consistent with the literature.

Histological healing induced by tofacitinib in ulcerative colitis: A multicentre study.

BACKGROUND: While the efficacy of tofacitinib to induce and maintain clinical and endoscopic remission is well established in ulcerative colitis (UC), little is known about its efficacy to induce histological remission. METHODS: We conducted a retrospective multicentric cohort study. UC patients ≥ 16 years treated by tofacitinib in whom histological activity has been evaluated before and after induction were eligible. The primary endpoint was the histological remission at the end of induction, assessed by the Nancy index and the epithelial neutrophilic infiltrate. RESULTS: A total of 42 patients with UC (93% previously exposed to an anti-TNF and 81% to vedolizumab) were included between July 2018 and April 2022 and were followed for a median duration of 84 weeks [IQR, 35-134]. At the end of induction period (whether prolonged or not), 19% and 24% of patients achieved histological remission, using the Nancy index and the epithelial neutrophilic infiltrate, respectively. Survival without tofacitinib discontinuation was significantly longer in patients without epithelial neutrophilic infiltrate at the end of induction (whether prolonged or not) compared with patients with epithelial neutrophilic infiltrate (p = 0.036). CONCLUSION: Tofacitinib induced histological remission in one fifth to one quarter of patients with UC who have previously failed anti-TNF or/and vedolizumab after induction (whether prolonged or not).

Efficacy and safety of intravenous bevacizumab on severe bleeding associated with hemorrhagic hereditary telangiectasia: A national, randomized multicenter trial.

BACKGROUND: Bevacizumab-a humanized monoclonal antibody-has been widely used to treat patients with hereditary hemorrhagic telangiectasia (HHT), but no randomized trial has yet been conducted. METHODS: This study is a double-blind multicenter randomized phase 2 trial with a 1:1 active-treatment-to-placebo ratio. We included patients over the age of 18 with a confirmed diagnosis and the need for at least four red blood cell (RBC) units transfused in the 3 months before study enrollment. Bevacizumab was administered at a dose of 5 mg/kg every 14 days with a total of six injections. The primary efficacy criterion was a decrease of at least 50% in the cumulative number of RBC units transfused in a 3-month period before and after treatment. RESULTS: A total of 24 patients (12 in each group) were included and randomized at 4 different centers. In intention-to-treat analysis, 63.6% of patients (7/11) in the bevacizumab group versus 33.3% of patients (4/12) in the placebo group decreased the number of blood transfusions by at least 50% (p = 0.22). Hemoglobin levels significantly improved at 6 months in the bevacizumab versus placebo group (p = 0.02). The pharmacokinetics study revealed that patients with high exposure to bevacizumab had a significant decrease in RBC transfusions (p = 0.03). Fifty-nine adverse events were observed, 34 in the placebo arm versus 25 in the bevacizumab arm. CONCLUSION: Though the present trial was underpowered, patients with HHT receiving bevacizumab required numerically fewer red blood cell transfusions than those receiving placebo, particularly those with high exposure.

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.

Comparative Evaluation of Four Commercially Available Immunoassays for Therapeutic Drug Monitoring of Infliximab and Adalimumab.

Therapeutic drug monitoring (TDM) of anti-TNF-α is an important tool in clinical practice for inflammatory diseases. In this study, we have evaluated the performance of several assays for drug and antidrug antibodies (ADA) measurement in the serum. 50 sera from patients treated with infliximab (IFX) and 49 sera from patients treated with adalimumab (ADAL) were monitored with four immunoassays. We have compared Promonitor, i-Track10®, and ez-track1 assays to our gold standard Lisa Tracker® ELISA using Cohen's kappa, Passing-Bablok, and Bland-Altman analysis. The qualitative analysis evaluated by Cohen's kappa values found for IFX measurements an "almost perfect" concordance for Promonitor, "moderate" for i-Track10® and "substantial" for ez-Track1. For ADAL, kappa values were "moderate" for all tested methods. For anti-IFX, kappa values were "almost perfect" for Promonitor, "fair" for i-Track10®, and "substantial" for ez-Track1. For anti-ADAL, kappa values were "almost perfect" for all three assays. For quantitative analysis of drug measurements, Pearson's r values were all above 0.9 and Lin's concordance coefficients of all immunoassays were around 0.80. Performances of the four evaluated immunoassays were acceptable for TDM based on our laboratory experience. Nevertheless, concordance between the four methods for IFX measurement was not perfect and we recommend the use of the same assay for the follow-up of a given patient. The performances of the four immunoassays evaluated were similar and are acceptable for TDM based on our laboratory experience.

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 infection in elderly patients with inflammatory bowel disease under biologics: A prospective, multicenter, observational, one-year follow-up comparative study.

OBJECTIVES: The emergence of biologics has improved the course of inflammatory bowel diseases (IBD) in the elderly population despite a potential higher risk of infections. We conducted a one-year, prospective, multicenter, observational study to determine the frequency of occurrence of at least one infectious event in elderly IBD patients under anti-TNF therapy compared with that in elderly patients under vedolizumab or ustekinumab therapies. METHODS: All IBD patients over 65 years exposed to anti-TNF, vedolizumab or ustekinumab therapies were included. The primary endpoint was the prevalence of at least one infection during the whole one year follow-up. RESULTS: Among the 207 consecutive elderly IBD patients prospectively enrolled, 113 were treated with anti-TNF and 94 with vedolizumab (n=63) or ustekinumab (n=31) (median age 71 years, 112 Crohn's disease). The Charlson index was similar between patients under anti-TNF and those under vedolizumab or ustekinumab as well as the proportion of patients under combination therapy and under concomitant steroid therapy did not differ between both both groups. The prevalence of infections was similar in patients under anti-TNF and in those under vedolizumab or ustekinumab (29% versus 28%, respectively; p=0.81). There was no difference in terms of type and severity of infection and of infection-related hospitalization rate. In multivariate regression analysis, only the Charlson comorbidity index (≥ 1) was identified as a significant and independent risk factor of infection (p=0.03). CONCLUSION: Around 30 % of elderly patients with IBD under biologics experienced at least one infection during the one-year study follow-up period. The risk of occurrence of infection does not differ between anti-TNF and vedolizumab or ustekinumab therapies, and only the associated comorbidity was linked with the risk of infection.

Effectiveness of golimumab intensification in ulcerative colitis: A multicentric prospective study.

INTRODUCTION: Loss of response to golimumab occurs in nearly 40% of patients with ulcerative colitis (UC). Unlike others anti-TNF, no study has reported a correlation between serum golimumab level and response to drug intensification. The objective of this study was to evaluate the effectiveness and safety of golimumab intensification and to identify the best threshold of serum golimumab before drug intensification predictive of response. PATIENTS AND METHODS: We included all consecutive patients with active UC with loss of response to golimumab in a prospective multicentric cohort study. Patients with loss of response at 50 mg q4 weeks (W) and 100 mg q4W underwent therapeutic intensification at 100 mg q4W and 100 mg q2W, respectively. Effectiveness and safety were assessed between Weeks 2 and 4 (visit 2) and between Weeks 4 and 8 (visit 3) after intensification. Serum level and anti-golimumab antibodies were evaluated at each medical visit (Lisa Tracker, Theradiag France). RESULTS: A total of 47 UC patients (Female, 50%; median age, 39 years (IQR, 27-52)) treated with golimumab for a median of 20.4 weeks (IQR, 10.7-38.3) were included. The median partial Mayo score was 6 (IQR, 5-7), and the median endoscopic Mayo score was 3 (IQR, 2-3). The median golimumab serum level before intensification was 2.23 µg/mL (IQR, 1.02-3.96) and only one patient (2.1%) had anti-drug antibodies. At Visit 2 (Week 2-4), 40% patients experienced clinical response, 10% clinical remission, 33% endoscopic response and 23% endoscopic remission. At Visit 3 (Week 4-8), 44% of patients had clinical response, 22% of patients had clinical remission, 45% of patients had endoscopic response, and 41% of patients had endoscopic remission. The median golimumab levels before intensification do not differ between responders and non-responders (2.13 µg/ml (0.76-2.76) and 3.37 µg/ml (IQR, 1.08-4.67), respectively; p = 0.14) assessed at Visit 3. Golimumab intensification to 100 mg q4W (vs q2W) (OR 1.98, 95% CI [1.06-3.70]; p = 0.032) was significantly associated with clinical remission at Visit 3. Serum drug level at baseline or the presence of antidrug antibodies were not associated with clinical or endoscopic remission/response. Two serious adverse events (one infection and one UC flare) were reported during the 24-week follow-up. CONCLUSION: In this prospective multicentric study, half of patients recaptured response following golimumab intensification in UC. Therapeutic drug monitoring did not predict response after optimisation of golimumab.

Adalimumab in Biologic-naïve Patients With Crohn's Disease After Resolution of an Intra-abdominal Abscess: A Prospective Study From the GETAID.

BACKGROUND & AIMS: The management of intra-abdominal abscesses complicating Crohn's disease (CD) is challenging, and surgery with delayed intestinal resection is often recommended. The aims of this study were to estimate the success rate of adalimumab (ADA) in patients with CD with an intra-abdominal abscess resolved without surgery, and to identify predictive factors for success. METHODS: A multicenter, prospective study was conducted in biologic-naïve patients with CD with resolved intra-abdominal abscess treated with ADA with a 2-year follow-up. The primary endpoint was ADA failure at week (W) 24 defined as a need for steroids after W12, intestinal resection, abscess recurrence, and clinical relapse. Secondary post-hoc endpoint was the long-term success defined as the survival without abscess relapse or intestinal resection at W104. The factors associated with ADA failure at W24 and W104 were identified using a logistic and a Cox regression, respectively. RESULTS: From April 2013 to December 2017, 190 patients from 27 GETAID centers were screened, and 117 were included in the analysis. Fifty-eight patients (50%) were male, and the median age at baseline was 28 years. At W24, 87 patients (74%; 95% confidence interval [CI], 65.5%-82.0%; n = 117) achieved ADA success. Among the 30 patients with ADA failure, 15 underwent surgery. At W104, the survival rate without abscess recurrence or surgery was 72.9% (95% CI, 62.1%-79.8%; n = 109). Abscess drainage was significantly associated with ADA failure at W24 (odds ratio, 4.18; 95% CI, 1.06-16.5; P =0 .043). Disease duration (hazard ratio [HR], 1.32; 95% CI, 1.09-1.59; P = .008), abscess drainage (HR, 5.59; 95% CI, 2.21-14.15; P = .001), and inflammatory changes in mesenteric fat (HR, 0.4; 95% CI, 0.17-0.94; P = .046) were significantly associated with ADA failure at W104. CONCLUSION: Provided that the abscess was carefully managed before initiating medical treatment, this study showed the high efficacy of ADA in the short and long term in biologic-naïve patients with CD complicated by an intra-abdominal abscess. CLINICALTRIALS: gov, Number: NCT02856763.

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.

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.

Prevention of post-operative recurrence of Crohn's disease among patients with prior anti-TNFα failure: A retrospective multicenter study.

BACKGROUND: Anti-TNFα are recommended for preventing Crohn's disease (CD) postoperative recurrence (POR) in patients with risk factors. However, few data exploring anti-TNFα efficacy in patients with preoperative anti-TNFα failure are available so far. AIMS: The aim of the present study was to compare the efficacy of anti-TNFα with other biologics and immunosuppressants to prevent POR in this setting. METHODS: Consecutive CD patients who underwent bowel resection between January 2010 and December 2019 after failure of at least one anti-TNFα were retrospectively included among three tertiary centers if they started a postoperative medical prophylaxis within the three months after index surgery. The main outcome was to compare rates of objective recurrence (endoscopic or radiological recurrence in absence of colonoscopy) between patients treated with an anti-TNFα agent or another treatment as prevention of POR. RESULTS: Among the 119 patients included, 71 patients received an anti-TNFα (26 infliximab, 45 adalimumab) and 48 another treatment (18 ustekinumab, 7 vedolizumab, 20 azathioprine and 3 methotrexate) to prevent POR. Rates of objective recurrence at two years were 23.9% in patients treated with anti-TNFα and 44.9% in the others (p = 0.011). CONCLUSION: Anti-TNFα remained an effective option to prevent POR for patients operated upon with previous anti-TNFα failure.

Effectiveness and safety of risankizumab induction therapy for 100 patients with Crohn's disease: A GETAID multicentre cohort study.

BACKGROUND: Phase III trials have demonstrated the efficacy of risankizumab in moderate-to-severe Crohn's disease (CD), but no real-world data are currently available. We aimed to assess the short-term effectiveness and safety of risankizumab in patients with CD. METHODS: From May 2021 to May 2022, all patients with refractory luminal CD treated with risankizumab in 22 French GETAID centres were retrospectively included. The primary endpoint was steroid-free clinical remission at week 12 (Harvey-Bradshaw [HB] score <5). Secondary endpoints included clinical response (≥3-point decrease of HB score and/or (HB) score <5), biochemical remission (CRP ≤ 5 mg/L), need for CD-related surgery and adverse events. RESULTS: Among the 100 patients included, all have been previously exposed to anti-TNF agents, 94 to vedolizumab, 98 to ustekinumab (all exposed to at least three biologics) and 61 had a previous intestinal resection. All but three (97%) received a 600 mg risankizumab intravenous induction at weeks 0-4-8. At week 12, steroid-free clinical remission was observed in 45.8% of patients, clinical remission in 58% and clinical response in 78.5%. In subgroup analysis restricted to patients with objective signs of inflammation at baseline (n = 79), steroid-free clinical remission at week 12 was observed in 39.2% of patients. Biochemical remission was observed in 50% of patients. Six patients discontinued risankizumab before the week 12 visit due to lack of efficacy. CD-related hospitalisation was needed in six patients, and three underwent intestinal resection. In multivariable analysis, only a history of ustekinumab loss of response (vs primary failure) (odds ratio (OR), 2.80; 95% CI: 1.07-7.82; p = 0.041) was significantly associated with clinical remission at week 12. Twenty adverse events (AE) occurred in 20 patients including 7 serious AE corresponding to 6 CD exacerbation and one severe hypertension. CONCLUSION: In a cohort of highly refractory patients with luminal CD and multiple prior drug failures including ustekinumab, risankizumab induction provided a clinical response in about 3 out of 4 patients and steroid-free clinical remission in about half of patients.

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.

A rapid and standardized workflow for functional assessment of bacterial biosensors in fecal samples.

Gut metabolites are pivotal mediators of host-microbiome interactions and provide an important window on human physiology and disease. However, current methods to monitor gut metabolites rely on heavy and expensive technologies such as liquid chromatography-mass spectrometry (LC-MS). In that context, robust, fast, field-deployable, and cost-effective strategies for monitoring fecal metabolites would support large-scale functional studies and routine monitoring of metabolites biomarkers associated with pathological conditions. Living cells are an attractive option to engineer biosensors due to their ability to detect and process many environmental signals and their self-replicating nature. Here we optimized a workflow for feces processing that supports metabolite detection using bacterial biosensors. We show that simple centrifugation and filtration steps remove host microbes and support reproducible preparation of a physiological-derived media retaining important characteristics of human feces, such as matrix effects and endogenous metabolites. We measure the performance of bacterial biosensors for benzoate, lactate, anhydrotetracycline, and bile acids, and find that they are highly sensitive to fecal matrices. However, encapsulating the bacteria in hydrogel helps reduce this inhibitory effect. Sensitivity to matrix effects is biosensor-dependent but also varies between individuals, highlighting the need for case-by-case optimization for biosensors' operation in feces. Finally, by detecting endogenous bile acids, we demonstrate that bacterial biosensors could be used for future metabolite monitoring in feces. This work lays the foundation for the optimization and use of bacterial biosensors for fecal metabolites monitoring. In the future, our method could also allow rapid pre-prototyping of engineered bacteria designed to operate in the gut, with applications to in situ diagnostics and therapeutics.