The Disease Severity Index for Inflammatory Bowel Disease Is a Valid Instrument that Predicts Complicated Disease.

BACKGROUND: The disease severity index (DSI) for inflammatory bowel disease (IBD) combines measures of disease phenotype, inflammatory activity, and patient-reported outcomes. We aimed to validate the DSI and assess its utility in predicting a complicated IBD course. METHODS: A multicenter cohort of adults with IBD was recruited. Intraclass correlation coefficients (ICCs) and weighted Kappa assessed inter-rater reliability. Cronbach's alpha measured internal consistency of DSI items. Spearman's rank correlations compared the DSI with endoscopic indices, symptom indices, quality of life, and disability. A subgroup was followed for 24 months to assess for a complicated IBD course. Area under the receiver operating characteristics curve (AUROC) and multivariable logistic regression assessed the utility of the DSI in predicting disease progression. RESULTS: Three hundred and sixty-nine participants were included (Crohn's disease [CD], n = 230; female, n = 194; mean age, 46 years [SD, 15]; median disease duration, 11 years [interquartile range, 5-21]), of which 171 (CD, n = 99; ulcerative colitis [UC], n = 72) were followed prospectively. The DSI showed inter-rater reliability for CD (ICC 0.93, n = 65) and UC (ICC 0.97, n = 33). The DSI items demonstrated inter-rater agreement (Kappa > 0.4) and internal consistency (CD, α > 0.59; UC, α > 0.75). The DSI was significantly associated with endoscopic activity (CDn=141, r = 0.65, P < .001; UCn=105, r = 0.80, P < .001), symptoms (CDn=159, r = 0.69, P < .001; UCn=132, r = 0.58, P < .001), quality of life (CDn=198, r = -0.59, P < .001; UCn=128, r = -0.68, P < .001), and disability (CDn=83, r = -0.67, P < .001; UCn=52, r = -0.74, P < .001). A DSI of 23 best predicted a complicated IBD course (AUROC = 0.82, P < .001) and was associated with this end point on multivariable analyses (aOR, 9.20; 95% confidence interval, 3.32-25.49). CONCLUSIONS: The DSI reliably encapsulates factors contributing to disease severity and accurately prognosticates the longitudinal IBD course.

This study shows that the disease severity index (DSI) for inflammatory bowel disease (IBD) is a valid and reliable instrument encapsulating the disease phenotype, disease activity, and impact of the disease on the patient; and it accurately predicts for incident disease complications.

Prevalence of and Factors Associated with Respiratory Symptoms Among Patients with Inflammatory Bowel Disease: A Prospective Study.

BACKGROUND: No large, prospective study has investigated respiratory symptoms in patients with inflammatory bowel diseases. We aimed to describe the prevalence of and factors associated with respiratory symptoms in patients with inflammatory bowel disease. METHODS: In an observational, prospective, cross-sectional study, we evaluated the frequency of respiratory symptoms using a validated self-reporting questionnaire from February 2019 to February 2021 during routine follow-up outpatient visits of patients with inflammatory bowel disease followed in the Gastroenterology Department of the Nancy University Hospital. In case of a positive questionnaire, patients were systematically offered a consultation with a pulmonologist in order to investigate a potential underlying respiratory disease. RESULTS: There were 325 patients included, and 180 patients had a positive questionnaire (144 with Crohn's disease). Of the included patients, 165 (50.8%) presented with respiratory symptoms, with dyspnea being the most frequent symptom (102 patients). There were 102 patients (56.7%) who benefited from a consultation in the pulmonology department: 43 (42.2%) were diagnosed with a respiratory disease, mainly asthma (n = 13) or chronic obstructive pulmonary disease (n = 10). Fourteen patients (13.7%) had obstructive sleep apnea. A body mass index increase, being a smoker or ex-smoker, and having articular extra-intestinal manifestations were independently associated with a higher prevalence of respiratory symptoms. CONCLUSIONS: Half of patients with inflammatory bowel disease reported respiratory symptoms in our study. Patients with inflammatory bowel disease should be systematically screened, as pulmonary disease is frequently present in this population, with specific attention being given to smokers or ex-smokers and patients with extra-articular intestinal manifestations.

We conducted a large-scale, prospective study, finding a high prevalence of respiratory symptoms in patients with inflammatory bowel disease, which led to a variety of respiratory diseases, including asthma and obstructive pulmonary disease. Patients should therefore be systematically screened for pulmonary manifestations.

Web-based and machine learning approaches for identification of patient-reported outcomes in inflammatory bowel disease.

BACKGROUND: Messages from an Internet forum are raw material that emerges in a natural setting (i.e., non-induced by a research situation). AIMS: The FLARE-IBD project aimed at using an innovative approach consisting of collecting messages posted by patients in an Internet forum and conducting a machine-learning study (data analysis/language processing) for developing a patient-reported outcome measuring flare in inflammatory bowel disease meeting international requirements. METHODS: We used web-based and machine learning approaches, in the following steps. 1) Web-scraping to collect all available posts in an Internet forum (23 656 messages) and extracting metadata from the forum. 2) Twenty patients were randomly assigned 50 extracted messages; participants indicated whether the message corresponded or not to the flare phenomenon (labeling). If yes, participants were asked to identify excerpts from the text they considered significant flare markers (annotation). 3) The set of annotated messages underwent a vocabulary analysis. RESULTS: The phenomenon of flare was circumscribed with the identification of 20 surrogate flare markers classified into five dimensions with their frequency within extracted labeled data: impact on life, symptoms, extra-intestinal manifestations, drugs and environmental factors. Web-based and machine-learning approaches met international recommendations to inform the content and structure for the development of patient-reported outcomes.

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.

Genomic and molecular alterations in human inflammatory bowel disease-associated colorectal cancer.

Patients with inflammatory bowel disease are at increased risk of colorectal cancer, which has worse prognosis than sporadic colorectal cancer. Until recently, understanding of pathogenesis in inflammatory bowel disease-associated colorectal cancer was restricted to the demonstration of chromosomic/microsatellite instabilities and aneuploidy. The advance of high-throughput sequencing technologies has highlighted the complexity of the pathobiology and revealed recurrently mutated genes involved in the RTK/RAS, PI3K, WNT, and TGFß pathways, leading to potentially new targetable mutations. Moreover, alterations of mitochondrial DNA and the dysregulation of non-coding sequences have also been described, as well as several epigenetic modifications. Although recent studies have brought new insights into pathobiology and raised the prospect of innovative therapeutic approaches, the understanding of colorectal carcinogenesis in inflammatory bowel disease and how it differs from sporadic colorectal cancer remains not fully elucidated. Further studies are required to better understand the pathogenesis and molecular alterations leading to human inflammatory bowel disease-associated colorectal cancer.

Vedolizumab Trough Levels and Histological Healing During Maintenance Therapy in Ulcerative Colitis.

BACKGROUND AND AIMS: Histological healing may be the ultimate therapeutic goal in ulcerative colitis [UC]. We investigated, for the first time, the association between vedolizumab trough levels and histological healing in UC. METHODS: This is a single-centre retrospective cohort study including all consecutive UC patients on vedolizumab maintenance therapy who had a histological evaluation blindly to clinical data and underwent therapeutic drug monitoring, between June 2014 and March 2018. Per-event analysis was performed. Histological healing was defined as a Nancy histological index ≤1. RESULTS: Thirty-five histological samples were analysed. Median [interquartile range] vedolizumab trough levels were higher in the group with histological healing (31.5 [25-49.1] µg/mL) compared with the group without histological healing (15 [9-26.6] µg/mL, p = 0.02). The higher vedolizumab trough level quartiles tended to be associated with greater rates of histological healing [p = 0.10]. A cut-off vedolizumab trough level of 25 µg/mL predicted histological healing with an accuracy of 74% and an area under the receiver operating curve of 0.62 [95% confidence interval 0.58-0.92, p = 0.004]. Bivariate analysis identified a vedolizumab trough level ≥25 µg/mL [p = 0.006], a partial Mayo score ≤1 [p = 0.008], C-reactive protein level <5 mg/L [p = 0.005] and a Mayo endoscopic subscore ≤1 [p = 0.0004] as factors associated with histological healing. CONCLUSIONS: Histological healing was associated with higher vedolizumab trough levels during maintenance therapy in UC. A vedolizumab trough level threshold of 25 µg/mL proved most optimal to predict histological healing according to the Nancy histological index. Confirmation of these data in larger, independent cohorts is needed.

Treatment Persistence of Infliximab Versus Adalimumab in Ulcerative Colitis: A 16-Year Single-Center Experience.

BACKGROUND: Infliximab and adalimumab are widely used in the treatment of patients with ulcerative colitis (UC). There are few published data on the treatment persistence of infliximab and adalimumab in patients with UC. METHODS: We aimed to compare the treatment persistence rates of infliximab versus adalimumab as first- and second-line tumor necrosis factor antagonists (anti-TNF), to identify factors potentially associated with persistence, and to evaluate reasons for withdrawal in UC patients. We performed a retrospective, single-center cohort study of UC patients treated with infliximab or adalimumab for at least 6 months between June 2002 and May 2018. RESULTS: The median (interquartile range [IQR]) duration of follow-up was 5.4 (3.2-8.3) years. For first-line anti-TNF agent, data on 160 patients with UC were analyzed. The mean (SD) duration of persistence was 3.4 (3.5) years and 2.1 (2.0) years in the infliximab and adalimumab subgroups, respectively (P = 0.24). Concomitant use of 5-aminosalicylate was associated with higher persistence of first-line anti-TNF treatment in the overall population (hazard ratio [HR] 0.5; 95% CI, 0.3-0.8; P = 0.002). For second-line anti-TNF agent, data on 43 patients were analyzed. The mean (SD) duration of persistence was 2.0 (1.7) years and 3.2 (3.1) years in the infliximab and adalimumab subgroups, respectively (P = 0.95). No factors were associated with persistence of second-line anti-TNF treatment. CONCLUSIONS: Infliximab and adalimumab showed similar levels of persistence as first- and second-line anti-TNF treatments. Concomitant use of 5-aminosalicylates was associated with higher persistence of first-line anti-TNF treatment.