Background A clinical decision support tool (CDST) has been developed and validated for predicting outcomes of vedolizumab (VDZ) therapy for patients with Crohn’s disease (CD) and ulcerative colitis (UC), respectively. We aimed to validate each CDST for predicting outcomes and need for drug optimisation in patients with inflammatory bowel disease (IBD). Methods We retrospectively analysed 166 patients with IBD (71 with CD, and 95 with UC) treated with VDZ from January 2017 through November 2021 at 6 tertiary referral centres in Korea. We assessed clinical remission (CREM) and response (CRES), corticosteroid-free clinical remission (CfCREM) and response (CfCRES), biochemical response (BioRES), endoscopic healing (EH), and need for drug optimisation by CDST-defined response groups (low vs. intermediate to high probability group with a cut-off of 13 points in CD, Table 1A, and 26 points in UC, Table 2A, respectively). CDST was evaluated by area under the receiver operating characteristics curve (AUC) and test performance. Results Patients were classified as low (27 with CD, and 28 with UC) and intermediate to high probability group (44 with CD, and 67 with UC). Among CD patients, there showed no significant difference in the response rate of any outcomes between CDST-defined groups. Among UC patients, the rates of CREM (41.0 vs. 18.5%, p=0.040) and EH (56.5 vs. 33.3%, p=0.045) at week 14 were higher among intermediate to high probability group. The rate of drug optimisation during maintenance therapy was also higher in low probability group (54.2 vs. 30.2%, p=0.038). At week 26, CDST for CD discriminated CfCREM with an AUC of 0.656 (sensitivity 87.5%, specificity 43.8%) (Table 1B). Meanwhile, CDST for UC identified CREM with an AUC of 0.606 (sensitivity 83.3%, specificity 37.9%) at week 14 (Table 2B). BioRES of FC was identified with an AUC of 0.649 (sensitivity 84.6%, specificity 45.2%) at week 26. BioRES of CRP was identified with an AUC of 0.660 (sensitivity 68.8%, specificity 63.2%) at week 26, and with an AUC of 0.642 (sensitivity 70.0%, specificity 58.3%) at week 54. Drug optimisation during maintenance therapy was identified with an AUC of 0.620 (sensitivity 54.2%, specificity 69.8%). Conclusion Both CDST for CD and UC can be used to help guide VDZ therapy for Korean patients to predict BioRES with a fair discriminant function and moderate sensitivity.

Background We aimed to compare trough infliximab levels and the development of anti-drug antibody (ADA) for 1 year between Crohn’s disease (CD) and ulcerative colitis (UC) patients who were biologic-naïve and to evaluate their impact on clinical outcomes. Methods This was a prospective, multi-center, observational study. Biologic-naïve patients with moderate to severe CD and UC who started CT-P13 therapy were eligible for the study. The trough drug and ADA levels were measured serially for 1-year after CT-P13 initiation. Clinical outcomes were assessed with intention-to-treat purpose. Results 267 patients who received CT-P13 treatment were enrolled in the study (CD 168, UC 99). The rates of clinical remission (72% vs. 32.3%, p<0.001) and clinical response (75.6% vs. 47.5%, p<0.001) at 54-week were significantly higher in CD than in UC. The median trough drug level (μg/mL) was significantly higher in CD than in UC up to 14-week (2-week, 19 vs. 15, p<0.001; 6-week, 13 vs. 9, p<0.001; 14-week, 3 vs. 2, p=0.001, Fig 1). The median ADA level (AU/mL) was significantly lower in CD than in UC at 2-week (6 vs. 7, p=0.046), 30-week (8 vs. 12, p=0.007) and 54-week (9 vs. 12, p=0.032, Fig 1). The difference in drug and ADA levels between CD and UC remained significant after adjustment for confounders in repeated measures analysis. Cox proportional hazard analysis showed that CD over UC (adjusted hazard ratio (aHR) 0.78, 95% confidence interval (CI) 0.62–0.95, p=0.016, Fig 2) and no immunomodulator (aHR 1.55, 95% CI 1.07–2.25, p=0.02) were independent risk factors for the development of ADA. The development of ADA at 2-week (adjusted odds ratio (aOR) 0.12, 95% CI 0.03–0.6, p=0.009) and CD over UC (aOR 1.85, 95% CI 1.33–2.56, p=0.0002) were independent predictors of clinical remission at 54-week. Conclusion CD shows favorable pharmacokinetics of infliximab including high trough drug and low ADA level compared with UC which might be related with better clinical outcomes for 1-year of infliximab.

Background Biologics such as infliximab is the main treatment for steroid refractory acute severe ulcerative colitis (ASUC), However, there are only a few studies on the effectiveness and safety of biologics in steroid refractory ASUC. In this study, we evaluated the effectiveness and safety of biologics as a rescue therapy for biologics naïve steroid refractory ASUC patient in Korea. Methods We retrospectively included patients who were hospitalized at seven tertiary medical centers for ASUC management between January 2015 to December 2020, and data on the demographic and clinical variables, disease activity, treatment method, treatment response, adverse event, readmission due to any reasons were checked Results A total of 230 ASUC patients were included, of which 220 were biologic naïve patient. The response rate of steroid in these patients was 74%, and infliximab was administered as rescue therapy to 53 patients who failed initial steroid treatment. The response rate to infliximab as rescue therapy was 96%, and 2 patients who did not respond received colectomy. One of the two patients who underwent colectomy died of sepsis. There was no infliximab-related adverse event during hospitalization. Although infliximab itself was not a factor associated with infection after discharge (10% vs. 16%, p=0.355), combination therapy with thiopurine was a risk factor for infection after discharge. (Odd ratio 7.302, 95% CI 2.101-25.372, p=0.002). A total of 12 infections occurred in patients treated with infliximab after discharge (3 pneumonia, 1 skin infection, 3 cytomegalovirus colitis, 4 Clostridium difficile infection) and were associated with readmission. (40.1% vs. 75%, p=0.031) Conclusion As a rescue therapy in biologics naive steroid refractory ASUC, infliximab showed a 96% therapeutic response. Although infliximab itself did not increase the risk of infection after discharge, the combination with thiopurine increased the risk of infection after discharge

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.

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