Background The aim of this study to assess the efficacy and safety of adalimumab (ADA), a monoclonal antibody against tumour necrosis factor α (TNF-α), and to explore predictors of response in Korean patients with ulcerative colitis (UC). Methods We conducted a prospective observational multicenter study over 56 weeks in adult patients with moderately to severely active UC. Clinical response and remission were assessed by Mayo score. Mucosal healing was defined as Mayo subscore 0 or 1. Faecal calprotectin (FC) were assessed at baseline, week 8 and 56. Adalimumab drug levels were checked at week 8 and at loss of response. Missing or incomplete data were handled using the nonresponder imputation method. Results A total of 146 patients were enrolled and included in the analysis. Clinical response rates were 52.1% (76/146) and 37.7% (55/146) at week 8 and 56, respectively. Clinical remission was achieved in 24.0% (35/146) and 21.9% (32/146) of patients at week 8 and 56. Steroid-free remission rates were 21.2% (31/146) at week 56. Mucosal healing rates were 39.0% (57/146) and 30.1% (44/146) at week 8 and 56. Prior use of anti-TNF-α did not affect the clinical and endoscopic responses. Treatment persistence was achieved in 57.5% (84/146) of patients at week 56. Adalimumab drug level was significantly higher in patients with clinical response (10.8 vs. 8.0, p = 0.004), clinical remission (11.7 vs. 8.8, p = 0.007) and mucosal healing (11.0 vs. 8.5, p = 0.010) at week 8. Adalimumab dose was escalated to 40 mg weekly in 25 (17.1%) patients, and clinical response and remission were achieved in 40% and 20% of patients at week 56, respectively. Mean faecal calprotectin levels were significantly more decreased in clinical responders compared with non-responders at week 8 (336.3 mg/kg vs. 628.8 mg/kg, p < 0.001). The Fecal calprotectin levels are well correlated with endoscopic severity, and the best cut-off value to predict mucosal healing was 274 mg/kg. The lower endoscopic severity, higher body mass index and higher serum albumin level at baseline were associated with a clinical response at week 8. The lower Mayo score, lower C-reactive protein level, clinical response (74.5% vs. 38.5%, p < 0.001) and mucosal healing (52.7% vs. 30.8%, p = 0.008) at week 8 were associated with clinical response at week 56. Serious adverse drug reactions were identified in 2.7% (4/146) of patients including 1 case of pulmonary tuberculosis. Conclusion Adalimumab is safe and effective for induction and maintenance in Korean patients with UC, regardless of prior anti-TNF therapy. Adalimumab drug level is associated with the efficacy of induction therapy. A better response to induction therapy can predict a better long-term response.

Background Intravenous steroid therapy is the main initial treatment for acute severe ulcerative colitis (ASUC). However, steroid dependence in patients who were treated with intravenous steroid therapy for ASUC is not fully evaluated. We aimed to determine the prevalence and risk factors of corticosteroid dependence after treatment of ASUC. Methods Adult patients who were admitted for the treatment of ASUC satisfying Truelove-Witts criteria from January 2015 to December 2020 were included in the study. Steroid dependence was defined as a failure to taper steroids below 10 mg within 3 months from initiating intravenous therapy or relapse within 3 months after steroid discontinuation. Results Among a total of 140 patients who received intravenous steroids as initial treatment for ASUC, 105 (75.0%) showed a response while 35 (25.0%) were refractory to steroids. Of 105 patients who responded to intravenous steroid therapy, 21 (20.0%) showed steroid dependence during the follow-period. Demographic and clinical variables were not significantly different between steroid-dependent and steroid response groups. However, initial C-reactive protein (CRP) levels in steroid-dependent groups were numerically lower compared with those in the steroid response group with statistical significance (4.4 ± 4.6 mg/dL versus 7.0 ± 6.4 mg/dL, p = 0.04). Conclusion A total of 20.0% of responders to intravenous steroid treatment for ASUC had a steroid dependency during follow-up. The demographic and clinical features of ASUC according to the presence or absence of steroid dependency were similar. Initial CRP levels were low in patients with steroid dependence.

Background Many patients with inflammatory bowel disease experience extra-intestinal manifestations (EIM)s. The presence of EIMs is related to disease activity. Acute severe ulcerative colitis (ASUC) is associated with a high inflammatory burden. However, there are insufficient studies on the relation between the presence of EIMs and the prognosis of exacerbation of ulcerative colitis. This study was conducted to elucidate the correlation between EIMs and ASUC. Methods We retrospectively included patients who were hospitalized at four tertiary medical centers for ASUC management between January 2015 to December 2020, and data on the underlying disease, disease activity, EIMs, colectomy, treatment method, and readmission due to ulcerative colitis aggravation were checked. Results A total of 145 patients (mean age 44.4 years, 68 women) were investigated. The initial partial Mayo score, the Mayo endoscopy sub-score, and the ulcerative colitis endoscopic severity index were 7.6±0.8%, 2.7±0.5, and 6.0±1.4%, respectively. EIMs were expressed in a total of 10.3% (15/145) of patients. The most common type of EIMs was the peripheral articular type (46.7%) followed by skin lesions (20%) and axial articular disease (13.3%). The group with EIMs was younger and had a higher proportion of women than the group without EIMs (39.4 versus 45 years, p=0.03), and had a longer duration of disease (5.8 versus 3.5 years, p=0.02). The Mayo endoscopic sub-score (2.9 vs. 2.7, p<0.01) and partial endoscopic score (7.9 vs. 7.6, p<0.01) were also higher in the EIMs group. The length of hospital stay was also longer in the EIMs group (25.5 days vs. 13.8 days, p<0.01). The response rate to initial treatment was lower in the EIMs group (71.4% vs. 95.5%, p<0.01), and more rescue therapy (28.6% vs. 4.5%, p<0.01) was performed. The rate of colectomy on admission was also higher in the group with EIMs (13.3% vs. 0.8%, p<0.01). Patients with EIMs showed a high tendency to visit the hospital for re-exacerbation of ulcerative colitis after discharge (p=0.07, HR 2.10 CI: 0.93 – 4.76). Conclusion EIMs were expressed in a total of 10.3% of patients with ASUC. The presence of EIMs suggested a poor prognosis in ASUC.

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Background Tumor necrosis factor (TNF) antagonists are recommended for patients with ulcerative colitis (UC) for the effectiveness in inducing and maintaining clinical remission. We investigated the altered fecal metabolites and lipids by anti-TNF treatment and prediction model of remission in patients with UC. Methods A prospective, observational multicenter study was conducted at 17 academic hospitals in Korea. Fecal samples were collected from adult patients with moderately to severely active UC (n=116) before and after 8 and 56 weeks of adalimumab treatment and from healthy controls (HC, n=37). Clinical remission was assessed using Mayo score. Metabolome and lipidome analyses were performed using gas chromatography-, and nano electro spray ionization-mass spectrometry, respectively. Prediction models of remission were developed using baseline fecal samples by Fourier transform-infrared (FT-IR) spectroscopy combined with machine learning algorithms. Results Fecal metabolites and lipids in UC were different from HC at baseline and were changed similarly to HC during treatment. Fecal metabolites and lipids in remitters (RM) after treatment were more grouped and clustered with those of HC compared with non-remitters (NRM). In RM, 2-aminobutyric acid, galactose and dodecanoate levels which were previously decreased at baseline compared to HC increased to the levels of HC, whereas benzoate, stigmasterol, 3-hydroxybutyrate, diacylglycerol and triacylglycerol levels which were previously increased at baseline compared to HC decreased to the levels of HC after 56 weeks of treatment. The best model predicting short-term remission was developed by applying logistic regression (LR) and radial basis functions (rbf) support vector machine (SVM) with an accuracy of 0.99 (95% confidence interval [CI], 0.98–1.01). For long-term remission, the best prediction model was developed by rbf-SVM revealing 0.99 [CI 0.98–1.01]. LR and K-nearest neighbors also showed excellent performance for prediction of long-term remission (accuracy of 0.96 [CI 0.90–1.02] and 0.96 [CI 0.92–1.00], respectively. Conclusion Fecal characteristics in UC were changed after anti-TNF treatment and became similar to those of HC. Potential therapeutic target compounds were suggested to develop novel therapeutic strategies for UC. Novel remission prediction models by FT-IR spectroscopy were also established.