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.

Identifying, Understanding, and Managing Fecal Urgency in Inflammatory Bowel Diseases.

BACKGROUND & AIMS: Fecal urgency, which is defined by the sudden need to rush to the bathroom to empty one's bowel, is one of the common and distressing symptoms experienced by patients with inflammatory bowel disease. METHODS: We performed a narrative review to investigate the definition, pathophysiology, and therapeutic management of fecal urgency. RESULTS: Definitions of fecal urgency in inflammatory bowel disease, but also in irritable bowel syndrome, oncology, nononcologic surgery, obstetrics and gynecology, and in proctology, are empirical and heterogenous, lacking standardization. In the majority of these studies, nonvalidated questionnaires were used. When nonpharmacologic measures (dietary regimen, cognitive behavioral program) fail, medications such as loperamide, tricyclic antidepressants, or biofeedback therapy may become necessary. Medical management of fecal urgency may be challenging, in part because only limited data are available regarding the treatment of this symptom in randomized clinical trials of biologics in patients with inflammatory bowel disease. CONCLUSIONS: There is an urgent need for a systematic approach to assessment of fecal urgency in inflammatory bowel disease. It is time to consider fecal urgency as an outcome in clinical trials to remedy this disabling symptom.

Preoperative Magnetic Resonance Enterography to Predict Pathological Specimen Length in Crohn's Disease.

BACKGROUND: The European Crohn's and Colitis Organization guidelines have highlighted the importance of the preoperative evaluation of the affected segment length in patients with ileocolic Crohn's disease to determine the best surgical approach. OBJECTIVE: This study aimed to evaluate the accuracy of preoperative magnetic resonance enterography in assessing the length of the affected segment in patients with ileocolic Crohn's disease. DESIGN: This observational study was conducted with a prospectively maintained database and retrospective analysis. SETTINGS: This study was conducted in a tertiary center. PATIENTS: This study included consecutive patients undergoing ileocolic resection for Crohn's disease between August 2014 and June 2020. All patients underwent a preoperative magnetic resonance enterography. MAIN OUTCOME MEASURES: The correlation between the length measured on magnetic resonance enterography and pathological examination was evaluated. RESULTS: A total of 96 patients were included. The median time between magnetic resonance enterography and surgery was 65.5 (3-331) days. The length of the affected segment on magnetic resonance enterography was correlated with the length assessed on pathological evaluation ( R = 0.48, p < 0.001). No correlation was found between the 2 measurements when imaging was performed >6 months before surgery ( R = 0.14, p = 0.62). The presence of an abscess underestimated the length affected by Crohn's disease on imaging compared to pathology, whereas the presence of a fistula was associated with magnetic resonance enterography overestimation of the length of the affected segment. LIMITATIONS: Limitations included single-center study and retrospective analysis. CONCLUSION: In Crohn's disease, preoperative magnetic resonance enterography is a highly reliable tool for predicting the length of the affected segment compared to pathology examination in the absence of an abscess or fistula. See Video Abstract at http://links.lww.com/DCR/C26 . ENTEROGRAFA POR RESONANCIA MAGNTICA PREOPERATORIA PARA PREDECIR LA LONGITUD DE MUESTRAS PATOLGICAS EN LA ENFERMEDAD DE CROHN: ANTECEDENTES:Las guías de la Organización Europea de Crohn y Colitis han resaltado la importancia de la evaluación preoperatoria de la longitud del segmento afectado para determinar el mejor abordaje quirúrgico.OBJETIVO:Evaluamos la precisión de la enterografía por resonancia magnética preoperatoria para evaluar la longitud del segmento afectado en pacientes con enfermedad de Crohn ileocólica.DISEÑO:Realizamos un estudio observacional con una base de datos mantenida prospectivamente y un análisis retrospectivo.CONFIGURACIÓN:Este estudio se realizó en un centro terciario.PACIENTES:Se incluyeron pacientes consecutivos sometidos a resección ileocólica por enfermedad de Crohn entre Agosto de 2014 y Junio de 2020. A todos los pacientes se les realizó una enterografía por resonancia magnética preoperatoria.PRINCIPALES MEDIDAS DE RESULTADO:Se evaluó la correlación entre la longitud medida en la enterografía por resonancia magnética y el examen patológico.RESULTADOS:Se incluyeron un total de 96 pacientes. El tiempo mediano entre la enterografía por resonancia magnética y la cirugía fue de 65,5 (3-331) días. La longitud del segmento afectado en la enterografía por resonancia magnética se correlacionó con la longitud evaluada en la evaluación patológica ( R = 0,48, p < 0,001). No hubo correlación entre las 2 mediciones cuando las imágenes se realizaron más de 6 meses antes de la cirugía ( R = 0,14, p = 0,62). La presencia de un absceso subestimó la longitud afectada por la enfermedad de Crohn en las imágenes en comparación con la patología, mientras que la presencia de una fístula se asoció con una sobrestimación de la longitud del segmento afectado por enterografía por resonancia magnética.LIMITACIONES:Las limitaciones incluyeron un estudio de un solo centro y un análisis retrospectivo.CONCLUSIÓNES:En la enfermedad de Crohn, la enterografía por resonancia magnética preoperatoria es una herramienta altamente confiable para predecir la longitud del segmento afectado en comparación con el examen de patología, en ausencia de absceso o fístula. Consulte el Video Resumen en http://links.lww.com/DCR/C26 . (Traducción-Dr. Yesenia Rojas-Khalil ).

International Consensus on Definition of Mild-to-Moderate Ulcerative Colitis Disease Activity in Adult Patients.

Background and Objectives: At present, there is no consensus definition of mild-to-moderate disease activity in patients with ulcerative colitis. The objective of the present study was to establish a reliable definition of mild-to-moderate disease activity in adult patients with ulcerative colitis. Materials and Methods: Twelve physicians from around the world participated in a virtual consensus meeting on 26 September 2022. All the physicians had expertise in the diagnosis and treatment of inflammatory bowel disease. After a systematic review of the literature and expert opinion, a modified version of the RAND/University of California, Los Angeles appropriateness method was applied. A total of 49 statements were identified and then anonymously rated (on a 9-point scale) as being appropriate (scores of 7 to 9), uncertain (4 to 6) or inappropriate (1 to 3). The survey results were reviewed and amended before a second round of voting. Results: Symptom and endoscopic-based measurements are of prime importance for assessing mild-to-moderate ulcerative colitis activity in clinical trials. The experts considered that clinical activity should be assessed in terms of stool frequency, rectal bleeding and fecal urgency, whereas endoscopic activity should be evaluated with regard to the vascular pattern, bleeding, erosions and ulcers. Fecal calprotectin was considered to be a suitable disease activity marker in mild-to-moderate ulcerative colitis. Lastly, mild-to-moderate ulcerative colitis should not have more than a small impact on the patient's daily activities. Conclusions: The present recommendations constitute a standardized framework for defining mild-to-moderate disease activity in clinical trials in the field of ulcerative colitis.

Sugars and Gastrointestinal Health.

Sugar overconsumption is linked to a rise in the incidence of noncommunicable diseases such as diabetes, cardiovascular diseases, and cancer. This increased incidence is becoming a real public health problem that is more severe than infectious diseases, contributing to 35 million deaths annually. Excessive intake of free sugars can cause many of the same health problems as excessive alcohol consumption. Many recent international recommendations have expressed concerns about sugar consumption in Westernized societies, as current consumption levels represent quantities with no precedent during hominin evolution. In both adults and children, the World Health Organization strongly recommends reducing free sugar intake to <10% of total energy intake and suggests a further reduction to below 5%. Most studies have focused on the deleterious effects of Western dietary patterns on global health and the intestine. Whereas excessive dietary fat consumption is well studied, the specific impact of sugar is poorly described, while refined sugars represent up to 40% of caloric intake within industrialized countries. However, high sugar intake is associated with multiple tissue and organ dysfunctions. Both hyperglycemia and excessive sugar intake disrupt the intestinal barrier, thus increasing gut permeability and causing profound gut microbiota dysbiosis, which results in a disturbance in mucosal immunity that enhances infection susceptibility. This review aims to highlight the roles of different types of dietary carbohydrates and the consequences of their excessive intake for intestinal homeostasis.

IOIBD Recommendations for Clinical Trials in Ulcerative Proctitis: The PROCTRIAL Consensus.

BACKGROUND & AIMS: Clinical trials evaluating biologics and small molecules in patients with ulcerative colitis are predominantly excluding ulcerative proctitis. The objective of the Definition and endpoints for ulcerative PROCtitis in clinical TRIALs initiative was to develop consensus statements for definitions, inclusion criteria, and endpoints for the evaluation of ulcerative proctitis in adults. METHODS: Thirty-five international experts held a consensus meeting to define ulcerative proctitis, and the endpoints to use in clinical trials. Based on a systematic review of the literature, statements were generated, discussed, and approved by the working group participants using a modified Delphi method. Consensus was defined as at least 75% agreement among voters. RESULTS: The group agreed that the diagnosis of ulcerative proctitis should be made by ileocolonoscopy and confirmed by histopathology, with the exclusion of infections, drug-induced causes, radiation, trauma, and Crohn's disease. Ulcerative proctitis was defined as macroscopic extent of lesions limited to 15 cm distance from the anal verge in adults. Primary and secondary endpoints were identified to capture response of ulcerative proctitis to therapy. A combined clinical and endoscopic primary endpoint for the evaluation of ulcerative proctitis disease activity was proposed. Secondary endpoints that should be evaluated include endoscopic remission, histologic remission, mucosal healing, histologic endoscopic mucosal improvement, disability, fecal incontinence, urgency, constipation, and health-related quality of life. CONCLUSIONS: In response to the need for guidance on the design of clinical trials in patients with ulcerative proctitis, the Definition and end points for ulcerative PROCtitis in clinical TRIALs consensus provides recommendations on the definition and endpoints for ulcerative proctitis clinical trials.

Weight change after colectomy for ulcerative colitis.

BACKGROUND AND OBJECTIVE: Weight change after colectomy for ulcerative colitis is unknown. The main objective of this study was to describe weight change during surgical management of ulcerative colitis. METHODS: All patients, underwent a subtotal colectomy, then a proctectomy with J ileal pouch anal anastomosis protected by an ileostomy, and finally an ileostomy closure in the context of ulcerative colitis at the Nancy University Hospital from May 2014 to October 2020, were included. For each patient, his healthy weight, preoperative weight and postoperative weight were recorded for each step of surgery. RESULTS: Twenty-six patients were included. The median body mass index of healthy weight was 23.3 kg/m2. Before subtotal colectomy, the median body mass index decreased to 21.3 kg/m2, a reduction of 8.5%. One month after subtotal colectomy, the median body mass index was at its lowest level of 20.8 kg/m2, which represented a 10.7% decrease from the healthy weight. Thereafter a significant increase in body mass index was observed before the proctectomy, reaching the threshold of 22.8 kg/m2, an increase of 8.7% from the lowest level. After the last surgical time, which corresponds to the ileostomy closure, the body mass index was 23.2 kg/m2, this threshold was comparable to the healthy weight body mass index. CONCLUSION: Our study showed for the first time that after colectomy for ulcerative colitis, patients regained their healthy weight, which constitutes a reassuring message for patients before surgery.

New magnetic resonance imaging sequences for fibrosis assessment in Crohn's disease: a pilot study.

BACKGROUND AND OBJECTIVE: Patients with Crohn's disease can develop intestinal strictures, containing various degrees of inflammation and fibrosis. Differentiation of the main component of a structuring lesion is the key for defining the therapeutic management. We evaluated new magnetic resonance imaging sequences (IVIM (Intravoxel Incoherent Motion imaging) and T1 mapping) for assessing fibrosis in Crohn's disease. METHODS: This was a prospective, single-center study of adult patients with Crohn's disease and magnetic resonance imaging examination, including IVIM and T1 mapping sequences, between March 2021 and April 2021. The association between the perfusion fraction (IVIM), reduction of relaxation time between pre- and postcontrast enhancement (T1 mapping), and the degree of fibrosis assessed by a visual analog scale from 0 to 10 was evaluated. RESULTS: A total of 33 patients were included. The perfusion fraction was significantly correlated with fibrosis, with lower perfusion fraction in severe fibrosis (p = .002). T1 mapping sequence was also correlated with the degree of fibrosis, reduction of relaxation time was higher in patients with severe fibrosis than in patients with mild fibrosis (p = .05). CONCLUSION: In Crohn's disease, these new tools could improve the performance of magnetic resonance imaging for transmural fibrosis quantification, and may be useful for improving care.

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.

Inflammatory Bowel Disease and COVID-19 Vaccination: A Patients' Survey.

BACKGROUND: Vaccination against COVID-19 is a major public health challenge, including the community of patients with inflammatory bowel disease. Vaccination coverage is suboptimal in inflammatory bowel disease population. It is of paramount importance to ensure an effective and rapid vaccination program with the adherence of the largest number of well-informed patients. AIMS: We assessed the acceptance of COVID-19 vaccination among inflammatory bowel disease patients. METHODS: We performed a survey as part of routine practice, between January 8th and February 22nd, 2021. All consecutive adult patients followed at Nancy University Hospital for inflammatory bowel disease were included. Patients completed a self-administered, structured, paper-based questionnaire. Demographic data, medical history, knowledge, and perceptions of COVID-19 vaccination were collected. RESULTS: Among the 104 patients who responded to the survey, 57 patients (54.8%) had intent to receive the COVID-19 vaccine. Vaccine efficacy, social responsibility, herd immunity, and desire to return to normal life were associated with self-reported willingness to receive a vaccine (20.2%, 20.2%, 11.5%, and 15.4%, respectively). Unknown long-term safety, risk of adverse reaction to vaccine and concern that the vaccine is being developed too quickly were the most commonly reported reasons for non-uptake (27.9%, 15.4%, and 12.5%, respectively). CONCLUSION: Half of the patients with inflammatory bowel disease would like to be vaccinated against SARS-CoV-2. This rate is similar to that reported in the French general population. Despite some concerns, patients with inflammatory bowel disease understood the necessity to be vaccinated against COVID-19.

Magnetic Resonance Elastography for Assessing Fibrosis in Patients with Crohn's Disease: A Pilot Study.

BACKGROUND: Patients with Crohn's disease can develop intestinal strictures, containing various degrees of inflammation and fibrosis. Differentiation of the main component of a stricturing lesion is the key for defining the therapeutic management. AIMS: We assessed for the first time the accuracy of magnetic resonance elastography in detecting intestinal fibrosis and predicting clinical course in patients with Crohn's disease. METHODS: This was a prospective study of adult patients with Crohn's disease and magnetic resonance imaging examination, including magnetic resonance elastography, between April 2019 and February 2020. The association between the bowel stiffness value and the degree of fibrosis was evaluated. The relationship between the stiffness value and the occurrence of clinical events was also investigated. RESULTS: A total of 69 patients were included. The stiffness value measured by magnetic resonance elastography was correlated with the degree of fibrosis (p < 0.001). A bowel stiffness ≥ 3.57 kPa predicted the occurrence of clinical events with an area under the curve of 0.82 (95% CI 0.71-0.93). Bowel stiffness ≥ 3.57 kPa was associated with an increased risk of clinical events (p < 0.0001). CONCLUSION: In Crohn's disease, magnetic resonance elastography is a reliable tool for detecting intestinal fibrosis and predicting a worse disease outcome.

Prevalence of Self-Reported Venous Thromboembolism and Cardiovascular Risk Factors in Patients with Ulcerative Colitis: The GETAID FOCUS Study.

BACKGROUND AND AIMS: Patients with inflammatory bowel disease have an increased risk of venous thromboembolism (VTE) and cardiovascular disease (CVD). The study aims to determine the prevalence of CVD and VTE risk factors in a large population of patients with ulcerative colitis (UC). METHODS: We conducted a cross-sectional study in 33 French and Belgium referral centers. A questionnaire was developed to explore self-reported risk factors for VTE and CVD, based on the latest international guidelines, in consecutive patients with UC. RESULTS: A total of 1071 patients with UC were included. There were 539 women (50.3%), and the median age of patients was 44 years [32; 57]. The median disease duration was 10 years [6; 17]. In the cohort, 36.5% of patients reported no cardiovascular risk factor (CVRF) and 72% had ≤ 1 CVRF. Regarding cardiovascular risk markers (CVRM) 36.9% of patients reported no CVRM and 78% had ≤ 1 CVRM. Of the 1071 patients, 91.3% of patients reported no VTE strong risk factor and 96% had ≤ 1 VTE moderate risk factor. CONCLUSION: This is the first cohort specifically designed to assess both VTE and CVD risks in patients with UC. More than one third of patients with UC had no CVRF and around three quarters had ≤ 1 CVRF. In addition, more than nine out of ten patients had no VTE strong risk factor and ≤ 1 moderate risk factor. Physicians should be aware of these factors in their patients.

Impact of the Exposome on the Epigenome in Inflammatory Bowel Disease Patients and Animal Models.

Inflammatory bowel diseases (IBD) are chronic inflammatory disorders of the gastrointestinal tract that encompass two main phenotypes, namely Crohn's disease and ulcerative colitis. These conditions occur in genetically predisposed individuals in response to environmental factors. Epigenetics, acting by DNA methylation, post-translational histones modifications or by non-coding RNAs, could explain how the exposome (or all environmental influences over the life course, from conception to death) could influence the gene expression to contribute to intestinal inflammation. We performed a scoping search using Medline to identify all the elements of the exposome that may play a role in intestinal inflammation through epigenetic modifications, as well as the underlying mechanisms. The environmental factors epigenetically influencing the occurrence of intestinal inflammation are the maternal lifestyle (mainly diet, the occurrence of infection during pregnancy and smoking); breastfeeding; microbiota; diet (including a low-fiber diet, high-fat diet and deficiency in micronutrients); smoking habits, vitamin D and drugs (e.g., IBD treatments, antibiotics and probiotics). Influenced by both microbiota and diet, short-chain fatty acids are gut microbiota-derived metabolites resulting from the anaerobic fermentation of non-digestible dietary fibers, playing an epigenetically mediated role in the integrity of the epithelial barrier and in the defense against invading microorganisms. Although the impact of some environmental factors has been identified, the exposome-induced epimutations in IBD remain a largely underexplored field. How these environmental exposures induce epigenetic modifications (in terms of duration, frequency and the timing at which they occur) and how other environmental factors associated with IBD modulate epigenetics deserve to be further investigated.

Real-life pilot study on the impact of the telemedicine platform EasyMICI-MaMICI® on quality of life and quality of care in patients with inflammatory bowel disease.

BACKGROUND: Telemedicine has shown promising results in the follow up of patients with inflammatory bowel disease. This study compared quality of life and disease activity in patients with inflammatory bowel disease monitored using a telemedicine platform versus standard care. METHODS: In this prospective multicenter study, patients with active inflammatory bowel disease were randomized to EasyMICI-MaMICI® telemedicine platform or standard care. The main objective was to assess the efficacy of the software platform, as measured by quality of life and quality of care. Secondary outcomes were changes in the use of healthcare resources, and patient satisfaction in the MaMICI group. RESULTS: Fifty-four patients were enrolled (November 2017-June 2018); 59.3% had Crohn's disease and 40.7% ulcerative colitis. Forty-two patients received biologics at inclusion. After 12 months, a significant improvement in quality of life was observed with MaMICI versus standard care, with mean (standard deviation) changes from baseline of 14.8 (11.8) vs 6.3 (9.7) in the SIBDQ scores and 18.5 (18.7) vs 2.4 (8.3) in the EuroQol 5 D-3L questionnaire scores (both p ≤ .02). Disease activity was similar in both treatment groups. Use of MaMICI slightly reduced healthcare utilization versus controls (mean gastroenterologist consultations 2.2 vs 4.1; p = .1308). Overall satisfaction with MaMICI was high (mean score 7/10), and 46.2% of remaining patients in the MaMICI group continued to use the platform until 12 months. CONCLUSION: Significant improvement in quality of life and overall satisfaction with this telemedicine platform, indicates that further evaluation of EasyMICI-MaMICI in larger numbers of patients with inflammatory bowel disease is warranted.

Defining Magnetic Resonance Imaging Treatment Response and Remission in Crohn's Disease: A Systematic Review.

BACKGROUND: Magnetic resonance imaging is increasingly used to assess treatment response in Crohn's disease clinical trials. We aimed to describe the definition of MRI response and remission as assessed by magnetic resonance enterography [MRE] to evaluate treatment efficacy in these patients. METHODS: Electronic databases were searched up to May 1, 2023. All published studies enrolling patients with inflammatory bowel disease and assessment of treatment efficacy with MRE were eligible for inclusion. RESULTS: Eighteen studies were included. All studies were performed in patients with Crohn's disease. The study period ranged from 2008 to 2023. The majority of studies used endoscopy as the reference standard [61.1%]. MRE response was defined in 11 studies [61.1%]. Five scores and nine different definitions were proposed for MRE response. MRE remission was defined in 12 studies [66.7%]. Three scores and nine different definitions for MRE remission were described. The MaRIA score was the most frequent index used to evaluate MRE response [63.6%] and remission [41.7%]. MRE response was defined as MaRIA score <11 in 63.6% of studies using this index. In 60% of studies using the MaRIA score, MRE remission was defined as MaRIA score <7. In addition, 11 different time points of assessment were reported, ranging from 6 weeks to years. CONCLUSION: In this systematic review, significant heterogeneity in the definition of MRE response and remission evaluated in patients with Crohn's disease was observed. Harmonization of eligibility and outcome criteria for MRE in Crohn's Disease clinical trials is needed.

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).

Difficult-to-treat inflammatory bowel disease: Effectiveness and safety of 4th and 5th lines of treatment.

BACKGROUND: Many patients with inflammatory bowel disease (IBD) have signs or symptoms of active disease despite multiple treatment attempts. This emerging concept is defined as difficult-to-treat IBD. AIM: The objective of this study was to investigate for the first time the treatment persistence, efficacy and safety of biologics or small molecules used in 4th or 5th line therapy. METHODS: We reviewed all consecutive patients with IBD treated at the Nancy University Hospital between July 2022 and April 2023 with the 4th or 5th line treatment for at least three months. The primary outcome was to assess the persistence rate of 4th and 5th line therapy. RESULTS: We enrolled 82 patients with IBD (4th line: 44; 5th line: 38). On Kaplan-Meier analysis, the duration of risankizumab, ustekinumab or vedolizumab therapy did not differ significantly (p > 0.05) as 4th and 5th line treatment. The restricted mean survival time analysis showed that the persistence rate of risankizumab was the highest as 4th line therapy (risankizumab vs. vedolizumab: 36.0 and 29.4 weeks, respectively, p = 0.008; risankizumab vs. ustekinumab: 36.0 and 32.8 weeks, respectively, p = 0.035). In multivariate regression, Crohn's disease diagnosis (Odd ratio 4.6; 95% confidence interval 1.7-12.4) was significantly associated with treatment persistence. CONCLUSION: In this first real-world setting, risankizumab could have a longer persistence rate as 4th line treatment for IBD than other agents. Persistence of biological agents was greater in Crohn's disease than in ulcerative colitis. More studies are needed to compare treatment efficacy in patients with difficult-to-treat IBD.